1 REENING FOR A DROGEN DEPRIV TION THER PY RELATED SIDE EFFE T I MEN WITH PRO T T AN ER by Virginia Da i B . c ., ni v r it y fW e tern ntari , 200 7 PR F N R ING: FAMILY PRA TITIONER UNIV RSITY OF NORTH RN BRIT! H October 20 15 © Virginia Davis, 20 15 L MBI 2 A b tract ndr gen d privation th rap y ( T) i a c 1nm n meth d f tr atm nt D r pr tate cancer. There ar a ari ty of id e eft ct a ciated with it u e that an nega ti ely impa t h alth and qu ality of lit i t in th lit rature ar und y t a ignificant gap rec 1nmend ation . a re ult, thi pr j ect (NP ) practi cing in a primary care ti n: r N ur Prac titioner tting, what creenin g i requi r d t id entify id eft c t in men with pro tate cancer receiving data related to k t an wer the qu mpr h n ive creenmg DT and m en with pr T. li gibility criteri a fi r thi literature review includ ed tate cancer, with no limitati n t ag r tage of di ea e. T he m ajo rity of the parti cipant in the primary tudi e includ ed at least one tud y group receiving ADT in the primary care ettin g. Thi review pre ented findin g ba ed o n th ph y ical cognitive and p ychological ide ffec t f ADT, fi !lowed by a de cripti on of clini cal practi ce guidelines, clinical review and editori al in ord er to highli ght the ga p in creening reco1nmend ations. Through this proce , recommend ation fo r the creenin g of each indi vidu al ide effect were developed. It was detem1ined that patient should und ergo fo ll ow- up within 3 months of ADT initi ati on, fo llowed by every 3-6 months. Limitations of thi s project incl ud e a scarcity of studi es on pecific side effects. Implica ti on fo r practice includ e patient and primary care provider (P P) education as well as the development of comprehen ive gui deli ne . Moreover, further research is required fo r newly defined sid e effect . It i through appropriate screening that ADT related sid e effect are id entifi ed and treated, thu limiting their impact on health and qu ality of life. 3 Acknowledgment I would like to thank my up rvi ry co1runitt e inda Van P lt, M eN NP-F and Janet Baillies, M eN NP-F for their invaluable directi n and upport in h lping me to compl et thi project. I would al o like to thank my family and friends forth ir patience, upport and encouragement throughout my graduate tudie . 4 TABLE OF CONTENT Ab tract 2 Acknow I dgment 3 Table of ontent 4 Glo ary 6 Introduction 9 12 Background and ontext Pro tate Cancer in Primary Care The rol e of the ur e Practitioner Prostate ancer Incid ence Prostate ancer Anatomy and Pathophysiology Prostate ancer Treatments Androgen D epriva tion therapy Side Effects of Androgen D eprivation th erapy Physical side effects Cognitive side effects Psycholo gical side effects 20 26 26 Chapter Two Research M ethods 29 Chapter Three Findings Physica l side effects of androgen deprivation therapy Cognitive side effects of androgen deprivation therapy Psychological side effects of androgen deprivatio n therapy Clinical Practice Guidelines Clinical Reviews ditorial 33 Chapter ne hapter Four Di scu sion lini cal Prac ti ce Recommendation ununary of Clinical Practice Recon11nendations Recommendations for du cation ReconllTiendations for Research Summary and conclu ion 12 13 14 16 17 19 33 43 45 49 54 59 61 61 0 1 3 4 5 Reference Appendix A: Pharmacol gical 86 ndrogen Depriva tion Th rap y Appendix B: Literature earch Flow hart 97 99 6 Glo ary Androgen are mal h rm n ciety 2014 ). primarily te t tero ne and dih ydr t t r ne ( m n can ancer Andropau e g nerally ccur in m n betw e nth ag f 45 and 55 in which te t terone level fall leading to redu e xual dri and vig ur (andr pau e, 20 15) . ltem atively call ed mal e m enopau (andr pau , 20 15) . Anorgasmia i the inability to achieve rga m (lntemati nal ociety [! r exual M di cine, 2015). Anti-a ndrogen area l o kn wn a andr gen bi ynthe i . They work by inhibiting adrenal and intra-tumour production of te to terone. amp ] in K etoco naz le and yr t r on (Locke & lliot, 20 15). Astheni a i characteri zed by g n rali zed weakne fatigue (Bruera & MacDonald, 19 ). and can al o include ph y ical and m ental Brach yth erap y is a typ of cancer treatment that refe rs to th e placem nt of radioactive 'seed ' into the body, either inside or nex t to a tumour. The eeds deli ver radiation to th cancerou tumor while minimizing the unounding ti s ues ex po ure to radiation. Thi m ethod of radiation therapy i co mmonly u eel for pro tate cancer, which is call ed Tran perineal Implantati on of the Prostate (TPIP) . During TPIP radioa ctive seed are inset1ed into the pro tate und er general anesthesia (Briti h Columbia Cancer Agency [BC ], 20 14a) . C ryoth erapy is a form of pro state cancer trea tment that freezes and de troy prostate cancer cell s (National Cancer In titute [NCI], 20 15) . E rectil e dysfun ction is defined as the persistent inability to achieve or maintain an erection (Buttaro, Trybulski, Polga r Bailey, & and berg- ook, 20 13 ). Extern al bea m radiation is the use of hi gh energy ray to kill or hrink malignant tumour cell (B A, 20 14a). FRAX is a fracture ri k a essment tool developed from th e World H ealth rganization . Th tool incorporates individual patient ri k factors in combination with bone mineral den ity re ult llaborating entre for and gives a 10 year probability of fracture (World Health rganization Metabolic Bone Disea e, n.d .). Gynecomastia i deGned a the benign enlargement of the male brea t and i th e rc. ult of proliferation of ductular element of the brea t (Buttaro et al., 201 ). 7 Gonad otropin relea in g hormon e (GnRH) i a ynth tic an al g f Jut iniz ing h rm n relea ing h rm n ag ni t (LHRH) with nti all y th am e m ch ani m f ac ti on (B 20 12a). H emoglobin i a lab rat ry te t that d t rmine the t ta l am unt f hem gl bin in the b1 d. ygen and arbon di x id H m gl bin it lf a t a a v hi 1 [! r th tran p rtati n f throu gh ut th b dy. T he te t i an imp rtant part f the c mplete bl d cell count ( B ) and can be h elpfu l in va lu ating [! r an m ia (Pagana & Pagana, 201 ). H emoglobin Al or gly ylat d h m gl bin i a m ea urem ent u d c mm n ly in di abetic pati ent fi r di agno i and t m onit r r p n e t trea tm ent (Pagana & Pagana 20 l ). The va lue refl ect an average bl d glue e lev I in the bl d ver a 100 t 120 day pan (Paga na & Pagan a 20 13). Hi gh density lipoprotein (HD L) i o ft n r fe rred t a 'g od cho le ter I' a it is re p n ib le fo r co li ctin g cho l t ro l from th b dy' ti u and end oth e lium and returnin g itt th e li ve r. Removal of chole terol from the ti ue and end othelium p rov id e prot c ti n aga in t heart di ea e (Pagan a & Pagan a 20 13) . Hypogonadi sm occurs when ex gland , uch a th e te tes in m en and ovari e m wom en produ ce reduced or ab ent am ount of ex hormone (M aJiel, 20 12) . Impotence refer to the inability to achieve or m aintain an erection ( ilverb erg, 20 15). In sulin resistance i th e "de reased en iti v ity of ti s ue to g luco e uptake w ith no rm al concentrati ons of in ulin'' (Buttaro et al. , 20 13, p . 1062). L ibido is ones sexual drive or in tinct (libido, 20 15) . Low density lipoprotein (LD L) i part of the lipid profi le. LD L catTies ch olesterol from the liver to di ffere nt ce ll s in the body. LDL is often re~ rr d to as 'bad cho le tero l' (Paga na & Pagana, 20 13). Luteinizin g hormon e releasing hormon e agoni st (LHRH) are medica ti on u ed for pro tate cancer. Mechanism of action i the over timul ation of the hypothalamu -pitu itary-adrenal te te. axis whi ch stops the production of te tostero ne. xa mpl e includ e serelin and Leuprolide (Locke & lliot, 20 15). Mea n corpu scular volum e (M V) refers to the vo lume or ize of a ingl red blood cell. Its meas urement i comm only used to help classify anemi a (Pagana & Pagana, 2013 ). Metasta i i th e term used to de crib when cancer cell pread from it · original (primar ) locatio n to anoth er area in the body. When this oc ur th e ancer c ntinuc to grow in it new loca tio n ( anad ian ancer o icty, 20 14a) . 8 Neo-adjuvant re£ r t cancer treatment that i giv n prior to the m ain tr atment pre crib ed (N I, n.d.). Orchi ectomy i th urgi al r moval of the te tiel ( anadi an ancer ciety 20 14a). Osteopenia refer to abnonn al (low) bon den ity, but n t as low a b ne density in the o teop rotic rang (K araguz 1 & H lick, 20 10). Osteoporosis i a di ea e in which bone b com e m ore fragil e with increa ed susc ptibility for fractur (Buttaro et al. , 20 1 ). Pro tate pecifi c Anti ge n (PSA) i an enzym e re l a d by the pro tate gland . Levels can be elevated related to both beni gn and malignant conditi n . A norm al P A level i under 4 ng/mL. Level can be m ea ured w ith a erum laboratory te t (Buttaro et al. , 20 13). Psychometrician i a p ychologi t w ho i skill ed in administering and interpretin g psychological test (P ychim trician, 20 15). Quali ty of life definiti ons can vary widely. The W orld H ealth Organiza ti on (1997) defin es quality of life as an " indi vidu a l' s percepti on of th ir pos iti on in I ife in th e co ntext of th e c ultur and value system s in which they live and in relation to their goal , ex p ctations, stand ard , and concerns. It is a broad rangin g co ncept affected in a co mpl ex way by the perso n's ph y ica l health, psychological state, level of indep endence, social relati o n hip , p er onal beliefs and their relation hip to salient fea tures of their env ironm ent" (p. 1) . Radical prostatectom y is a surgical procedure done fo r locali zed prostate cancer (BC A, 20 14b ). The surgery invo lves removing and sampling pelvic lymph nodes, and if negative for m alignancy, the rem oval of the prostate gland and seminal vesicle (BCCA, 20 14b ). Conlffion side effects includ e incontinence and erectile dys function (BCCA, 20 14b ). Testosterone is a honnone which is primaril y produced in the testes, with small amounts produ ced in the ovari es and adrenal cm1ex. This hormone is primari ly responsibl e fo r the development of m ale secondary sexual characteristi cs (Testosterone, 20 15). Triacylglycerol also refers to triglycerides, which are naturall y occmTing fatty acid and glycero l found in oil and fats (Triacylglycerol 20 15). Very low density lipop rotein (VLDL) is another laboratory co mponent of the lipid profile. VLDL canie triacylglyceroJ fro m the liver to adipose ti sue in th e body (Pagana & Pagana, 20 13) . 9 Introduction The diagn f anc r can b a life-al t ring event. impact phy ical c gnitive and p ych th cane rand it treatment can gical function all of which can influenc elf- teem; intimate and ocial r lation hip ; and o erall health and quality f liD Pro tat cancer i th 0 econd mo t comm nly dia gn d cancer in men w rldwid e ( adro & Con equently with uch ignifi ant pre al nee rat (P P ), uch a Nur the likelih d that primary care provider Practiti n r ( P ) will be in v lved with th e dia gn of this di ea e is ubstantial. Moreover, ex ten ive progre in pr arzotto, 2011 )0 i and managem nt tate cancer trea tm nt have extend d life xp ctancy, meaning pati ent are living longer with th e di ea e and obtaining care and treatment by P P in the conununitie in which th ey live (In titute of Medi cine, 2008) 0 aturally, the level of interacti n between P P and pati ent depends on the method of treatment and ymptomology related to b th cancer and treatm ent 0 For exampl e, androgen deprivation therapy (ADT) , which i a form of honnone th erap y, i commonly pre crib ed by specialists but administered and managed by PCPso ADT is the most co1nmon m ethod of treatment for prostate cancer, with estimations that at lea t 50% of patients with pro tate cancer will be treated with ADT at orne point in their illness (Mohile, Mustian, Bylow, Hall, & Dale, 2009; Tadros & Garzotto, 20 1 1)0 ADT redu ces te to teron e to ca trate levels that inhibits or slow the growth of hormone dependent cancer c 11 (Mazzola & Mulhall, 2012)0 Androgen deprivation is achieved through suppre ing th e production of androge n by the te te , which produce 90-95% of th e body' total androgen, or by blocking th e effect of androgen at androgen receptor (Mazzola & Mulhall, 20 12)0 With the reduction of te to terone comes a vari ty of arly and lat ide efT ct , a well a an increa ed ri k for th r health condition such a cardio a ular di case, diabet s, 10 te p ro i and functi nal d line. Furthermore, th e literature ha dem n trated that verall tho e with ancer die f non-ca n (Br wn tal. , 200 a c ited in ignifi cantly wor ingla, owan, tull tal. , 2007). quality f life with chang anoll, at a much hi gher rat than the general publi c r r lated ca u inally, th e trea t d with DT dem n trat t both m ntal and em ti nal well-b in g ( ary, perberg, 20 14; va n nd el & Kurth, 200 ). Thi hi ghli ght the nece ity t acknowledge th 1 ng t nn health and p ychol gical cqu la e a ciat d with ADT and the ub equent need t co n id er creenin g and identificati n o f id e effect in rder t commence appropriate trea tm ent. Primary care provider , uch a N P , are oft n the fir t and m t frequ nt p int of co ntact for patient when acce ing car with c ntinu d re ponsibility ~ r providing pati ent care for a variety of health probl em (Ameri can cadem y f Famil y Ph y ician , 20 15; Heal th F rc ntario, 20 13). Thi ongo ing e tabli hed relati on hip between patient and P P i pivo tal for the id entification of ADT related si de effect to en ure trea tm en t i provided to maximize hea lth and quality of life during thi treatment. However, an important con ideration for providing thi complex peciality care i availability and knowledge of up to date re ources and t ol . ntil recently, the focu of prostate cancer re earch ha been largely focu ed on treatment and achieving long-term surviva l. A a result, the literature illustrate an ab und ance of data regarding the effectiveness of ADT and its as ociated side effect , however pecific recommendation or practice guidelines for the eva lu ation of ide effect are par e (Mclnto h et al., 2009) . imilarl , alth ugh ri ks of developing additional health condition related to DT are docum ntcd in the literature, guidelines related to creening for the e health conditi n are not w II defined or c mprehcn ive. n equently, P P have little evid n e to guide care with regard · tom 'thod · and frequ ncy fa e mcnt [I r tho c rccci ing D . Without c mprchcnsi\ e guid ~ Jin ' S r 'a dil ~ 11 availabl e, P P will hav limited aw ar ne f the ub tantial impac t f DT on health related quality of life and appropriat tr atm nt of id e effect cannot be adequ ately pr vid d . Furthermore, the literatur ha identified gap in are w ith rega rd to ~ 11 w up and screenin g for ide effect in tho e recei mg DT d m on trating a furth r need. The obj ctive of thi integrati ve literature review i t an wer the followin g qu e tion : or NP practi cing in a primary care etting, what creening i requir d t id entify ide effect in m en with pro tate cancer rec i ing primary care, the role of the DT. The rev iew will begin by de cribing pr tate cancer in P a a P P, pro tat cancer incid ence a well a pro tate anatomy and pathophy iology. Pro tate cancer treatment , Nex t, the literature earch proce DT and it id e ffect w ill then be di scu sed . wi ll be de crib ed. indin g fro m th e integrati v review will then be pre ented followed by implicati n and reconun end ati on fo r prim ary care practi ce, educati on and re earch. 12 hapter ne Background and Pro tate ancer in Primary are Primary care i central to the di agn cit d in Allgar & ontext i and m anagem ent f cancer ( utrunert n, 2000 a eil , 200 5). Primary are ften re fer t a pati nt' fir t co nta t for medi ca l care, in whi ch P P , uch a n ral Pra titi ner and P , a um re p n ibi lity [! r continuou , comprehen iv and c - rdinat d care ( tarfi eld , 1994 as cited in 2005 ). Primary car inc lud eil health prom tion, di ea e preventi n, health m aintenance, coun eling, patient du cation, di agno i and trea tm nt of illne specialty care (Ameri can llgar & cad emy of Famil y Phy ic ian , 20 15). a w ell a facilitating acce s to s a re ult, P Ps provid e a fo cal point for continuou s health care and thu are generall y invol ved in care pri or to dia gnosi and have a well-e tablished relation hip and role in ongoing care (Department of H ealth, 2000 a cited in Allgar & N eil, 2005 ). Although traditionall y health care managem ent of tho eon acti v treatment for cancer ha been limited to sp eciali st and outpati ent oncology clini c , care for tho e receiving hormonal treatment regimens uch as A DT has now hifted to the PCP . Thus, P Ps have increasing respon ibility for greater a pect of cancer care, uch as fo ll ow up , a se m ent and managem ent of side effects and co-m orbiditi e , and for ambulatory treatment in the community (Al lga r & N ea l, 200 5). Additi ona ll y, with ADT' demo n trated imp rove ment 111 longevity of life, pati ents are li ving longer with per i tent di ea e that crea te additi onal con iderati ons for P Ps in regards to incorporating appropri ate crcenin g for both di ea e and trea tm ent related sid e effects. The Rol e of the N ur e Pra ctition ea· N ur practiti ner (N P ) are autono mou h alth care providers . Ps ha e und rgraduate 13 educati nand exp ri ence in nur ing, with additi nal Ma ter or PhD level educa ti n from aero h alth di ciplin , including m di in e. P' brin g t g ther th medi ca l knowledg required of a P P, uch a th ability t diagn e di ea e and conditi n , rd r di agn tic te t and pre crib and manage medication and treatment , with the valu e and ki ll of the nur ing pr fe i n ( anadian ur e A ociation, 20 11 ). Mor health promotion, illne s preventi n, di agn ver, P' pr vid e direct pati ent are, addressing i and treatm ent f acut and chr nic illne the cope of a holi tic nur ing per pective ( anadi an Regi tercd [CRNB ], 20 15a). ince incepti n f the ro le in NP' role in the anadian h alth ca r demon trating "tim ely acce ur e of Briti h within olumbia anada in th e earl y 1960' , th e va lu e of the y t m ha been identified bynum r u tudie , to indi viduali ed, hi gh qua lity, co t effective ca re" ( anadian Nur e A ociati n, 20 I I , para . I 0). Although P' are current ly restricted in pre cribin g ADT, the NP's role as a PCP erve a a co ntinu ou foca l point for managing patients throughout the cancer trajectory. Thus, throughout cancer treatment patient will continue to access care in which NP's can provide competent assessments, upport, educa ti on and counselling with regard to diagnoses, manage ment and therapeutic interve nti ons. Additionally, NP's ca n perform any appropriate screening and diagnostic invc ti gati ons required for cancer and it treatments u ing standardized tools, laboratory and diagnostic imaging (CRNB , 20 15b ). Prostate Cancer Incidence In an ada, prostate cancer i the most common type of cancer diagno ed in men, accounting for 24% of all new cancer diagno e in men in 2014 ( anadian ancer ociety, 20 14a). Similarly, prostate cancer is the mo t frequ ntly diagno ed cancer in men in Briti h lumbia, with approximately 3600 men diagnos d in 2014, and over 25 000 men tlu·oughout anada in 20 ll ( anadian an er ciety, 20 l4b; Venkate waran, Margel, Yap, H rsc , Yip, · 14 Fie hner, 20 12) . De pi te the high incidence, du t th natur f th di ea a well a the developm nt of ucc ssfu l treatment modalitie motiality rates are relatively low . Fiv year relative urvival rate remain high at 96%, with an verall death rate f 17 men for every 100,000 people ( anadian anc r oci ty, 20 14a). The avera g ag f dia gn i i 79 years old , with ov r 70% of case in men over the ag of 65 year old (Mohile et al. 2009) . Anatomy and Pathophy iology The pro tate i a mall gland D und in men pati of both the male urinary and reproductive ystem ( anadian ancer ociety, n .da). The gland unound s the base of the bladder a w ell as a portion of the urethra and its in front of the rectum ( anadian Cancer Society, n.da; Prostate Cancer Foundation, n.d.) . Prostate ize varie in men, but on average the pro tate is the ize of a walnut (Pro tate Cancer Found ation, n .d.). Sunounding the pro tate are the seminal vesicles, which are small glands involved in the ecretion of semen, and nerve that control erectile function run alongside and attach to the prostate gland (Prostate Cancer Foundation, n.d.). Although not essential for life, the prostate gland pl ays an e entia! role in reproduction through the production of protein and mineral rich fluid that nourishes and maintains sperm (Canadian Cancer Society, n.da ). Further, due to the prostate sunounding the urethra, muscle cells in the prostate gland also play a role in controlling the fl ow of mi ne und r invo luntary nervous system control (Canadian ancer Society, n .da.) . The gland it elf i divided into anatomic regions, repmied as the peripheral, transitional and central zones (Pro tate ancer Foundation, n.d.). The maj ority of prostate cancer tumors develop in the peripheral zone, which is the largest area of the prostate (Canadian ancer Society, n.da) . This area is close t to the rectum and can ea il y be felt during a di gital rec tal examinati on ( ana dian ancer ociet , n.da ). he transitional zone i the middle of th pro tate gland and can enl arge with age, while the 15 central zone i fa11he t from the rectum and thu cannot bee amin d via digital rectal examination ( anadian Cancer ociety, n.da). Androgen uch a te to terone and dihydrote to terone (DHT) pl ay a cru cial role in the normal development and biology of the pro tate gland ( irling, Whitaker, Mills, & Neal, 2007) . However, the e potent mal hormone areal o requ ired fo r the development of pro tate cancer which is often referred to a a hormone depend ent cancer ( irling et al. , 2007) . These androgens exe11 their deva tating effect by bind ing to andro gen receptor (AR) in the cytopla m of th e cell that all ow the AR co mpl exe to enter th e ce ll ' nu cleus via nu cl ar translocation ( irling et al. , 2007) . Once in the nucleus, the AR complexes bind to specific DNA equ ences known a androgen response elements that promote growth of androgen respon ive genes (G irlin g et al. , 2007) . These gene are re ponsible for m any different cellular event , incl uding increa e growth, survival and the expression of prostate specific antigen (PSA) (G irling et al. , 2007). It i becau e of this process that treatm ent fo r prostate cancer is often aim ed at targeting the androgen receptors by redu cing androgens levels or by inhibiting androgen receptor activation (Gi rl ing et al. , 2007) which will be discussed further below . Prostate-specific antigen (PSA) is a protein produced by the cell in the prostate gland (NCI, 20 12) . It is cmrunonly found in semen with small amounts fo und in th e blood of healthy men ( anadian Cancer Society, n.db ). Mea uring PSA levels in the blood wa ori ginall y approved to monitor fo r pro state cancer disease progression in those dia gnosed with pro tate cancer, however with time it was recommended for use in conjunction with a di gital rectal ex amination to screen for prostate cancer (NC I, 20 12) . Thi te t continue to be u ed as a ' tum or marker' to mon itor pro tate cancer re ponse to treatment and to monitor for progre ion or recurrenc f di ease ( anadian ancer ciety, n.db ). uch, change to P le el in the 16 blood, uch a an increa e in P A during activ treatment or following treatment can indi cate poor re pon e or recurrence ( anadian ancer ociety, n.db) . Whil a decrea e in P A level often indicate re pon e to treatment ( anadian ancer ociety, n.db ). Until recently, creening for prostate cancer via a P A test was recommended for all men over the age of 50, how vera more ha been learned about th t t, recommendations are changing (N I, 2012). Test re ults are not definitive. levated te t result (>4 nghnL) do not indicate prostate cancer, as other benign conditi n can cause PSA elevations such as inflammation of the prostate (pro tatiti ) or enlargement of the prostate (benign prostatic hyperplasia) (NCI, 2012). Moreover, activitie uch as recent sexual intercourse, digital rectal examination or prostate biopsy can temporarily increase P A readings (Canadian Cancer Society, n.db ). PSA testing has also been associated with false positives, meaning the results suggest cancer though no cancer is present as well as false negatives, meaning the test fails to identify cancer (Canadian Cancer Society, n.db) . It is fm1her identified that PSA testing ha s led to the over diagnosis of prostate cancer, as testing may find cancer that poses no se1ious risk to a man's health , leading to unnecessary testing and treatment (Canadian Cancer Society, n.db) . Consequently, the majority of medical organizations and guidelines suggest patients are informed of the potential benefits and hanns of screening in combination with assessing per onal risk factors for developing prostate cancer (Canadian Cancer Society, n.db; NCI, 20 12). Prostate Cancer Treatments Androgen deprivation therapy (ADT) is the most widely used treatment modality for prostate cancer, most frequently used in tho e with metastatic or with high risk di ease ( anadian ancer Society, 2014a; Mohile et al., 2009) . It is estimated that at least 50% of tho e diagnosed with prostate cancer will receive thi method of treatment at some point in their 17 di ea e (Tadr & arz tt , 2011). It can be giv n a a ingle tr atment m dality r m combinati n with radiati nth rapy, either pri r t radiati n (n therapy ( anadian ancer ci ty, 20 14a) . in lude urge1-y uch a a radical pr th r m thod ancer f tr atment £1 r pro tat cane r tatect my r tran ur tlu·al re ecti n f th pro tate, active urveillanc (phy ical a e ment and P A te ting very chemotherapy ( anadian -adjuvant) or after radiati n to 6 month ), radiation, and ciety, 20 14a). Androgen D eprivation T herap y The clinical eU ct of uppr ing te t ter n I vel (androgen deprivati n) in tho with advanced pro tate can er wa fir t id entified by Hu ggin and Hod ge in 1941 (Perlmutter & Lepor, 2007). Androgen deprivation wa found to be related t either urgical ca tration or throu gh uppre ing the production of luteinizing hormone relea ing honnone (LHRH) by the hypothalamu u ing diethyl tilbe trol (D ) (Perlmutter & Lepor, 2007). ince that time hormonal suppre ion has been a widely accepted fonn of managing advanced pro tate cancer (Perlmutter & Lepor, 2007). DES wa eventually id entified to be associated with signifi cant cardiova cular ri sks (Perlmutter & Lepor, 2007), o in 1971 new form of hormone uppre sion were developed throu gh th e manipulation of th ixth amino acid of go nadotropin relea ing hormone (LHRH), resulting in a potent LHRH agoni t called Leuprolide (Perlmutter & Lepor, 2007) . Leuprolide was studi ed and accepted to be equ ally equi va lent in effi cacy to D with l s risk of cardiovascular toxicity (Perlmutter & Lepor, 2007) . Over the nex t everal decade everal other fonn ofLHRH agonist were developed and are currentl y in use tod ay uch a go erelin and triptorelin (Perlmutter & Lepor, 2007) . urrentl y, there are four phan11acological ' Ia s of mcdicati ns used for androgen depriva tion : lutei ni zing honnone rclea ing honn ne agonists ( HRH), nRH antagonist , anti -androgen and YP 17 inhibitor . LHRH agonist ' are cuiTentl 18 the pr [I rred mean f andr gen deprivati n m pra tic (HatTi Montgomery, 2009) . The includ e Leuprolid , a eith r intramu cular r ub utan 2012a · B , 201 2b· B Mo ta gh eJ N 1 n, & o er lin and Bu relin, which are admini t r d u inj ection , mo t commonly every , 20 12c; Harri tal. 2009) . Plea e refer t month (B pp ndix A, for more information on th mechani m f ac ti n, indicati n and m eth d of admini tration. Durati n of ADT remain highl y debated in the literature with regard to intermittent ver u continuou treatm ent (Am ri ca n ancer ciety, 2014 ). Regardl e s of durati n of do ing, patient will v ntuall y becom e re i tant t h rm ne ablati n and th e ca ncer w ill progre s de pite treatment, thi can occur over a peri od of month r year (Am eri can ancer ociety, 2014). Intermittent treatment can be given Dr fi xed peri od of tim e, for exampl e 6 mo nth on and 6 month off or given based n P A level respon e to trea tm ent (Am erican ancer ociety, 2014). Intermittent do ing allow fo r a break in treatment and thu a brea k from treatm ent related sid e effect (American Cancer Society, 2014 ). Consensu regarding disease free urvival between continuous and intermittent honnone therapy rem ain unclear, w ith orn e studi es suggesting continuous hormone ablation ha a small survival benefit (Ameri ca n Cancer ociety, 20 14). Generall y, ADT is used prin1aril y for those with m eta tatic di sea e; however it ha been shown to be effective as nco-adj uvant therapy prior to radio therapy fo r tho e wi th high ri k localized di ea e (Perlmutter & Lepor, 2007). Additi onall y, use has be n demon trated in tho e with localized prostate ca ncer, locall y advanced di recurrence, such a an increa in P ase, and those wi th a bi och mica! aft er a pro tatectomy (Perlmutt r & L por, 2007) . T he clinical benefit of ADT are not onl y related to lowing th progre ion of disease, but u e is also a ciatcd with imp roving ymptom for tho e wi th ymptomati metastatic 19 di ease. For example improvement in pain r lated to bony meta ta e p t void re idual urin e, urinary ymptoms uch as urgency and frequency and quality of life have been demon trat d (Perlmutter & L por 2007). On e initia l limitati on to initi ati on w ith ADT i th e ' fl are ph enomenon' whi hi re lated t th initia l urge oft to terone in th e body due to the timulation ofLHRH receptor (Perlmutter & Lepor, 2007). Thi i mo t frequ entl y prevent d with the administration of anti -androgen , which inhibit the effects of testosterone stimulation of the androgen receptors (Perlmutter & L por, 2007) . Side Effects of A ndrogen D eprivation T herap y Commonly reported earl y adver e effects include hot fl ashes, loss of libido and erectil e dysfunction, all of which coincide with achievem ent of castration levels of testosterone, which occurs in onl y a few weeks (Perlmutter & Lepor, 2007). Prevalence rates of these earl y sid e effects vary depending on type of androgen suppression; however rates related to LHRH agonists for hot flashes are approximately 40-77%, lo s of libido 100%, and erectile dysfunction 90% (BCCA, 201 2a; BCCA, 201 2b). These adverse effects will continue as long as treatment is continued (BCCA, 20 12a) . A variety of other side effects that have been documented in the literature are outlined in table 1. 20 Ta ble 1 Androg n D 'Privation Sid E./f eet ataract Impaired b ne mineral d n ity Acute kidney injury (Al- ham i et al. , 20 12; B eb -Dimm r et al. , 2011 ; Braga-Ba aria et al. , 2006; B y low et al. , 200 ; heni er, ubin, & Hi gano, 200 ; urti , dam, hen, Pruthi , & ornet, 2008; GrunfeJd , Halliday, Martin, & Drud ge- oate , 201 2; Hanin gton , Jone , & Badger, 2009; Hervou et et al. , 20 13; K atin g, 'Mall ey, & mith, 2006 ; Lapi et al. , 201 3; van Lond en, Levy, Perera, el on, & Green pan, 2008) . A comprehensive overvi ew of sid e effect i provid ed below, de crib ed in relati on to physical , cognitive and p ycholog ical sid e effects. To begin, phys ical id e effect will be describ ed in detail in th e foll owing ord er: impaired physical fun ction, m etabo li c syndrome and di abetes, cardiova cular di ease, andropau e, anemia, cataracts, impaired bone mineral den ity, and acute kidn ey injury. This will be follow ed by cognitive id e effects. Lastl y, psychologica l ide effects, such as depress ion and distress, as well a body im age and loss of masculinity will then be described . Ph ys ica l S id e Effects The foll owing phys ical id e effect will be pre ented below: impaired ph ys ical fu nction, m etabolic yndrome and di abetes, ca rdi ova cul ar di ea e, and ropau e, an mi a, cataracts, impaired bone mineral den ity, and acute kidney injury. Impaired ph ys ical fun ction . Functi onal decl ine w ith age ca n o cur natural ly du ~ to normal enescent change , however pecific illne e and th eir trca tmenL, , uch as DT, can furth er incr asc de line, w hich put pati ents at furth er ri k fo r morbidi ti c. and mortal it . 21 According to yup k yup k Perk and zorak (200 ) t to ter n play an important rol e in mu cle trength a well a th function of the nerv u al. a cited in oyupek et al. 200 ). dem n trat d declin uch y t m (B nifa zi DT r lated depl eti n in te t w ndurance, upp r xtremity trength and d report of phy ica l functi n, r 1 and vitality ( libhai t al. , 20 10; thi knowled ge, di cu inanne chi , V lpe et ter ne ha terity, a well a elf- yupek et al., 2006) . D pite i n of ph y ica l and functiona l decline have not been well de crib ed in the pro tate cancer literature (Byl w et al., 200 ). Metabolic sy ndrome and diab ete . oldenberg and Punthakee (20 13) defin e m etaboli c yndrome a at lea t three of the fol lowing criteri a: waist circumference greater than 102 em in m en or 88 em in women, eleva ted tri glycerid e (greater than r equal to I .7 mmol/L) , redu ced HDL (le than 1.0 mmol/ L in men or 1.3 nuno l/L in women), blood pres ure grea ter than or equal to 130/ 85 and a fa ting gluco e greater than or equal to 5.6 mmo l/L. In Braga-Ba ari a et al.'s (2006) cross sectional tudy, more than 50% of m en und ergo ing long tem1 ADT had evidence of metabolic syndrome. This association is likely related to th e profound hypogo nadi m associated with ADT which has been correlated with an unfavorable m eta bolic profile such a increased insulin resistance, increased bod y rna ind ex (BMI), and redu ced lean body m as (Basaria, Muller, Carducci, Egan, & Dob , 2005; Braga- Basaria et al. , 2006). Male hypogonadism ha therefore em erged as an independent ri k factor for metabolic yndrome, which in itself is a sociated with the development of diabetes and cardiova cular di ea e (BragaBasaria et al., 2006; Ford, Giles, & Di etz, 2002 as cited in Braga-Ba aria et al., 2006) . Tsai et al. (20 15) confirms the a ociation between ADT and diabete by highlighting three large cohort tudies repo1iing an increa ed ri k of diabete in thos with prostate ancer recei ing c mpared t non A T u er . Moreover, ADT ha been as o iated with in rea ed total DT when 22 chol terol by up to 10%, triglyc rid 11 %, all f which ha b by 26% and high d n ity lip pr t in by approximately - n dem n trat d within m onth f D initiati n ( aylor, Keating, & mith, 2009) . Thi a ociation ugge t ri k trati fica ti n, routine a e m ent f m tab lie pr fil e and ardi va cuJar ri k h uld be inc rp rated int pnm ary care. Cardiova cular di ea e. dem n trated ab ve, effect , uch a increa ed fa t rn a , deer a ed in ulin DT ha everal adver e phy io logic n itivity, and eleva ted LDL, choJ e ter and tri glycerid e , all of which ar ind epend ent ri k fac t r [! r cardi ova cul ar di ease and mortality (Ef: tathi u t al. , 2009) . trul y i an a ociati n between results. Keatin g et al. (2006) and vari ety f tudi e have been done t a certain whether th ere DT and cardi ova cul ar m rbidit y and mortality w ith c nfli cting a i, D 'Ami co, adet ky, hen and arro ll (2007) tudi e both demonstrated an increa ed ri k of cardi ova cuJ ar disea e a ociated with A DT, w hil e a 2009 study by Nand a et al. demon trated an increa e in all -cau e mortality in men receiv ing A DT among tho e with pre-existing cardi ovascul ar di sease. Efstathi ou et al. (2009) did not find the same association as their tud y findin g were not tati ti cally significan t. Andropause symptoms. Asthenia, gynecomasti a, night sweats, ho t fl a he , loss of libido and sexual dysfunction are collectively known a andropau e symptom (G run fe ld et al. , 20 12). These m ale climacteric symptoms are associated with hypogonadi m and are reported a one of the most physically and psychologically bothersom e ADT related effects ( ru nfe ld et a!. , 20 12; Nishiyama, Kanazawa, W atanabe, T erunuma, & Takahashi , 2004). !though some of the e ymptom may be reported with th e normal ag ing proce , onset of andro pau qui ck r and with greater everity in those receiving ymptom occur DT due to th e dra tic and rapid drop in te tosteron fr m th e androgen depl eti on of A DT ( run feld et al. , 20 12). The mo t common! reported ymptom of and ropau ea r hot fl a he , wi th up to 0° o of men treated with ADT 23 experiencing this adver e effect ( runfeld et al. , 2012). It ha been rep011ed that hot fla he related to ADT ar more frequent , more ever and la t 1 ng r than tho menopau e (Grunfeld et al. 201 2). related to female on equ entl y hot fla shes andre ultant ru ght weat can have a ignificant impact on daily functioning a both ymptom can hav a negative effect on leep which re ult in deleteriou effect with cogniti ve functioning, dail y accompli hment , enjoyment of relationship and activiti e , and overall feeling of w ell-being (Chevalier et al. , 1999; Roth & Ancoli-Israel, 1999; Leger et al. , 200 8 as cited in H ani ch et al. , 2011 ). Gynecoma tia a ociat d w ith hypogonadi m ccur v ry earl y n in ADT, usually within a month or two . Alth ugh not phy i logically ignificant, thi condition can cause significant distress and embarrassm ent impacting psychological well -being. H01monal changes related to ADT can ignifi cantl y imp act exual fun ction. Declin es in sexual function were reported a soon as two month after the initiation of ADT and continu ed for the duration of treatment. For those receiving sh011 term or intennittent ADT the negati ve effects on sexual function h ave been reported to last tw o or m ore years after treatment completion (Gay et al. , 201 3). Impotence, reduced libido and anorga mia are frequentl y reported in the ADT literature and are often associated with altered perceptions of m asculinity, conflict within intimate relationships, a sense of loss of intimacy and ultimately can significantly impact the quality of life of both the patient and their partn ers (Gay et al. , 201 3; Grunfeld et al. , 20 12) . Anemia. Anemia frequently occurs in those with cancer, occuning in m ore than 40% of cases (Dicatol, Plawny, & Diederi ch, 201 0). An association between te tos terone and hemoglobin levels have been in the literature since it was first identi fied in 1948 (Hami lton, 1948 as cited in ut1is et al. , 2008). These findin gs hav been fm1her confi1m d by sev raJ tudi with the knowledge that b th urgica1 and phann aco logical ( DT) a tration can impact 24 hemoglobin, often into the anemic range. Thi drop in hemoglobin i likely r lated to the declin in androgen and thu lo man·ow ( urti le of th rytlu· poi etic timulating ffect of androgen in the bone tal. , 2008) . Anemia i defined a a hemo gl bin le than 14 g/dl in m en and than 12 g/dl in women (Dicatol et al. , 201 0) . The r pmi d anemia i n m1ocytic in nature with decline in hemoglobin mo t ft n (Cutiis et al. , 2008) . n within three to nine m onth f initiating treatment linical con equence of an mia in m en receivin g ADT for prostate cancer include impaired qu ality of life a it can contribute to fa tigue and dy pnea on exerti n, but ha al o been id ntified a an adver e progno tic factor ( miis et al. , 200 8; Dicatol et al. , 201 0). Cataracts. Cataract are a chronic, progre ive, age related eye di ord er that commonly affects those over the age of 50 years old (American Academy of Ophthalmology, 20 ll ). Without treatment vi ual and phy ical functioning will progre ively decline (Ameri can Academy of Ophthalmology, 2011 ). Very few tudie are available that discus the as ociation betw een ADT and cataracts. Beebe-Dimm er et al. 's (2 0 J J) stud y used data from th e Surveillance, Epidemiology and End Results Medicare Database (S EER) that demonstrated an elevation of cataract incidence among those receiving ADT. This association is su pected to be related to the onset of other identified adverse effects of ADT such as metabolic syndrome (Beebe-Dinuner et al. , 2011 ). Impaired bone mineral density. The potential effect of ADT on bone mineral den ity has been widely explored in the literature. Those receiving ADT have demonstrated a 5- l 0 fo ld increase loss of bone mineral density at multiple skeletal sites that is related to the hypo gonadal state induced by ADT. The significant decline in circul ating estrogen and t stosterone level cause increased rates f bone resorption as well a impairment o f new bone formation ( 1ham i et al. , 201 2). hange to bone mineral density can be n wi thi n month of ADT 25 initiation, with maximallo n ted within the fir t y ar of tr atment (Al- ham i et al. , 20 12). Annu al bone loss in the older male population i e timat d to be 1% while bon e lo receiving ADT i more rapid with many tudi e e timating the lo (Mohile et al. , 2009). Thi lo in those to b 1-4.6% annually of bone mineral den ity along ide ADT a ociated d cline m lean mu cle mas increa e the ti k of o te poro is, fall and fracture (Nadl r et al. , 201 3). Some studies have reported the ri sk of fracture to be as high a 20% by 5 year of ADT treatment which is twic th ri k identifi ed in m en with pro tate can cer not receiving ADT or healthy control (Nadler et al. , 20 13). Impli cation of osteoporotic fracture includ e pain, depre ion, fatigu e, functional imp ainnent, increa e m01iality rate by up to 20% and a significant cost to the health care system (Nadl er et al. , 201 3). Acute kidn ey injury. Recent development in ADT re earch have id entified a po sibl e connection betw een the hypo gonadal state induced by ADT and ac ute kidney injury (Lapi et al. , 201 3). Lapi et al. (2013 ) highli ght that other ADT related adverse effects such as dyslipidemia and hyperglycemia associated with metabolic syndrome may imp act renal glomerul ar functi on via the expansion and thickening of the interstitial tubular membrane (Lapi et al. , 20 13 ). It is al o suggested the vasodilator effects of testosterone are lost when A DT depl etes testosterone to castrati on levels impactin g renal tubular fun cti on (Lapi et al. , 20 13). Lapi et a l. 's (2 0 13) case control study is currentl y the onl y observational tudy investiga ting this association and di d demonstrate an increased ri k of acute kidney injury with ADT. a result of this relatively new finding, data is relatively limited in the literature regarding ADT and it associated effect on the kidney, which accounts for the limited data provided here. Nonetheless, thi s si de effect must be considered [! r this pati ent population . As the above has highli ghted, there ar a variety of 26 phy ical id efD ct t ADT that m u t b c n id r d when pr viding ar to thi pati n t populati n . M ving D rw ard , the cogniti e effect Twill b addre ed . f ognitive ide Effect Th D 11 wing w ill pre ent th have 1 ng been a f cia ted with a vari ety [ can itiv r lati n hip b tw en t t function , patial m m ry and abiliti a ociated with .A gnitive change r trea tm ent , h wever edu cation, creening and upp rt don t app ear to b inco rp rat dint cancer care. note a p T n cogniti n . henier, Aubin and Higano (200 8) t r n and c gniti ve functi n u ha x cutiv uch, tudi e have id entifi ed th e hypo gonadi m DT wa related to impairment in verb al m emory, attention and pati al abiliti e ( herri er et al. , 200 ). Furth r, a demon ira ted by herri er et al. ' (2008 ) tud y, c gnitiv e chan ges were noted a earl y and m o t pronoun ced w ithin three m onth of A DT and orn e but not all cognitive change related to A DT might return to ba eline fo llowing ce sati on of ADT. The literature also id entifi e that often cogniti ve changes in tho e receiving ADT are erroneously believed to be associated to age rath er than the trea tm ent by both pati ent and provider w hi ch m ay be related to a lack of informati on regarding the potential impact of treatm ent on cogniti on . Moreover, id entifying cogniti ve imp airments in thi pati ent popul ation is e entia! as impairm ent can nega tively impact cancer care, outcom , trea tment tolerability and pati ent decision-m aking (M obile et al. , 201 0). Fina ll y, the psychological id e effects and their impact on health and well-being will be di cu ed below. Psychological Sid e Effects T h p ychol gica l equ elae o f A DT, uch a depre ion and d i tr b dy image and los of m asculinity w ill be pre en ted. fo llowed by altered 27 D epre ion and di tre . The overa ll pre alen e timated t be b twe n 15 -25%, while th hi gher ri k ba d n cun- nt r ea r h ( and di tre rec 1Vll1g I, 2014 ). How of d pre i n in th DT ar prop er d e with cancer i ed t b at an ven pit it preval nee, d pre JOn are und r r cogniz d and und ertr ated whi h can impact m dical adherence, increa ed morbidity and p 1998 · Ri chard ibl y m rtality (Pirl, iegel, de, mith, 2002; H en111ann et al., K at , 1996 a cited in Pirl et al. , 2002). Du t th e n et al., 1990; pi egel potential impact, th id ntifi ca tion and tr atm cnt f p ychologica l i u related to cancer and it treatment have beco me increa ingly id ntifi ed a an important a pect t c mprehen ive cancer care (Vodermaier, Linden, & iu, 2009) . More v r in an attempt to increase reporting f psycholo gical issue and le en the tigma a ociated with p ycholo gica l c nditi n , terminology has shifted from langua ge uch as depre sion, p ychi at1ic, em oti onal or p ychosocial i sue to the term di tre . The link between testosterone depletion and depre ive yrnptoms wa fir t identified in 1995 , however ince there ha been co nfli cting re ults of th e impact of ADT in relation to mood disorders (Hervouet, avard, Iver , & avard, 20 13 ). Animal model have demonstrated altered neurotransmitter levels, such as serotonin with low y temic testo terone, which can negatively affect mood ( aini et al. , 20 13 ). Further, studi es involving eld erly, noncancer patients have dem onstrated an as ociation between low te to terone and depre 1ve ymptoms that resolved with testosterone honnone treatment (Saini et al., 20 13 ). Altered bod y ima ge and lo s of ma sculinity. Body image can be defined a "the dynamic perception of one's own bodi ly appearance, function, and en ati n a vvell a ~ eling a ociated with thi perception. It occur larg ly at a ubcon ciou I vel and i normall regulated by the condition Badger, 2009). f the body'' (Dropkin, 1999, p . 10 a cited in Harrington, Jones , van (200 1) a c ited in li [[e (2006) note men traditional! pia 'e a hi gh valu 28 on pecific qualitie and characteri tics uch a phy ical trength and the id al male b dy, which is intricately connected with embodi ed rna culinity. Therefor adv r e changes to bod y ae thetic , uch as brea t t ndem e and enlarg m nt and th 1 can create ignificant p ychological di tre ( aini et al. , 201 3 ). f p nile length and volume ther lit rature ugge t that ADT re lated chan ge a oc iated w ith dec line in te to terone, uch a hot fla she and mood change are ema cul atin g and wor en · ~ minin e behav iour ' like If-image and perception ( zieful a, Grunfeld, & Hunter, 20 13). Wor ening self- image and perceived los of masculinity can be further perpetuated by other effects of ADT treatment, uch a declining libido, energy, body shape, ability to work (Harrington et al. , 2009). avo n and Morag (2 003) as cited in Harrin gton et al. (2009) identify the e changes to body image can crea te emotional distance in intimate relationships impacting the quality of life of both partners. Provided above is a comprehen ive de cription of the phy ical, cognitive and psychological sid e effects of ADT highli ghted in the literature. The next chapter, research and m ethods, will provid e a de cription of the literatu re search that was completed in order to answer the research question. The process, such a the identifi cation of search terms, inclusion and exclusion criteria, and creening and earch outcome will be described. 29 hapter Tw Re earch and Method Th g al of th literature ea r h wa t an wer the qu pnmary car pr tion : etting, what creening i required to id ntify ide effect tate cane r. r P practi cing in a f Tin m en with arch t rm [! r th e literatu re review w re elected a th y repre ent the va ri u term applicable t the qu e tion being ar h d . neopla m, androg n ablativ th erapy, andro arch term included prostate cancer, pro Latic n deprivation th erapy, primary car w; essm nt , screening, and fo llow up . ln ord er t narr w th e earch an d yie ld finding r levant to ADT and creening of id e ffect , a combinati n of teJm were elected , using ubj ec t hea din g and th e Boolean phra e 'a nd ' . For exa mpl e, androgen d 'Privation th erapy and patient assessment, androgen deprivation and creening, androgen deprivation and screening /or side effects. androgen deprivation and fo llow up. However, very few finding accumul ated from thi earch critetia, therefore lightl y broader search term such as androgen deprivation th erapy and side effects, depression and androgen deprivation th erapy, anemia and androgen deprivation th erapy, metabolic y ndrome and androgen depriwttion therapy, and sexual dy.~fun ction and androgen deprivation th erapy. The inclu ion and exclusion cri teri a appli ed co n i ted of the following : 30 Tabl 2 lnclu ion and Exclu 10 11 lnclu ion rit ria riteria : No limitation to dat f publi h d paper Arti cle writt n in th ngli h language M en with pro tate cancer (all ethni citi e ) No limitation to ag r tag of di ea Included at lea ton e tudy group re iving andr gen depriva ti on therapy (ADT) Both quantitative and qualitati v tudie were included Publi shed paper were n t limited t anada alon du e t limited earch re ult Primary care etting Exclu ion riteria: Publi hed paper without recommend ati on fo r creening/a e ment of sid e effects Acute care urvivorship care lnclu ion criteria included m en with pro tate cancer (a ll ethni cities), however wa not limited to age a ninety- even percent of all prostate cancer di agnoses occur in those over the age of 50, how ever some individuals are diagnosed at a youn ger age (Prostate Cancer Foundation, 20 14 ). All sta ge of disease were includ ed. Further, the search was not limited to recent stu die as the effects of androgen suppression have been reported in the literature since Huggin and Hodges' initial stud y of andro ge n depri va ti on in th e 1940 ' (Perlmutter & Lepor, 2007) . Treatment with ADT was inc luded in all tudi es, however election of tudi es wa not limited to prostate cancer patients receiving ADT alone in order to allow for compari on of adver e event between other treatment modalities and healthy control s. Both qualitative and quantitative tudy d signs were included in order to identify a broad account of DT ide effects and them identify how these ide ef~ ct were screened in a re earch capacity, and wh ther the , method of screening such a va lidated creening tool may prove relevant or be recommended for clinica l practice a ses ment of side effects. ualitative studie were specifically considered as 31 open nd d que ti n all w d £ r d further adv r ef£ ct cripti r f1 cti n n ide ffect which may identify r th me that h uld be c n ider d D r ere ning but may n t be id ntified thr ugh quantitative de ign . A countrie . anadian guideline and literature were limit d, inclu ion criteria includ d ther verall, inclu ion criteria remained broad a data pertaining t up wa limited . Br ad crit ria a! event related to creening and £ llow all wed for the ability t ga in in-depth in ight into adver e DT in order to hi ghli ght gap in creening in primary care. xclu ion included article that did n t provid cree nmg rec mrn endation for primary care, acute care, po t treatment care and £ 11 w up ( urvi vo r hip) . The literature earch began with a earch of the fo ll owing four electroni c databa e : Cochrane library, INAHL, Pubmed and Joanna Briggs ln titute Library. The majority of the searche utilized medical ubj ect headings in order to facilitate appropriate data retri eva l by accounting for various terminolo gy and ubject matter for th e topi c of interest (Na tional In titute of Health, 20 12). Ba ed on the above earch terms, a total of 1198 at1i cles were identifi ed . Us ing the University of Northern Briti sh Co lumbia 's library re ources for direction, a search of the grey literature was then done. This included a search of the following: clini cal practice guidelines and protocols for British Columbia, Canadian Nurse A ociation tandard and best practices, anadian Medical Association InfoBase, National Guideline anadian Agency for Drug and Technologic in Hea lth and ( A tandard and learinghou e, uideline Evidenc ). Guidelines were canned and included in the earch re ult if they included any a pect of screeni ng, recommendation or follow up. oogle cholar and the World Wide Web were also searched u ing the ame earch ten11s and phrases a above. The earch revealed an additiona l 140 potentially relevant material . inally, the reference list for all full text eli gible 32 paper were cam1ed and a total of three additi nal paper w ere identified. In the end a total of 1341 potentially relevant mat ria l were id ntified, retriev d and exp tied into ndnote. Screenin g and earch Outcom e The literatw· review id entifi d a t tal of 1341 potentially r levant pap er . After ere ning titl and ab tract fo r uitability, thi number wa nan wed down to 50 arti cle for further review . Full tex t article were then reviewed, 28 of which were excluded ba ed the on inclu ion and exclu ion criteria . After thi proce , 22 eligibl e papers w re available for review ( ee Appendix B fo r fl ow chart). The next chapter will di cu th e findin g of the 22 papers identified in the review . Thi will begin with twelve individual research studies, fo llowed by five clinical practice guid eline , fo ur clini cal review and one editorial. 33 hapt r Thr Findin g The arch trategy d re earch que ti n: r ribed ab ve identified 22 miicle to a i tin an wering the P pra tieing in a primary car identify ide effect in men with pr tat etting, what ere ning i r quir d t anc r rece1 mg T. The £i 11 wing chapter will pre ent 12 individual re earch tudie , u ing b th quantitative and qualitative de ign to provide in ight into pecific creening r co1run ndati n . The lit rature frequ ently de cribe ADT ide effect by a focu n phy ical, c gnitive and p ych logical alteration of function; therefore data from the individual tudie will b pr sented in a imilar fa hion. Following individual tudy finding , the finding from fiv e cunent clini cal practice guideline , four clini cal review and an editorial will be analyzed with regard to recommendation for creening for those receiving ADT for prostate cancer. Finding from clinical practice guideline , clinical review and editorial s are deliberately pre ented a a whole rather than throu gh individual phy ica l, cogniti ve, and psycholo gical side effects in order to demon trate the gap , limitations and str ngth of each. To begin, cunent recommendations for screening of phy ical, cognitive and psychological side effects from 12 individual research studie will be hi ghlighted. everal topi c are noticeabl y ab ent from the e studi es, such a follow up interval , cardiovascular disease, cataract and acute kidney injury, which account for the diver ion from previou ly organized paper subheadings . However, recommendati on for these topi c are de crib ed in other re earch materials, such as clinica l practice guideline , clinical reviews and editorials, whic h will be pre ented 11 llowing indi vidual studie Ph y ica l id e ffects Ph y ical fun ction . r the 12 r ea rch tudi c revt wed, onl y one tudy described 34 phy ical and functional impairment with creening reconunendation . By low et al.' (2008) study inve tigated the prevalence of fall , phy ical and functional impairment in tho e receiving ADT for ymptomatic meta tatic pr tate cancer. Fifty patient over th age of seventy w re rectuited from a convenience ample of men being treated at the Univer ity of hicago Genitourinary Oncology clinic . 11 patient underw ent a comprehen ive geriatric as es ment at baseline, which was then repeated after three month of ADT treatment (only 40 patients had the repeat as essment a 10 patient were lo t to D llow up) . The comprehensive geriatric as essment included an assessment of functional m ea ures, risk for functional decline, physical fun ction, history and risk of falls, mental status, nutritional as essm ent, social supp011, and fatigue using tools that have been validated in the elderly population. Functional m eas ures such a activitie of daily living (basic elf-care), instrumental activitie of daily living (activitie required to live independently such as banking, meal preparation and hopping), and th e Vulnerable Elder Survey (YES) were done to assess risk of functional decline. The YES is a 13 item, self-reported screening tool used to identify geriatric pati ent who are risk for functional decline. Physical function was assessed using the Short Physical Perfonnance Battery ( PPB) , which assessed the physical function of the lower extremities throu gh three tests of balance, gait speed and quadriceps strength. The other tools utilized in the geriatric assessment included the Short Portable Mental Status Questionnaire, Charlston Comorbidity Index, Medical Outcome Social Supp011 Scale, the Mini Nutritional Assessment, and the Medical Outcome tudy tudy hmi Form 36 item health survey. Deficits were noted in balance, walking and chair stand in 56% of patients, 24% had impairments on activities of daily living while 42% had impainuent in in trumental activitie of daily living. At bas line, 22% of patients had reported fall within the previous three month and 56% noted additional fall after trcatm nt had been initiated . a 35 re ult of the in rea d ri k for fall , th abnormal phy ical p r£ rman thi tudy i th u tudy auth r id ntifi ed a need for routinely c rcening D r and ri k for fall in thi p ati ent p pulation. maJOr tr n gth to of to 1 that ha ve been alid ated £ r u e with the elderly populati n. Howev r, du e to a mall ample ize and th e nature f th e cr relati n hip between ctional tud y, a t mporal DT, abnonnal phy ical p erformance and fall c uld not be reliably establi bed r gen raliza ble. Metaboli c yndrome and di abete . Two indi vidual re earch tudi es id ntifi ed m taboli c syndrome and diab ete a ide effect to A DT. A cro ecti onal tud y by Ba aria et al. (2005) evaluated the ffect of long term ADT u eon fa ting gluco e level , in ulin level and in ulin re istance in m en with prostate cancer. Three group were tudi ed : with prostate cancer who were receiving roup 1 co n isted of 18 m en DT for 12 month prior to the tudy, group 2 included 17 men with non-meta tatic prostate cancer w ho had not received A DT, and group 3 wa mad e up of 18 healthy controls. Param eters such a age, race, and BMI were docum ented along with objective measures of total and free testosteron e levels, Jeptin, fa ting glucose and insulin level Leptin is involved w ith long tenn regul at ion of en ergy balance, sup pres ion of food intake and weight loss (Klok, Jakobsdottir, & Drent, 2007) . H owever, intere tingly, o bes individual typica ll y demonstrate hi gh Jeptin levels, which ugges ts leptin re istance (Klok et al., 2007). Fasting glucose refer to a erum blood ampl e that refl ect the gluco e (sugar) concentration to which the body tissues are expo ed (Hess-Fischl, 20 15) . Insulin i a hom1 ne produced by the pancreas that all ows the body to u e glucose deri ved from food intake for energy or to tore gluco e for future u se (He -Fischl, 20 15) . leva tion in fa ting glu o e level demon trate th e bo ie , inability to produce enough in sulin r th e development o f in ulin re istan e, bo th which in rea e the ri k f developing diabete , (He -Fi c hi , 20 15) . or 36 ignificant nega ti in ulin and leptin level . correlati n wa n ted b tw e n tc t Thad high r fa ting glue dditionally, m n wh had r c ived e DT gr up (p= O.O1) and the c ntr I gr up (p< O.OI). In ulin le el when compared t the n n le el were al o mu h hi gher in the 7.24 u /mL in then n ter n and fa ting gluco e, T gr up ( 45 - 7 .25 u /m ) in c mpari on to 24.0 +- T gr up (p=0.05) and 19.0+ - 7 . 9 u /mL in th e co ntrol group (p= 0 .02) . Finally leptin leve l wer al hi gher in the ADT group (p 25), obe e (BMI >30) or over th e age of 45. For those receiving ADT for prostate cancer, stud y authors identify creening should occur prior to the initi ation of ADT and then repeated annu ally. Study strengths include use of a c ntrol group, a large sample size and a long peri od of fo ll ow up . Further, potenti al cofounding effects such as age, race/ethnici ty, year of d iagno i , comorbidities and health pl ans were adjusted fo r. However, there i no mention as to wheth er the stud y contro lled for all ri sk factor associated with di abetes. Three stud y limitati on wer noted w ith the fir t being p tential for selecti on bi a given the stud y de ign wa an ob ervationa l tudy. ec ndly, a hemoglobin A 1 of 7% was u ed to e tabli h th e di agno is of diabctc rather than th e 6.5% w hich may have mi ed ome parti c ipant with earl y di abet s. Fina ll y, a the parti cipant were elected from the l-IM y tem gcn rali za bility to non-HM system. ma be 38 limited as HMO likely promote and upports prevention and early detection of diab te . Andropau se syndrom e. f th 12 individual r earch tudies, only one pecifically looked at andropau e syndrome in relation to creening rec rmn ndation . Through qualitative interviews, Grunfeld et al. (20 12) expl red the prevalence and impact of andropau se ympton1 in men with meta tatic pro tate cancer und erg ing ADT. Twenty-one patients were rec1uited and underwent emi- structured in per on or t lephone interview . Interview que tion were developed based on previou re earch, and discussion with a uro logy nurse specialist, psychologists and urologi t. Interviews were conducted using open end ed qu estion , with loo e structure that focused on area of predefin ed intere ts uch a sid e effects of ADT and coping strategies, however allowed for discussion of issues as they emerged in the intervi ews. Four main side effects to ADT were identified, gyn ecomas ti a cogni tive decline, change to sexual function, hot fl ashes and night sweats. Approximately half of the patients reported gynecomastia and or breast tenderness, while 71% expetienced night sweats and hot fl ashes, all of which were a source of emban assment. N ight sweats also significantl y contributed to di sturbed sleep patten1s which resulted in daytime sleepiness . Additionally, reported changes to sexual fun ction such as interest and physical capability, varied depending on the patients age and ma rital status. For example, sexual dysfunction uch as impotence or reduced libido was more commonly accepted in those that were single or if their partner had a low libido. Others deemed sexual dysfunction to be a major concern, particularly related to concerns about di sappointing their wives, while others discussed the impact on masculinity. Di sclosure of ymptoms was variabl e, with most limiting disclosure to close famil y. Surprisingly this study fo und many of the participants had a de ire to corm11ence e ual acti ity, however very few had received treatment for erectil e dy fu nction (ED) or were of:D red 39 coun lling ither £ r them lv or th ir intimat pat1:n r . Thi lead one to c n id r whether pati nt are being ad quately cr en d for andropau ymptom , tud y auth r ual dy functi n . Ba includ e an appropriat Ii r th e P P to a k ab ut ide mpha ized th importan effect to a i t m n in actively and op nl y di c u ing b th r d on he itancy t di cl m e concem . tudy tr ng th ized ample gr up with an adequ at numb er of m aningful and de criptive qu tati n that mpha ized th ccurr nee and meaning of DT id e effect . Additionally, interview qu e ti n app ared t b evid ence ba ed and pi! ted which allowed £ r gathering of pecific in£ m1ati n an opp 11:unity to di cu th r i u u ght by the tud y author and p articipant were a! o pr vid ed allow ing for th e p otenti al development f n w them e . Limitation may includ e limited info tm ation regarding th e interviewer , su ch a age and ex which may alter participant 'w illin g nes to di clo e sen itive i ue . Anemia . nly one research stud y identifi ed an emia as an conjunction with creening recommendations. DT re lated ide effect in urti e t a l. ' (2008) r tro pecti ve chart review of metastatic pro tate cancer pati ents receiving ADT attempted to confinn the as ociation between anemia and A DT and identify w hether patients were clini call y symptomatic with their an mia . A total of 135 ca es were reviewed, all of which had received some fon11 of ADT. Case review included treatment type (single or combination ADT), hemoglobin and mean c rpu cular volum (M V) levels prior to initiating ADT followed by mea urements of the e three and nin month after starting treatment. Patient chm1: were reviewed to asses Ii r reference noting the pre enc of ymptom logy related to anemia ( uch as dy pnea and fatigue) . f the 135 chart re iew ed, 43 patients had laboratory data uffici nt to be included in the final analy i,. hem globin value , by - 1. 11 g/dL, wa noted in all patient r cciving dec line in DT (p 0 .001 ). N om1 al hemoglobin va lue for men are appro imately 1 .2 t 17 .5 g/d , mean valu e or hemo globin 40 prior to DT treatm nt initiati n wer 14.12 g/dL while valu e b tween thr e and ix m nth rev al d a h mogl bin valu in th anemic range (1 .0 1). M V 1 v 1 al o dem n trated a decline at ix month , with a volum of 9 .5 fL. Finally, 7% ( 16 out f 2) patient exp ri need ymptom of anemia. maj r limitati n t thi vari ty of ADT treatment th refo re the chang one method of ADT alone. Ba ed n the prevwu tudie it wa tudy wa that many of the pati nts received a t hem globin c uld n t b olely attributed to tud y finding al ng ide imilar tudy finding from ugg ted by tudy author to creen for anemia and its ymptom after tarting ADT, although pecifics ar not includ ed. Impaired bon e min eral den ity. Three f the twelve tudi e reviewed looked at bon e mineral den ity. Yu eta!. ' (20 12) tud y demon trate th e e han ges thr ugh inv tigating th e change in bone mineral density and fracture risk with intermittent treatment with ADT. Fifty-six patients with non-metastatic prostate cancer were recruited for the study. Pati ents were treated with nine months of ADT and then di continued until pro tate pecifi c antigen (P A) reached 1 ng/mL for those who underwent a radical prostatectomy and 4 ng/mL for tho e who underwent radiation and ADT. When the e PSA thresholds were met, ADT wa reinitiated for another 9 months of treatment. Dual energy x-ray absorptiometry (DEXA) scans, CT can , bone scintigraphy and lumbar spine x-ray were done prior to stmiing ADT and repeated with each ubsequent change in therapy (beginning and end of each treatment) . Of the 56 patient , 3 8 had n nnal ba eline bone mineral den ity. f the 38 patients with normal ba eline re ult , 13 .2° o developed o teopenia during ADT treatment. Further, re ults d monstrated an 80° o deer a e in b ne mineral density of the spine and 56.4% decline in bone mineral d n ity of the 1 ft hip during the fir t treatment period . Additionally, bone mineral density reco er of the pme wa een during the fir t off treatment period , with an average ' hange of 1.4%. Unfortunately, 41 veral patient dropped out of the tudy due to DT treatm nt failure which may limit th tati tical p wer f there ult . R ult may al b influ need by individual bi 1 gic and nvir nm ntal factor . Alth ugh n t pecifi d ifD X can w r ped rmed with different machine at different facilitie , the c uld p tentially influ nee the re ult malJ incon i t nci a w 11. Ba ed on variability of b ne mineral den ity change throu gh ut trea tm ent period and the known ft ct of DT, continu d and r gular monit ring with ca n wa id ntified by the author of the tudy. Ba d n the well documented effect of DT on bone density in the literature, Al- ham i et al. (20 12) examined care gap with regarding to creening, prevention and trea tment f osteoporo i in men with prostate cancer receiving DT. Thi retro pecti ve tud y consisted of men with non-meta tatic pro tate cancer who received ADT betwe n 2008 and 2009. Patient were selected ba ed on treatment at the J uravin.ksi ancer Centre in Hamilton Ontario and identified by their hormonal therapy treatm ent billing number. A total of 149 men' chart were reviewed and data such a age, date of prostate cancer di agnosi , sta ge of di ea e, and la t P value were documented. Risk factors for osteoporosis such as previou fracture , hyperthyroidism, use of corticosteroids, diabete , smoking or alcohol use wa a! o obtained. Finally, presence of osteoporo is screening characterized by a baseline or ubs quent dual x-ray ab orptiometry (D XA) was docu mented . Study re ult detetmined a large population of participants had risk factors pre ent foro teoporosi , with five parti cipant having previou fractures, 13 .3% alcohol abu e, 49.3% had a hi tory of moking, 16.7% were cuiTent ' moker , 3.3% had a hi tory of cortico teroid use and 2% had a hi tory of hyperthyroidism . Ba elin D XA can wer d ne in 58 .8% of men receiving some point a ~ llow up . T and 20 . 0 o of which had repeat 'can. at nly 28% of participant had both a ba elinc and follow up X 42 can. ftho lin 12 w r ~ und to hav a bon mineral den ity in th cr ened at ba o t op rotic range (T c re of -2.5 r gr at r) and 1 pati nt had aT c rein the range ( -1 to 2.5). It wa al o found that th e with increa more likely to be creened while age, tage r P f ADT inj ection were at initi al vi it did n t impact creenin g. It i noted by the tud y auth r that ere nin g ~ r World Health d number teop enic rgani za ti n fractur ri k a e m nt t teo p ro i with tool , such a the 1 ( RAX) a well a a ba eline D XA can prior to ADT initiati n h uld be con id ered. tud y findin g w re limited to data being retri eved from a ingle cancer center th at may impact generaliza bility. Further, data was obtained fro m a retro pective chart revi w; therefore data ma y not accurately refl ect the clinical care patient received. trength includ e an adequate di cu ion regardin g impli ca ti ons for practi ce a well as pecific recommendati ons that may c ntribute to improved care for thi pati ent population. A mentioned above, althou gh th e data wa obtained from one care center, data found in thi cunent study was supported by other tudies done in other in titutions th at as i tin validating the study findin gs . Similarly, M orga ns, mith , O'M all ey, and Kea tin g (20 13) asse ed bone den ity te ting among men with prostate cancer receiving ADT for one yea r or greater. Men were identified from the Surveillance, pidemiology, and End Re ults ( EER) which i a National ancer Institute program that collects data from cancer regi tri es in the United tate . Patient selected were diagnosed between 200 1 and 2007 and over the age of 65 . Jtimately 28 ,960 men were elected with local/regional di ease. Men with meta tatic di ea e were excluded from th e tud y a bone mineral density te ting in this population i not reliable . Bon den ity tc. ting data wa documented six month before DT initiation for a total of 1 months . Rc ' ult demonstrated only l 0.2% of tho e receiving DT [! r more than one year had bone mineral density tes tin g 43 done 6 m nth prior to ADT initiation t over tim a 14.5% f m n wh initiated ver u 6% ftho e wh tarted f creenm g 111 rea ed ne year aft r tr atm nt. Rat T in 2007 -2 008 had b ne mineral den ity te ting DT in 200 1-2 002. urther, ld er m en (over ag bone mineral den ity t ting d ne than th 5) had Je e in th e 66 t 69 ag rang a did black m n ver u white m en and tho e with I wer edu cati nal atta inm nt. tud y auth r continu e t ndor e b ne den ity creening and enc urag additional ef£1 r1 t pr m te creening. trength f the tudy include a large ampl e ize, m derate 1 ngth of [! 11 w up , and broad patient chara cteri ti c which would ace unt for genera li za bility. Limitation how ever include timing of the tud y, a the stud y began prior to signifi ca nt evid enc in the lit rature rega rdin g ADT's effect on bone hea lth. Therefo re, limited knowledge of ri k like ly impacted the very low creening rate in the arly year of thi s stud y. econdl y, reco mm endation for testing by PCP versu patient refu al to complete testing wa not abl e to be d tennin d. Further, testing was done in those enroll ed in M edicare therefore par1icipation in testing ma y vary depending on m edical coverage. Unfortunately, th e literature failed to id enti fy a large number of studi e di scussing specific physical side effects alongside screening recommendation for many of the ide effect . This i true for physical function, metaboli c disea e, di abetes, andropau e and anemia, with only one study found for each . In this case, one mu t be cauti ous when interpreting there ult and consider tudy methods, design and number of participants which can limit or trengthen study findings . For examp le, Tsai et al. (20 15) and Morgan et al. (20 13) tudy' included very larg samp le with long follow -up, w hich helps toe tabli h creditability of tudy re ult . cction wi ll pre ent tudy finding related to the cognitive ide iTect ogni tive id e ffect f DT. he nc, t 44 Although ev ral tudi have been condu ct d t id ntify DT effe t on cognition, only one tu dy wa identifi din the literature arch that m et the inclusion and exclu ion criteria for thi review . Mohi le eta!. ' (20 10) tud y ught to id entify the prevalence of cognitive impainnent and change to c gnitive p er£ rm ance over tim in thirty- tw m en with pro tate cancer receiving ADT . A vari ety of tandardi zed neuropsychol gical a es ment t ol were u ed to as e s attention, language verb al m emory vi ual memory , visuospati al planning and motor proce ing. The e tool were p ecificall y elected ba ed on th ir establi bed reliability, validity and en sitivity. A sse m ent tool included were: The Trail M aking te t (attention), Di git pan (attention), Controll ed Oral W ord As ociati on Te t (language and emantic flu ency) , T he Rey Complex Figure Te t-Copy Trial (visuo patial planning) , Hopkins V erb al Learning T est-Revised (verbal m emory), Brief Vi ual Spatial Learning Test-Revi ed (vi ual memory), Grooved Pegboard and Finger T apping tests (motor peed and dexterity) , B ecks D epression lnventory-2 (depression), and The State Trait Anxi ety Inventory (anxi ety). Assess ments were don e by a trained psychometrician within two weeks of starting ADT, and repeated ix m onths later. Surptisingly, at the time of baseline m easurem ents 45% of participants scored grea ter th an 1.5 standard deviations below the m ean on tw o or more neuropsychological measures, with no changes in cognition noted after treatment initi ation. However, 3 8% of the to tal cohort demonstrated a decline in executive functioning at the six m onth assessm ent. Based on the e findings study authors suggest pati ents be screened for cognitive impaim1ent prior to consid erations of ADT and possibly throughout trea tment regimen , p articularly if pati ents are more vulnerable to developing life altering conditions such a dementia . tudy strength include con idering potentia l cofo un d r such a an i ty, d pr ion and edu cation. Limitati ns includ e a hart fo llow up time of 6 month which leave long tem1 effect 45 of ADT till unknown. Further limiting the tudy r a ment with only 65 % of m n c mpl t d th p may have impact d there ult . dditi nall y, th ult i p or completion of follow up t tr atment D llow up evaluati n , whi ch mall ampl e ize with ut the u e fa contro l group limited the tudi e ability t identify th e impact [ T n c gnitive chan ge . The e stud y finding ma y be u ed in c njun ti n with th er finding in th literatur which ugge t impact cognitive function . The p ych logical ide effect of D DT were id entifi ed in three individual re earch tudi e and will be presented below . P ych logical ide effect include depre ion and di tre foll w d by alt red b dy image and lo of ma culinity. Psychological Sid e Effect Two tudi e identifi ed depre s ion and di tre a DT related id e effect . Lee et al. , (20 14) longitudinal tud y aim ed to identify depressive symptomology in m en receiving ADT for non-metastatic prostate cancer. Participants were recruited between September 2008 and October 20 12 as part of a larger study examining qu ality of li fe in those rece iving A DT for pros tat cancer treatment. The sampl e con i ted of three gro up : 6 1 patient with pro tate cancer receiving ADT, 6 1 patients w ith pro tate cancer not receiving A DT (i nstead a radi cal prostatectomy) and 6 1 healthy control . ach prostate cancer patient receiving ADT wa matched to a participant in the non A DT group (p rosta tectomy) and con trol group . elf-rep rt questionnaires were completed by all participants with the fir t qu tionnaire done prior to th e initiation of ADT and again six month later. Depressive ymp tomology w ere a s d u ing a validated tool call d the -D) . With enter for pidemiological tudies Depr ion cal e (C thi mea ure, score range from 0 to 60, with scores above 16 indicating clinicall y ig nificant depres ive ympt ms. tudy re ult revealed an incrca c in dcpre ive symptomology (p 0.05) and in ·rcas 'd 46 rate of linically ignificant d pr ba 1v ympt mol gy (p 6 month ) ADT (NIC , 20 14 ). It i al o end or ed by the guideline that men rec iving ADT hould have acce I E (20 14) to erectil e dysfu nction enrice , PD 5 inhibitors and psycho exual coun elling, however m ethods and frequency of creening are n t provided. Additionally, it i recommended that as e ment for gynecoma tia i done within th e first month of treatment with ADT in order to offer appropriate trea tm ent such as prophylacti c radiotherapy or tamoxifen (NICE, 2014 ). Algoritluns for diagnosi of can cer and treatment are provided, however screening algorithms are not includ ed. Finally, th e fifth guid eline to be reviewed com es from the uropean A sociation of Uro logy ( AU) Prostate Cancer guideline . Thi guid eline was publi hed in 200 1 and mo t recently updated in 2015 . The AU (20 15) guid elin s address follow up, p ycho logical coping, as well as laboratory and diagno ti c investi gation for screening for diabetes, anemia, r nal function, and bone mineral density. lini cal follow up is empha ized a mandatory for all patient receiving ADT ~ r the trea tm ent of prostate cancer. Al though p cific recommendation~ for timin g and m th d of creening are made, it i , noted that follow up 'hould be tai lored ba ed 52 on individual ymptom , treatment modality and progno tic factor . enerally, follow up appointment were recommended for 3-6 months after ADT initiation followed by timed interval depending on tage of di ease. For exampl e, th e with no evidence of meta tatic di ea e were recomm nded to be revi wed in clinical follow up every ix month with a [! cu on evaluation of ymptom , re p n e to tr atment and side effects, digi tal rectal examination and recormnended lab screening. Tho e with meta tatic di ea e should be evaluated as described above, however follow up hould occur every three to ix month . Moreover, it i ugge ted that those with adequate treatment re pon e a PSA of 4 or le , improving ymptoms, and evid ence of psychological coping can be reviewed at longer period such as every six months. Finally, th e G8 screening tool is sugge ted as an adjunct method for evaluating the health status of older adults with prostate cancer. This geriatric creening tool is designed to assess overall health status, with results identifying whether pati ents should receive the arn e treatment as youn ger patients or if patients are vulnerable to impairment thus requiring a more thorough assessment or alteration in treatment. The EAU (20 15 ) also provides guidance for specific laboratory studies based on stage of disease and individual comorbidities. All patients receiving ADT are uggested to undergo both PSA and testosterone screening with each follow up visit. The P A i identified as an important marker for following the course of prostate cancer, as change to PSA levels help identify response to treatment and can also identify complications of treatment. A rise in P A is often seen prior to the onset of clinical symptom by everal months. Testosterone is monitored regularly to ensure patients achieve initial castration goals (< l nmol/L) and to en ure thi level i achieve in order to control di ease progr 1011. patients receiving ADT include a fasting gluco ther reconu11endcd laboratory tests for all and hemoglobin a well as fa ting lipid , 53 both ugge ted to be done at ba eline and then r peat d ev ry three months . Vitamin D and calcium may al o be considered. For tho e with m eta tatic disea e, laboratory creening is also recommended to include h m gl bin cr atinine and alkaline phosphata e. Hemoglobin i reconunended in order to creen for anemia which commonly ccurs after three month of treatment. reatinine is ugge ted to identify i ue related to renal function uch a bladder retention or ureter ob truction while alkaline pho phata e help identify th e livers response to the di ea e proce and treatment. Diagnostic ima ging, in the form of a bone mineral density test i id entifi ed as an important intervention to a e ri k for osteoporo i and thu i sugge ted for all those receiving ADT by the EAU (20 15). Bone mineral density tes tin g is suggested by th e EAU (20 15) to be completed two years after castration and then repea ted annuall y if osteo porosis risk factors or every two years if no risk factors . Finally, for those with a hi story of cardi ova cul ar di sea e or those over the age of 65 years old, consultation with a cardiolo gist prior to ADT initi ation i recommended. Similarly, those with impaired glu cose while on ADT warrants a referral to an endocrinolo gist. Although the EAU (20 15) guideline do es provide som e excell ent recommendations it i incomplete. For example, screening recommendations for physical function , cognition and mood are not specifically id entified . It is only briefly su ggested patient be screened for p ychological coping however su ggestions as to what PCPs are to creen for, such as mood changes, depression or body image concerns are not provided nor are methods or frequency of screening. Other common ly noted symptoms associated with ADT uch as andropau e and e ual dy function are n t addre ed. In utrunary, the guide lines avai lable for P P providing suppm1 to patient with prostate 54 cancer r ceiving ADT are limited. Althou gh orne app ar to be more comprehen ive than other , it i apparent that none of the available guideline creen for all or even half of the documented side effect of ADT. The imp Iiance of bone mineral d nsity te ting wa c n i tently id ntifi ed in all guideline with recommended method f ere ning which i helpful for P P ; however variabilitie in frequency were noted. The remainder of T ide ffect are sporadically and incon i tently addre ed. M reover, the language in which recomm ndation for creening are vague in term of pecific uch a tool and frequency. Interestingly only two of the fiv e guideline recommend p ychological creening, two di cuss screening for exual dy function, two mention cardiova cular creening, one di scus es cognitive changes and only one addre se andropause symptoms. Moving forward , creening recommendation for follow up and ADT related side effect will be presented from four clinical reviews. Clini cal R eviews Clinical reviews are concise, up to date atiicles intended to provid e health care provi ders with updates of recent development and accounts of a specific topic. Reviews aim at providing clinical applications to both primary and secondary care (The BMJ, 20 15). Four clinical reviews will be presented by Saylor et al. (2009), Saylor and Smith (20 13), Wilkinson, Brund age, and Siemens (2008) and Mobile et al. (2009). Saylor et al. (2009) completed a clinical review which focu sed on reviewing the c01runon and recognized side effects of ADT with recommendation for prevention and treatment. Recolllinendations include creening for diabetes, cardiova cular di ease, osteoporosis, and hyperlipidemia and were adapted based on commonly accepted guidelines such as the American Diabetes As ociation (AD ), Am rican Heart A ociation (AHA), National steoporosi oundation (N F) and the Nationa l hole terol Ed ucation Program Adult Treatment Panel III (N P A P Ill) . The authors mphasiz d the lack of 55 evidence ba ed guid line and r earch tudie that~ cu on creening and management of pro tate cancer pati nt receiv ing DT and ugge t thi i related to ADT ha zard bein g relatively n wly identifi d but not fully defined. Bon mineral den ity te ting i rec mm ended for tho e r ceiving m edication in which increa e ne ri k f bone lo , uch a DT, at ba eline prior to initiation of tr atm nt, repeated one y ar after ADT treatment and then every two year or a clinically indi cated. creening D r pre-di ab te or di abete i recomm nded in all tho e receiving ADT, tarting with a ba eline mea urement pri r t initi ation of treatment and then annually. Fa ting pla rna glu co e i the creening te t propo ed, with serum level of 100- 125 mg/dL considered po itive. Hem gl bin Al C i not recommend ed for the di agno is of diabetes in thi review. Fa ting lipoprotein areal o recomm end ed at ba eline, within th e fir t year of ADT treatment and then every five year or a clinically indi cated . Further, recommendations include assigning a target LDL based on cardiova cul ar ri k factors and projected risk category as outlined in the NC P ATP III guideline. According to this guid eline, dete1mining proj ected cardiovascular ri sk involves determining erum fa ting lipid levels, establishing risk based on cardiovascular risk factors and pre ence of atherosclerotic di ease, as well as establishing category of risk with the Framingham risk calculator (National In titute of Health, 2001 ). Based on all this criteria , a LDL target goal i e tablished and interventions such a lifestyle or phatmacologic can then be consi dered. Of note, persistent conce111s have evolved regarding the validi ty and reliability of the ava ilab le cardiova cul ar a e ment tool , including the Framingham ri k asse sment ( ff et al., 20 14 ). However, the tool continue to be upported by a variety of cardiovascu lar organization and guideline to aid in risk di cu ion and de ' i ion making ab ut life tyle and pharmacal gica l preventative intervention ( off eta!., 2014 ). Noticeably ab ent from this clini al revi w i di cu ion or re ommendation regarding phy. ic al 56 functioning, andr pau e ymptom , anemia, ca taract mood change related to aylor and acute kidn ey injury cognitive change or DT. mith (2013) revi wed m etab li e compli cati n of DT, pecifically obe ity, in ulin r i tance, and alterati n in lipid . vi dence r gardin g incid ence of id e effect a well a recommend ed mana g m ent i pr vided. H we er very little is pre ented in regard to creenmg. Author ugge t m ethod of cr ning fi r pre-di abete and diabete ace rding to the Am eri can Diabete A ociati n (AD ) guideline . Diffi ring fr m th e ugge ted interval for creening, a auth r insulin re i tance, thu D guidelin e h wever i th e ugge t tho e receiving ADT to be at hi gh ri sk for ugge t y arly a es m ent via a fa ting pla ma glucose (preferred) or a 2 hour 75 gram oral gluco e tolerance te t for di agno i . La tl y, cree ning and managem ent of lipids ba ed on N EP A TP III guideline i enco ura ged . A third review completed by Wilkinson et al. , (200 ) examined ava ilable re ource for PCPs to provide appropriate follow-up for patients with prostate cancer. It identified the role PCP s have with regard to providing care to this population, but highlights the pauci ty of information regarding fo llow up . Accordingly, a brief overview of the incidence of pro tate cancer in Canada, availabl e treatment modalitie and indication , rec01nmendations for P A monitoring (either during therapy, after primary therapy or during active urveillanc ) and expected PSA respon es to treatment is pre ented . Mo t relevant i the algorithm provided regarding the care for patients with systemic di ease on ADT. !though thi algorithm i not comprehensive it does provide some guidance to P P . Recommendation in lude follow up vi it with family phy ician every ix months in which clinical inquiry, management of treatment related ide effects, and P te ting hould b con idered . Further, bone mineral densit testing i end or ed every two year while n DT and a bone scan if P leveL rise abo\ c 20 nm mL 57 or when linically indicat d . In th fomih and final rev iew, M hil et al. (2009) reviewed the manag m ent of androgen deprivation complicati n in m en with pro tate cane r. Thi r view provid e a detail ed backgr und regarding pr tate cane rand ADT a well a detail d ummary f comm n id e effect to ADT uch a an mia h t fla h , depre i n , exual d y functi n cognitive change , physical function, metabolic yndr m e, cardiova cular di ea and b ne mineral den ity impainnent . ugge tion for creening and mana gem ent are provi ded for a elect group of id e effects. However the creening recommendations pre ented are relatively ambiguou , nonethele an empha i on creening for depre ion, cogniti v change , ph y ical function , metabolic yndrome, ca rdiova cular di ea e and bone min eral densi ty are included . For exampl e, recommendation includ ed in this review simpl y state m en receiving ADT should be creen ed for depression and other m ental h ea lth probl ems, how ever fail to prov id e guidan ce on m ethod or intervals for screening. Slightly more sp ecific are recomm endation for cogniti ve impairment screenin g, which is su ggested ptior to the initiation of ADT and throughout treatment. Although methods of screening are not provi ded for cogniti ve a e sm ent, ratio nal e for creening is highlighted, suggesting regular creening can prov ide va luable information regarding underlying deficits which can negatively impact ca ncer care, outcome , treatment tolerability and patient decision making (Mobile et al. , 2009). For those with pre-existing metaboli c or cardiova cu lar disea e or risk factor for cardiova cular disease, Mohile t al. (2009) ugge t patients b a ses ed prior to th initiation of ADT a well as c n ider referring uch patients to a cardiologi t. Moreover, for tho e with cardiova cu lar di ea e, routine te ting is ugge ted to evaluate worsening of under! ing di , asc. Mean r intervals for a ses ment are not included in the review . 58 Th m t d tailed r c mm ndati n in thi re iew i [! r o t oporo i creening (Mohile et al. , 2009). Recomm ndation includ a full hi t ry and phy ical xamination pri r to tarting ADT t a e for te p ro i , fall and fra ture . urth r mineral den ity via a D XA can 1 r c mmended pri r t cr ning for b n T initiation and then ev ry 6-24 month depending on ri k fa ct r and ba line b ne mm ral den ity. It al o app ar a careful as es ment f overall h alth tatu i recommend ed prior to the initiation f ADT and throu ghout treatment to ' include e ami nati on f d main that could exacerbate pre-exi ting condition and accel rate mortality'' (p. 15) how v r d tail regarding method of exam, tool or frequency are not included (Mohile et al., 2009). In summary, the available clinical review provid e an array of infonnati n regardin g pro tate cancer incidence, preval ence, sid e effect to ADT and sugges ted managem ent of effect but do not lend them elve to comprehensive creening recon1111endations for adver effect of ADT. Similar to clinical practi ce guid elines, some of the above clinical review are more comprehensive than others, although none of the reviews provi de inclusive recommendations for screening of all ADT related sid e effects. Although frequency and interval of creening were variable in the recommendations, half of the review adapted their recommendations from clinical guidelines such as the ADA and the NC P A TP III. The mo t consi tent ere ning recommendation were related to bone mineral den ity, metabolic yndrome and cardiova cular disease, all of which were emphasized to orne degree in three out of th four review . Moreov r, only one review propo d screening recommendations for depre ion, on eli cus impairment screening and ne acldre eel diabete d cognitive creening. The final comp nent of thi chapter wi ll present rcc mmenclation for crcening from an ditorial id ntified during the lit rature earch. 59 Edi torial Medical journal edit rial are h rt aiiicle of th auth r . dit rial pr re id e per p ecti v r e ay that e pre the view and pmwn n a pe ific t pic f intere t, ft n r lated t a arch or review articl publi h d in th e a m journal i u ( teven , 2006) . In thi ca. e, J ne (20 11 ), a co n ultant ph y i ian and end crin logi t relea eel an edi t rial in th e Briti h M edi ca l ciated with Journal eli cu ing th e ca rdiova cular ri hi ghlight th accumulating evi dence t 1 a ugge t DT. hi editorial fu1iher cia ted with adver e ffect n cardiova cular ri k factor , cardiova cular event and po ibl e m rtality. However it i noted that not all tudy re ult concur with the e finding f increa eel ri k f m rbidity and moiiality. It i believed that the a ociation and 1i k of ADT and ca rdiova cular eli ea e will beco me more apparent with time . D e pite th e inconclu ive finding , an advi ory tatem ent from the American Heart A ociation, American ancer ociety and th e men ca n rological As ociati n ha be n released with recomn1endation that all patient receiving trea tm ent with ADT be ee n periodically for follow up assessment of cardiova cular ri k factor , and en ure tho e with preexi ting cardiovascular eli ease have their econdary prevention treatment optimized . Furthe1more, on the basi of the cu n ent evidence and potential for ri k the U F d and Drug Admini tration have m ade ch ange to the label on gonado tropin relea ing h01mone agonist . Recommendations advoca te for P Ps to monit r pati ent for sign and ymptom ugge tive of cardiova cular eli ea e a we ll as the periodi monit ring of blood gluco e or glyc ylated hem globin (U . Food and Drug ociation, 20 l ). The increa eel prevalence of metabolic yndrome and metabolic effect of noted , therefore, patients are recommended periodic foil w up with th ~ir P P.. include a r vi w of cardi va cu lar ri k fa · tors artcr thre ~to si DT arc a! o uggcs tion , month , and th nat least 60 annuall y. Furth r r v1ew f lipid 1 wering tr atment, anti -hyp rten ive m edicati n , gluco e low ring treatment and antiplatel t therapy i indicated wh n appr priate. recommended for tho b ing trea ted with in ulin for di abete a ad and hab igh (2007) a cit d in Jone (20 ll ) id ntifi ed xtra v igil ance i al o a a tud y by Haid r, Ya m, DT m ay negati vely affect glycemic control . ln ummary, the re ear h ha demon trated a lack of clear, c n i tent, comprehen ive recommendation and gu idelin . Avail abl gu id eline and rev iew have attempted to addre creening for adver e effect of DT however rec mmend ati on fo r creening do not m ateri ali ze into a comprehensive guid e fo r P P . Recommend ation are vague in nature, a pecifi c regarding methods of creenin g or frequ ency are either inco n i tentl y provided or not provided at all. Furthermore, all gu id elines and review fail to addre all id e effect including a blatant lack of reconlffiendation for common adverse effects. Thi vari ability in recomm end ati ons likely refl ect the lack of definiti ve evidence available on thi topic (Mclnto h et al. , 2009). What i also apparent from the finding i a lack of uptake or adh erence to the few screenin g recommendation that are available. Finall y, it is id entified that although ind ividu al research studies are focusing on ADT related side effect , very few provide impl ica tio ns for practice with regard to screening which explains the exclusion of a significant number of studie in the literature search. Th e fo ll ow ing chapter will discuss the r search fi nding previou ly analyzed combined with uppl ementary research to info rm evid ence ba ed recomm endation for creening of AD related ide effec ts. 61 hapter Four Di cu sion The re earch de cribed in the Finding que ti n regarding ere ning £ r m en rec 1vmg ynthesize there earch finding in t rm hapter has af£ rd d in ight into the re earch DT £ r pro tat cancer. This chapt r will f curr nt recommend ation for creening prac tice 111 tho e receiving ADT as to what hould be creened, how to ere n, and intervals for creening. Rec01runendation for practice will then be pre en ted based on a consolid ation of the literature and upplemented with evidence ba ed guideline to info rm ugge ti n for creening and care. Recommendations will be organized according to each sid e effect id entifi ed und er the ph ysical, cognitive and psychological health domain. pecific creening strategic and interval of assessment will be propo ed. Futihermore, an overview of rec01runendation will be pre en ted in order to provide PCP s with a quick reference fo r creening fo r this pati ent populati on. T he chapter will fini sh with a bri ef discussion on recommendations fo r education and research. The recommendations below are not intended to replace clinical judgement but rather inf01m practice. Therefore, recomn1end ations should be con idered in conj uncti on with individual patient circumstances. Clinical Practice R ecommendation s To begin, general fo llow up recommendations will be propo ed. Clinical practice recommendations for each physical, cognitive and psychological ide effect will then be presented to include both methods and interva l for screening. Follow up . linical fo llow up is an important aspect of managing patients with can W ith re pect to monitoring men wi th pro tate an r rec iving DT, common obj ctive for foll ow up incl ude m nitoring r ponse to trea tment, en uring complian e with treatment, r. 62 d t cting complication f th rapy, and a e in g and managing palliative ymptom (Mottet et al., 20 15). Howe er, th literature r al recoll1ln ndati n for fi 11 w up in thi patient population are limited and incon i tent. Very fi w re arch tudi e , clinica l practice guid eline review tre the importance of provid r regularly a ing p ati ent or pr po e rec mmendation form th d or frequency f fi 11 w up . Th detailed recommendati n and tre r clinical follow up i ab .. A (20 15) illu trate the mo t lutely mand atory for tho e pre cribing and or managing tho e receiving DT fi r pro tate cancer. It is empha ized that regu lar follow up allow the provid er to a th e pati ent' current condition, check for po ibl e trouble orne ide effi ct to tr atment a w II a ymptom of di ea e, a 'neither bi o logy nor imagin g modaliti e can replac face to face c linic vi it ' ( A , 20 15 , p . 100). Although ome author , uch a Wilkinson et al. (2008) and th e AU (20 15) ugge t pecifi c screening tests to occur during follow up , such as a di gital rectal examination and laboratory te ts, the majority of findings demon trate broad and vague recommendations, such a statem ents that encourage evaluation of ymptoms and side effects of trea tment without providing specifics (EAU, 20 15; Mohile et al., 2009; Wilkinson et al. , 2008). Vague recommendation uch a th ese require PCP to have in depth know ledge of screening for related ide effects and health ri ks in order to as e DT the pati ent properly. Thi limitation leave P Ps guessing as to which side effect to address and how to best screen for the e i ues . As always screening should be individualized, based on age, ymptoms, co-morbidities, treatment modality and progn i ( A , 20 15). !though optimal level for follow up are variable in the literature, ranging from tru·ee to ix months, ba ed on the above finding it is rec mmended patient be reviewed within three month of initiating DT, and then eYer three cam, 20 l ; U, 20 15; Wilkin. on et to ix m nths (A lbe1ia Provincial enitourinary umor 63 al., 2008). During the e fo llow up appointment it i critical that patient be reviewed thoroughly to monitor for di ea e and treatment r lated i ue . pecifically, follow up should include a phy ical exa1nination, creening of ymptom and ide effects a w 11 as laboratory mea urements, all of which are de c1ibed below with detailed recoffilnendation . Phys ical function. creening of phy ical functioning is only briefly mentioned in the literature findings . It is propo ed by thi pap r that thi may be due to the as umption that P Ps frequently screen patient functioning a a basic aspect of appropriate p1imary care. Nonethele s, it is difficult to infer from blanket tatements such a 'careful asse sment of overa ll health tatu s' used in Mobile et al. 's (2009) clini cal review, whether this includ es screening of physical functioning. Mohile et al. (2009) does however provide sli ghtly more specifi c recommendations, suggesting patients be assessed prior to ADT initiation for risks for falls, which one could assume would include measures of functional tatus such as balance and mobility. Regardl ess, the mention of physical assessment without specific recommendations related to intervals or screening methods does not provide PCPs with clear guidance . Interestin gly, By low et al. ' s (2008) study was the only study to investigate the impact of ADT on physical function with a variety of validated and reliable tools; however the study recommendations, did not recommend any of the tools used in the study for the screening of physical functioning in patients on ADT. A functional status assessment, a component of a comprehensive geriatric assessment, i commonly utilized in a variety of settin gs, including the By low eta !. ' s (2008) tudy as well as theN CN (2015b) clinical practice guideline in oncology for older adults . Thi tool will be proposed by this paper as a tool for physical function screening in those receiving ADT . The a essment can be completed via self-reported measures, uch as one's ability to carr out activities of daily living (ADLs) and instrumental a tiviti of daily living (lADLs) or throu gh 64 phy ical p rfi nnanc m a ure uch a th Tim d p and (T fo llowing c mpon nt hould b includ d in the functional tatu a Tabl 3 Functional A sment )tet(N N ,2015b).The f daily li ving (A ): d, gr min g, m bility, ability ind p nd ently and co ntinence. Ability to perform in trum enta l acti viti e of dail y living (IADL ): pr paring m ea l , d ing hou work, h pping, m ana gin g mon ey and u ing the tel eph ne. Performanc tatus: via Ka1nof: ky or (http ://oncologypr .e m o.o rg/ uid eline Practice/Practice-Tools/Performance- cale ) Fall : A e for falls in th e Ia t 6 months or fear of falling. For tho e who have exp rienced a recent fall (within 6 month ) or have a fear of falling, consider additional evaluation with : • Physiotherap y or occupational therap y as es ment • Assess Gait us ing the TUG test (see CCN, 20 15b for test specifi cs) • Checking and replacing Vitamin D level when appropriate • Refer to geriatric (N CN, 20 15b). Idea ll y a functional status assessm ent would be done by th e onco logist or urologi t during the dia gno tic and treatment planning process, regardle P P should con ider a ba elin functi nal tatus asses ment and repea t thi s a sessment through ut treatment in order to identify change t phy ica l statu or functioning . Interva l f ere ning hould be ba ed on the patient , · age, co-morbiditie and vera ll hea lth tatus, ideally occu lTing at I a t ever 6-1 ~ month .. Moreover, a full functional a ment i not alway. required a. a brief s · reen ing or phy, ical and 65 fun tiona! abilitie can c ur durin g regular follow up vi it by ob erving mobility and ga it a the pati nt mo e thr ughout th lini c e am r 111 . Metabolic disea e and diabete . creening il r in ulin re i tance and diabete included a a r comn1endati n in m any clinical practi ce guid elin , clinical review and ind ependent re arch tudi e ba d n ignificant ev id enc th at DT increa e in ulin re i tance and therefore incidence f diab te . T ai et al. (20 15), ociati on ( (20 13) all refer to th e American Di abete rec01nmendation with regard to method authors differ from AD ayl r et al. (20 13 ), and guid eline and from each oth er. A D A gu ideline years and tho e with ri k fac tor mith ) guideline for th eir f creening, however interval pr p intervals ba ed on lev 1of ri k, for exampl e th ayl rand ed by the e uggest creenin g w ithout ri k factor be creened every three hould be screened more frequ entl y. Currentl y, DT or hypogonadism is not noted to be a risk fact r for diabet s in the ADA guidelines, but it appears the majority of stud y author , including Tsai et al. (20 15), aylor et al. (20 13 ), and aylor and Smith (20 13) consider the risk to be high eno ugh to pur ue more frequent screening. Moreover, the majority of tudies anticipate diabetes or insulin re istance a a potential issue by recommending ba eline creening in the form of laboratory work be considered in all patient prior to A DT initiation. As n ted above, the majority of re earch article on thi topic adapt their cr emn g recommendation from the ADA, however, a thi paper serve to infom1 care delivered by P P within anada , anadian guide lines from th anadian Diabete A ociation (CD ) will b pre ented . Ba ed on th increa ed risk demonstrated in th literature, tho e und ergoing ADT fo r prostate cancer with or wi thout other ri k factor initiation and repeated annua ll y. Method of hould und ergo screening prior to DT reening hould include a fa ting pi a ma g lucose 66 ( P ) or h mo gl bin A1 Additi nally, ri k fa ct r :D r di ab te ee th e DA guid lin fr m h uld b a e ed pri r to DT and r peated annu ally, imply ba ed nth dia gno tic criteria noted old enb erg and Punthakee (20 1 ) ab v . M ea urem nt obtained at ba ld nberg, 201 ). koe t al. (2 0 13) :D r p cifi c ri k fa ctor . The a e ment fi r m etab lie yndr m i by m , Prebtani & ( k e, Punthak e Ran line and repeat d w ith ach :D 11 w up a uch a blood pre ure hould be ment. ther mea urem ent uch a wai t circumference hould be btain d ideall y at ba el ine and at lea t annu ally in ord er to monitor chang and adequ ately a e ri k. FUiiherm re interval for creening hould foll ow the above recommend ati on fo r in sulin re i tance that recomm end yearl y creening w ith either a FPG and/or A1 . Fa ting lipid creenin g reco mm end ation will be di scu ed below and hould be impl em ented for thi patient popul ati on. Cardiovascular di sease. T here is accumulating evid ence to ugge t ADT can negati ve ly impact ones cardiovascul ar health. The con·e!ati on between ADT and cardi ova cul ar di ea e i uggested to be related to effect on varying cardi ova cul ar ri k fac tors impacting the likelihood of card iovascular events and possible motia lity (Jones, 20 11 ). As Jones (20 11 ) hi ghli ght however, there is no con en us that tlli as ociation trul y exists, however in li ght of the potential for increased morbidity and mortality, consideration of cardi ovascul ar health i recomm end ed in a mall minority of cl inical practice guideline and reviews ( A , 20 15, Jone , 20 11 ; Mobile et al. , 2009; aylor et al. , 2009; Saylor & mith, 20 13 ). Otherwise, creeni ng recomm endation with regard to ADT and it assoc iation with cardiovascul ar hea lth are o mewhat li mited in the literature, pa1iicul arl y in indi vidu al re ea rch tudi e . P tenti al trategies to minimizing morbidity and mortality incl ude a hared care approach between P P and p c iali ts. For exampl e, P P , hould routi n -ly a scss patient. for 67 cardiova cular ri k fact r , monitor for ign and ympt m f ca rdi va cular di a e, revi w cunent cardiova cular treatment , and refer or con ult when pre-exi ting di ea e or c ncen1 are id ntifi d ( A , 20 15 ; J n , 2011 ; M hile et al. , 2009) . It i anticipated that with time and furth er r earch, new data will guide cardi va cul ar cr ening rec mm ndation for tho e receiv ing ADT. In the meantim , the litera ture i not c nclu ive a t whether creening trategie for the pro tate cancer popul ati n rcc iving population (N N, 20 l5a) . A DT hould differ for th e g n ral uch th e premi e of the maj rity f availabl e reco mm ndation tern from theN EPA TP III guideline which are di cu ed in detail in th e findings, which focu e on identifying and categorizing ri k and dy lipid emia creening and m ana gem ent ( aylor et al. , 2009; aylor and mith 20 13 ). What remain unc lear is how oft n creenm g should occur, as this vari e between stud y recommend ati on . Anderson et al. (20 13 ), authors of the m ost recent anadi an ardiova cu!ar Society (CCS) guidelines provide recommendation that are clo ely ali gned w ith the NCEP A TP III guidelines referen ced by m any of there earch fi ndin gs in the literature. A uch, the guidelines will provide the basis for cardiovascul ar screening recon11nendation in thi paper. Screening should begin w ith a hi tory and ph ys ica l exa minati on, id ea ll y completed prior to ADT initiation and then routinely asses ed durin g follow up as previously de cribed. T he hi tory should include screenin g for cardiovascular ri sk fa ctors such a : moking, diabete , hyp rten ion, family hi story of hyp erlipid emia or prem ature cardiovascular di ea e, chroni c kidn y di ease, inflammatory bowel di ea e, HIV, PO, abdomina l an ury m , erectil e dysfunction and obe ity (BM I > 27) (And er on et al., 201 3 ). Ph ys ica l examination hould ai m to identif clinical ev id ence of athero clero is and r hyp erlipid emi a and includ an ocular, cardiova, cular, arotid, respirat ry and abdomina l exa mination ( nd er on et a!., 20 13 ). 68 xt, btaining ba elin lab ratory m a ur m nt , uch a renal function ( FR) i r c mmended . DL HDL, triglyc rid , gluco e and nee thi data i obtained the P P can calculate the patient cardiova cular ri k core via the Framingham ri k c re calculator, which determine the patient lev 1 of ri k int three categ ri e I w, interm edi ate and high ri k for (http :/lwww .cc .ca/imag I uid eline IT ol and alculat r V di ea e n/Lipid _ ui_201 2_FR _ ol_ EN .pdf#page= l&zoom=aut ,- 1 9,540) . Thi ri k a e m ent h lp to illu trate whi ch patient would mo t likely benefit from primary preventi on trategie of hyperten ion and dy lipid emia (Ander uch a pharm aco logical treatment n et a!. , 201 3). Interval fo r creening are propo ed based on Framingham ri sk core, and includ e ere nin g a above every thr e to fi ve year if Framingham ri sk score is und er 5% and annu all y if core is above 5% (Anderson et al. , 201 3 ). A ndropau se. The finding dem onstrate the sympt m of andropau e, uch a hot Oa he , ni ght sweats, gynecoma tia, loss of libido and sexual dy fun ction are common, imm di ate and bothersom e side effects to ADT. However, creenin g recommend ations are infrequ entl y emphasized in the literature. For example, literature findings fa il ed to present any screening recommendation fo r hot fl ashe or ni ght sweats. Mo reover, gynecom astia wa bri efl y mentioned in one of the five clinical practice guid elines, with a foc us on earl y a e ment and treatment wi th radi ati on therapy if necessary and de ired (NI E, 20 14 ). This suggests to the rea der that thi group of ide effect is either entirely known to P P and therefore require littl attention in creening recommendation or the e side effect are impl y common and as umed outcome f trea tment therefo re requir littl e focu by P P . urp ri ingly, only four of the twenty- two paper fro m the li terature review acknow ledged andro pause ymptom with suppl emental reco mmend at ions. f the e fo ur paper , the mo t commonly defined mptom is ex ual dy fun cti on. lntere tingly, men in freq uentl y di clo ed se ual ide eCCccts with P Ps that 69 lik ly c ntribut to th large gr up of m en that w re 1 ft untreated for thi de ire tore ume exual activity ( runfeld tal. , 20 12). function are m chan g ide ef[i ct de pite !though anticipat d change to exual t conunonly related to depl tion of te to teron , it i al o e entia! to anticipate to libido, exual re p n e and intimate r lati n hip du t impaired p ercepti n of bod y image, ma culinity and exual attracti vene (Harringt n et al. , 2009) . Ba d n the e findin g it becom e evident that P P pl ay an e enti a! rol in en uring pati ent wh de ire ex ual activity and intimacy are creened appr pri ately and pr vided the nece ary treatm ent option pharmacological agent and c un uch as !ling ( nmD ld t a!. , 20 12) . As specific id e eU ct and their treatment are expected to occur at pecific point in ADT treatment, P P must en ure the appropriat ide effect are being routinely creened. For example, treatment with radi ation therapy o r Tamoxifen may be offered for gynecoma tia which occurs within one to three month of treatment initiation, th erefore creening for thi condition must occur at the first follow up appointm ent after starting ADT (N ICE, 2014 ). Similarly, exual function should be screened regularly in order to identify the i ue a early a possible to ensure the appropriate suppot1 and treatment i offered . Thu . . creemng IS recomn1ended at regular intervals tlu·oughout treatment, beginning at the first follow up appointment after ADT initiation (NCCN, 2015c) . Those with identified i ue hould then undergo a more thorough evaluation, which hould includ e p ychosocial i ue , uch a depre ion, impaired body image, relation hip problem , or ther contributing fa ctor dru gs or alcohol (N N , 20 15a; N uch a N, 2015c) . La tly, a phy ical e amination hould be considered in those wi th exual dy function, with a focu on the che t for gynecoma sti a, abdomen, phallu , cr tum and tc ti le , and the cardiova scular ys tcm (N N, ~0 15c ). hi paper recommend the u e of validated tool s to a es, for andropause , ympto m. , 70 uch a the Distre Thermometer (DT) (http: //www .nccn.org/profe ional /physician_ gls/pdf /senior.pdf) and the exual Inventory for Men ( HIM) (http ://www .auan t.org/ed ucation/erectile -dy functi n.cfm). Neither tool were included or reco1m11ended in the tudy finding for creening, however both have demon trated validity and reliability for creening in cancer patients (Cappelleri & Ro en, 2005; , 2015c) . The DT tool i quit inclusive and addre es many of the cmmnon ide effect to ADT, including exual dy function. This tool can be completed prior to appointment , aving time a P P can simply refer to the identified issue , or can be u ed to prompt P P to asses pecific ide effect . More pecific to exual health i the SHIM, which i recommended by the (2015c) and ub equently thi paper. Thi hort screening tool screens for erectile dysfunction and tho e who may benefit from treatm ent for this condition (NCCN, 20 15c). Anemia. The conelation between anemia and both cancer and ADT is well e tablished in the literature (Curtis et al., 2008; Dicatol et al., 201 0) . Despite this as ociation, very little information was found in the literature with regard to screening or ymptom asses ment. This is an important gap as symptoms associated with anemia, such as fatigue and dyspnea (Curti s et al., 2008), should be a consideration when it comes to symptom assessment and management. Nonetheless, screening is only reconunend ed by two studies via a hemoglobin measurement (Curtis et al. , 2008; AU, 20 15). Consequently, ba eline laboratory investigation via a hemoglobin or hematology panel should be considered in order to trend hemoglobin va lu e with the initiation and or long tem1 treatment with ADT. As the literature demon trate anemia an occur within three to six month of ADT initi ation , therefore repeating r emng v1a a hem globin would be appropriate at that time or sooner if clini ally indicated . creenin g interval should depend on clinical presentation and symptom a w II as con ideration of co- 71 morbiditie . Co-morbiditie , uch a impaired kidn y function , coagulation disorder , nutritional in ufficiencies and inflammatory di ea e hould be con id red a a c ntributing factor to an mia and may change interval for creening (Dicatol et al., 20 10) . Cataracts. Regrettably, re earch finding failed to produce any literature with recomm endation related to catarac t creening or y xaminati n in general. Thi limitation is likely related to cataract being a new defined id e effect to ADT. How ever, for the sake of comprehen ivene , g neral reconunendations deri ved fro m the (CO ) are provided to help guide P P in providing care. anadian phthalmic Society (2007) recommend regu lar ocular exams in the adult population, with interval depending on risk and age. High risk pati ents include those with diabetes, and family history of ocular conditi ons such as cataracts. Although ADT is not currently a do cumented ri sk fac tors id entifi ed by the OS , given the potenti al for increased risk of cataracts with this treatment regimen it is sugges ted that those receiving ADT be considered to be at higher risk and therefore pursue screening more frequentl y. Therefore, a recommended by the COS (2007) , those who are asymptomatic and receiving ADT hould undergo screening at least every two yea rs for tho e over the age of 50 and annuall y fo r those over the age of 60. Patients who identify visual changes such as impaired visual acuity, visual fields, color visions or physical changes to the eye should be examined as soon as poss ibl e by an eye specialist (COS, 2007). Bone mineral density impairment. The most consistent recommendation for screening in men with prostate cancer receiving ADT appears to be bone mineral density te ting. ll five clinical practice guidelines provide some form of rec01nmendation as do the majority of the clinical reviews, however th re are incon i tencies noted in initiation of creening, frequency and intervals. or the most part, the majority o[ r commendations uniforml y propos ba ~ lin e bone 72 mineral den ity cr ning pri r to the initiati n f Mohile et al. 2009; Wilkin anc r Network, 20 10; net al. , 200 ). While interval and frequ ncy f creening ar variable, with recommendati n varying from n two year DT ( u tralian ugge tion revery 6-24 month re pectively ( u tralian 2009; ayl ret al. , 2009, Wilkin n frequency, to annually, t very anc r N tw rk, 201 0; M hil e et al., n et a!., 200 ). What remain c n i tenth wever i the ugge ted meth d of a e m nt for bone mineral den ity, with the u e of the World Health rganization FRAX tool along ide a D X author can . lth ugh mall variation do exi t a ugge t FRAX in conjunction with D XA can (Alberta Prov incial Team,2013 ; Al- ham ietal. ,2012)whil eother which starts with the le orne enitourinary Tumor ugge ta tepwi seapproacht cr enm g inva ive FRAX and propo e DEXA if ri k i id entified by th e FRAX (NCCN, 2014). lntere tingly only one study with a focus on impaired bone mineral density recommend ed a history and physical asses ment for those on ADT in order to identify ri k factor for osteoporosis. Although the FRAX a es ment do es require data gathering through a focu ed history in order to obtain infonnation for osteoporo i ri k, it doe not cover other avenues that would suggest risk, such as physical and functional decl ine. A uch, what then become glaringly absent in many of the osteoporosi and fracture ri k as e ment recommendation ts an as e ment of physical function, uch as mobility, bal ance and gai t a impairmen t in the e area may increase ones usceptibility for falls and thu s fractures . ther tudi e h wever, uch a Bylaw et a!. (2008) and Mohile et a!. (2009) link alter d phy ical function uch a impaired balance and strength with risk for fall and fracture and usc thi ~ information to prcmi e creening recommendati n . N nethele , the litera ture supports crccnin g bone mineral density. In ·onsist ~n ·ic , 73 however do not lend for traightforward recommendation , therefore clinical prac tice guid lines from 0 teoporosis anada , by Papaioannou et al. (2 0 l 0) will be propo ed for osteoporosis and fra cture ri k creening in thi paper. A screening all men undergoing uch, recommendations will begin with empha i on DT regardle of age. This should includ e an initial bone mineral density a se ment via a DE focu ed hi story, phy ical exam in ation and FRAX a sessment (http ://www .rheumatology.org/IAm-A/Rheumatologi t/Re em·ch/ linician-R earchers/Fracture-Ri sk-A sessment-Tool-FRAX) (Papaioannou et al. , 20 10) . Bone mineral den ity te ting hould be repeated annually while undergoing ADT, pa1iicul arly if treatment fo r o teoporosi would be acceptable to the pati ent. However, if the pati ent would not consider phannacological treatment fo r osteoporosis one should consider the nece sity fo r bone mineral den ity testing. Acute kidn ey injury. Similar to cataracts, acute kidney inj ury app ears to be a relatively new ly defined side effect to ADT as there is very littl e data availabl e describing this is ue. The studies that are cunently available propose fmi her research to investi gate the clinical impOiiance of this side effect (La pi et al. , 20 13). Consequ ently, of the available research studie identifying this side effect, screening rec01mnendations are not provid ed, therefo re thi ide effect wa not defined in this paper ' s fi ndings. In light of the sugge ted association between ADT and acute inj ury and the imp act prostate cancer itself can have on renal fu ncti on, it is reasonabl e to screen for kidney function periodi call y throughout treatment. Interva ls for cree ni ng hould depend on pati ent' s age, condition, presence of co-morbiditie and phannacological agents pre cribed. Screening fo r kidn ey fun ction via a creatinine and or glom erular fi ltration rate (G R) hould be add ed to other regular screening laboratory work such a hematology paneL fas ting gluco e or li pid and be 74 done at 1 a t annually. mg p cific m dicati n that ar p tentiall y nephrotoxic r tho n or have c m rbid conditi n con ider d mor frequ ntly uch a very thr ri k frenal i ue , creenmg h uld be t ix m nth . Cogniti ve impairm ent. M hile et al. (2 009) acknowledge th impact cognitive impaim1ent can hav n cancer pati nt , p tentiall y nega ti v ly impacting cancer ca r outcome , treatment t lerability and pati nt de i i n-making. De pite thi id entified va lu e in creenin g and potential for identifying underlying c gnitive i ue , very few finding recomm nded uch creening. Mohile et al. (2009) and M hi! tal. (20 10) both advocate for ere nin g for cognitive impairment prior to the initiation of ADT in order to identify those with und erlying cogniti ve defi cits in which treatm ent ma y be offered or require further monitoring. Moreover, cognitive creening wa particularl y empha ized for tho eat higher risk of developing co ndition uch a dementia (Mohile et al., 201 0). Unfortunately, a guide or tool was not provided in the literature findings. Although study findings present evid ence to supp ort screening for cognitive impainnen t in som e patients with prostate cancer receiving ADT, very lit1l e evid ence was availab le to upport initiation, m ethod or intervals of cognitive impai1ment creening. onsequentl y, further evidence was sou ght from the literature in order to provide concrete recommendation . While Mohile et al. (2009) and Mohile et al. (20 10) recommend all patient be creen d for cognitive impairment, current evidence suggest that screening for c gni ti ve i sue in tho e without ympt m of impairment in in uffi cient (U . Preventative ervice Ta k For e, 2014 ). However, cognitive creening is upported if patient , family or P P identify ign and ymptom f impairment (N N, 20 15b; U. Preventative ervi ·e Task Force, ~ 0 14 ). Tho c with identified impaitment should be ere n d for potentially re cr ·iblc or contributing ractors 75 to cognitive impairment u uch a medicati n , moti nal di turbance , co-morbiditie , ub tanc , and ymptom burd n h uld be done by th P P (N , 20 15b ). Additi nally que tioning clarifying the nature f impairment i r c mmend ed . N xampl p ecific pro vid ed by the N(2015b)includ: Table 4 Screen in Question to A, es ognitiv Impairment in anc r Patient 7 Do you have diffi culty payin g attenti n? Do yo u have di ffic ulty multita king? D you fr qu ntl y leave ta k inc mpl ete? Do you have di ffic ulty findin g word ? D yo u h ave di fficulty remembering thin g ? Do yo u need to use m ore prompt to remember thing ? Does it take yo u longer to think through pro bl m ? Do yo u notice an impact on functional p erformance? Job p erformance? If cognitive creenin g is required due to identified impairments, P Ps should co ntinu e to monitor signs and ymptom throughou t treatment to monitor for progression and or offer appropri ate treatment. Finally, a neurological examination may al o be indicated, in whi ch additional assessment or imaging may be indicated if focal neurology defect are noted (NCC , 2015b) . A refeiTal to neuropsychology may also be considered (N N, 20 l 5b) . Depression and distress. Based on overa ll prevalence of depression in the general cancer population in conjunction with risks associated with ADT it seem practical to creen for depre sion in this patient population, however the literature provide littl e recommendation . For example, Mohile et al. (2009) empha ize creening ford pre i nand oth r m ental health i ue , whi le Pirl et al. (2002) sugge t ' appropriate and re gular' a e mcnt or mood. and Lee et a!. (20 14) advi e th e identification and treatm nt of d press ion hould b a priority. The Au tralian anc r Network (20 l 0) provide equally ambi guou, ' Oun I, uggcsting hea lth 76 i nal be aware of the ri k fa ctor for an i ty and d pre i nand be pr pared to treat appropriately. Method for In order t r ening and to 1 are not u gg t d by any of the finding . upport pati ent with appropri ate m ntal health erv ice for di tre need to identify th i ue. Ideall y pati nt notify their P P about mental h alth i u f i ue and c ncem or P P ask regularl y, how ver, ti gm a and tim e con traint often tifl e di cu wn regarding mental health i ue ( rate betw een pati ent the P P N , 20 15d). If-report of di tre v ral tudi e have id entifi ed low conco rdance or mood alterati on with th at f phy ician clinica l impre ion , which support th e u e f tandardi zed validated tool for mea uring p ychol gical is ues in tho e with cancer (Litof ky et al. , 2004; ollner, Dev ri es, & teixner, 2001 as cited in N CN 2015d). What become more complica ted i recommend ations for what pecific tool to use. There are a vari ety of systematic reviews and individu al research studi es examining the u e of the vari ed validated screening too ls avail able with very littl e co nsen u on the ideal tool but an overall consensu doe exist fo r the need and importance of screening (Au stra li an Cane r Network, 20 10; Lee et al. , 20 14; M obile et al. , 2009; Pirl et al. , 2002) . T herefore, this paper recommends the adoption of cunent psychological screening too ls recommend ed by one cun ent facility or as fo llows. The NC N (20 15d) guidelines for survivorship, w hich fo cu es on the late effects and long tenn psychosocial and phy ical pro blem a ociated wi th cancer and it treatm ents recommend either the PHQ9 or PHQ2 as valida ted as e ment tool for depre ion in the cane r survivor popu lation (doi : I 0. 1046/j .1525- 1497.200 1.016009606 . ). The pati ent hea lth que tionnaire (PH ) i a clf-admini ter d dia gno tic instrument for criteri a ba ed di ag no ' i , of menta l health di ord er such a dcpres ion (Kroenke, pitz r, ' Willi ams, 200 1). T h , PH Q9 77 con i ts of nin crit ria upon which depre ion i dia gn di order (Kro nke et al. , 2001 ). ed ba ed n the D M -IV depr imilarly, th PH 2 c n i t of 2 qu 1ve tion to creen for depre ion in which if c re are high for depre i n, additi nal qu tion mu t be a ked to e tabli h diagno tic criteria (Kroenke et al., 2001) . The b nefit e t ol i dia gn validity, with the ability to both dia gn 2001 ). It application to the fth tic e and grad e the everity f depre i n (Kroenke et al., DT populati n relate t parall el i ue faced by the ADT and urvivor hip p pulati n, uch a d pre ion, b dy image i ue , exual dy fun cti on and c gnitive impairment. Therefore the e tool ma y prove helpful when a e ing form d in th e pro tate cancer populati n receiving ADT. TheN N (20 15d) al o recommends u sing the Di tre Thermometer (DT) and accompanying 36 item problem li st as an initial screenin g tool for cancer related di stress. Thi tool identifie the pre ence and level of distress as well a ource uch as practi cal, family, emotional, piritual and physical iss ues related to cancer and its treatments (http ://www.nccn .org /professional /physician_gl /pdf/senior. pdf) . Thi validated screening tool was developed specifically for cancer patients and ha demon trated good en iti vity and specificity, a well as good con-elation with other p ychological tool scale (N uch as the Ho pi tal nxiety and Depre ion N, 20 15d) . Mitchell, Kaar, Coggan and Herdman (2008) note it wa deemed acceptable to 75% of clinicians when used (as cited in NCCN, 2015d) . A lthough thi tool doe not singularly screen for psychological conditions uch a d pres ion, it allows for a broad creen for cancer trea tment related effects that can influence psychological health . Moreo r, a this to 1 screen for a variety of side effect , it u e may eliminate the need to complete a vari ty of scr ening tool for each component f health, su h a phy i al, cognitive and r s ·hological. 78 Altered bod y ima ge and lo s of masculini ty. For a large majority of men r ceiving ADT for pro tate cancer, ide ef:fl ct do not occur in i olation . Many of the ab v id e effect can directly or indir ctly impact ther area of health and well -being. For example, change to physical appearance DT related uch a gyn c m a tia and exual dy function w re id entifi ed to significantly impact m en' percepti on of ma cui in ity, attrac ti vene and body im age ( run feld et al. , 201 2 · Hanington et al. , 2009) . M ore ver, in ord er to provid e patient centered, holistic care, P P need to con id er the impact the e changes to body image and m a culinity m ay have on m en and their quali ty of life . The literature ha ugg ted a po ibl e connecti on between change to physical appearance w ith depres ive symptomology, which may be related to alterati ons in self-e teem and the impact of side effects on intimate relationships (H anington et al. , 2009; Lee et al. , 20 14). Therefore, PCP must anticip ate changes to psychological health and thu s creen earl y and frequently, startin g at the first fo llow up appointment in ord er to support, edu cate and treat appropriately. As identified in stud y finding , patient and PCPs may be reluctant to openl y discuss these issues du e to embarrassm ent or discomfort , therefo re the use of a screening tool, such as the Body Image Scale (http ://tools.farmacologiaclinica.info/index .php ), which is pecific to body image changes related to cancer, or the DT m ay be indica ted to id entify those with altered body image (http ://www .nccn.org/profess ionals/physician_ gls/pdf/senior.pdf) (Harrington et al. , 2009; N CN, 2015d). omprehensive recommend ation have been developed to support PCP with creemng men with prosta te cancer receiving ADT. Proposed screening recomm endations were deve loped based on the above re ea rch fi nding and supplem ntal evi dence described in the literature. Recommend ation included both method and int rva l for scr cning a vari ty o f physica l, cognitive and psychological sid e effects to ADT. In light of tim on traints noted in primary 79 care, a ne page umn1ary of creening r commendation wa d veloped to provid e a quick reference for PCP providing care to thi patient population, which i provided below . The final component of thi chapter will di cu implication for practice, uch as patient and P P edu cation need and fmiher re arch requirements. 80 Table 5 Sum.mary of lini al Pra cti Health Domain Impair d phy ical function M etabolic R omm ndation R commendation -Fun - alculate Framingh am ri k core. -Laboratory creening: LDL, H L, tr1 glycerid gluco e and FR -Phy ical examination Andropau e Anemia Cataracts Impaired bone mineral density Acute kidney Int rval -Phy ical exam pati ent for gyn ecoma tia -Inquire about hot fla he and ni ght weat . - exual dysfunction creen throu gh inquiry or u e of a screening tool uch a the DT or HIM . -If exual dysfunction , exam phallu , scrotum and testicles, and the cardiovascular y tern (N N, 20 15b). -Laboratory studie to include a hematology panel or hemoglobin. -General eye examination by an ophthalmologist. -DEXA scan and fracture risk assessment based on a history, phys ical and FRAX assessment tool. -Laboratory a e sment (creatinine, GFR) . DT initiation and then -Pri r t annually. - P every 3-6 month . -Ba eJine lab prior to ADT and then at lea t annual ly if Framingham ri k score > 5% -Phy ical exa mination every 3-6 m nth . initiation . -H t fla hes, ni ght swea ts and exual dy function should be a e ed at first follow up appointment after DT initiati on (within 3 months) and th en every 3-6 month ). -Prior to ADT, repeat within 3-6 m onth , then at least annually. - very 2 years > 50 and annu all y for tho e >60 years old . -Ba eline D XA/FRAX and repea t annuall y. ognitive impairment -Screen for potentially reversib le/contributing factors . ons id er neurological examination or re[i nal to neurop ycholo gy. -A se s if patients, family or P P identify sign and ymptom of impairment. -PHQ9/PH 2 or the DT - very 3-6 months . dy ]mage rna culinity - , s within 3 month mitiation and repeat C\' Cr months. 81 Recommendation for Education Finding have al demon trated gap in b th pati nt and P P know! dg and education regarding ide efD ct and ere ning requir ment ~ r DT, b th f which impact ca re. xampl , evera l tudi e have d m n trated that awarene ignificantly am ng t patient , a cau e or de cribed urpri of conllTion r DT ide ef~ ct varied m patient attribut d ef:D ct to e ither age or unknown when ympt m ar e ( runfeld et al., 20 12; M hi le et al., 201 0) . Furthermore, de pite guideline and in.G nnation regarding p cifi c adver e effect , uch a bone lo sand ADT, overall kn wl dge, percepti n f u ceptibility and engagem ent in preventative behaviour wa demon trated to be low v rail (Nadler eta!. , 2013 ). In addition to gap m patient education identified in th literature, it i al o noted that pati ent are frequentl y dissati sfied with the education they received fr m health care provid ers (Chapman & Ru h, 2003 as cited in In titute of Medicine, 2008). Based on the e finding it i evid ent that pati ents would benefit from an open di cu sion with specific and clear evidence ba ed edu cation rega rding ADT and its side effect (Nadler et al., 2013) . Further, through providing thi edu cation pati en ts will better und erstand reasoning for creening which may influ ence uptake. Screening it elf provides an important opportunity as it ma y lead to pati nt eeki ng further knowledge regarding side effects and provides an entry point for di cu ion and ed ucation from P Ps (Nadler et al. , 20 13 ). In order to increa e th e uptake of infonnation, two things should be considered. Fir t, adequately managi ng ide ffect to illne , uch a an iety or pain may be u eful with comprehension and sati sfac ti on wi th information pro ided ( hapman & Ru h, 2003 as c ited in In titute of M edi cin , 200 ). econd ly, information should b tailored to each individual, ba -d on edu cati on, clini al ituation, diagnosi , e p (In titute of Medi ci n , 2008). ore am pl , tation and pre ferences me prefer very detailed information whil e oth ers 82 detai l but pr fer infi nnation be pr vided nan a needed ba i (In titute of M dicine pre£ r 1 200 ). Finally, in£ nnati n need chang thr ugh the di ea hould be offer d regularly (In titut traj ct ry, therefore inf01mation f M edi cine, 200 ). imilarly, P P' al or quir m r educati o n r ga rdin g c reenin g requir m e nt fo rth receiving DT for pro tate cane r. Thi commonly defin ed ide effect to demon trated by th p or uptake of creening for DT uch a impaired b ne min eral density a well as pati nt uncertainty of ide effect ( 1- ham i et al. , 20 12; hapman & Ru h , 200 a cited in In titute of Medicine, 200 ). Poor uptake in creening prac ti ce and pati ent edu ca ti n i likely multifaceted , including limited clinica l practi ce guid e lines, P P un certainty about current practice and guidelines, a lack of edu cation r garding the u efuln s and application of creening tools, and an overall lack of educa tion of the impact of id e effect and th ir co n equence on overall health and well-being (Al- hamsi et al. , 20 12). Thus, it tand to rea on that the development and di tribution of compreh ensive guidelines would prov ide P P with the supp ort and education required to provid e appropriate ca re for those with prostate cancer receivin g ADT. Consequently, consolidating current evid ence and pur uing gaps in re earch to develop one comprehensive document should remain a focus for researchers and profe ional o rganiza tion . Consequ entl y, edu cation, further research and guid e lin e development is r quired . ducation must be targeted to tho se prescribing and mana ging th e care of tho eo n P Ps in order to increa e screening and redu ce DT, uch a DT as ocia ted morbidity ( libha i et a!., 20 12) . Id eally, thi education would be in the form of co mprehensive guid e lin e~ , how ever in th e interim regular educa ti n session and appropriate di emination of information that focu es on current evidence and clini cal practi ce guid e lines related t 20 15). AI- hamsi eta!. (20 12 ) noted som e , u ce reenin g ma y be u 'eful (Tomasone et al., with profc s iona l group workshops in 83 increa ing P P know l dge of cr ening foro t p r i and the id ntifica ti n of ri k factor in a 2008 tud y, and ugge t imp ! m ntati on f imi lar du cati n initi ati e for P and NP . h goal of the e initiative w uld b t in crea e P P ' kn w l dge rega rdin g id e ef[i cl the benefit and recommend ati n fi r creening, and the importance of di f ADT, minating thi informati n t pati nt . M or over, enc uraging c ordin at d and harcd care betw en P P and oncologi t hould be con id er d, a thi w uld all w fi r P P t u e the o ncologi t a a upportive re ource and con ult a needed w ith rega rd to ide effect m anagem ent ( T creening recomm nd ati n or '20 15b). Recommendation for Research Finall y, a aylor t al. (2009) indicate om e of th e DT related sid e effects are new ly identified and therefore not full y defined . Thi sugge l fu rth er research into the id e effects of ADT in order to adequately develop evidence ba ed creen in g recommend ati on and guide line . Moreover, it m ay be beneficial to focus research on the younger prosta te cancer po pul ati on as this m ay potentially identify new them e or hi ghli ght side effects that may be m ore likely to occur or cause distress compared to m en in an older coh011. imilar i ue were va lidated in previous brea t cancer studi es which dem onstrated ignifica ntl y more di tress regarding body perception in younger pop ul ati ons (H an ington et al. , 2009) . Such findings w ill all ow for greater support to this patient popul ation . 84 onclu ion Th r arch qu e ti n , for P pra ti ing in a ptimary care required to identify ide effi ct in m n with pr tate cancer r c iving literature revi w . In order t an wer thi qu e ti n th literature wa uch a the chrane library, tting, what ere nin g i DT wa xpl red in thi earch throu gh a variety of HL, Pubmed and Joanna Brigg In titute Library a well a th grey literature. Thr ugh vati u c mbinati n f arch term and th e application of inclu ion and exclu ion criteria, a t tal of 22 article were elected that were pertinent to the re earch que ti n. There earch finding demon trated few clinical practi ce guid elin e that pre ent recommendation for creening for DT related ide effect . M reover, th e guid eline that are available lack con i tent and comprehen ive recommend ations for creening. on equ entl y, without guidelines to upport primary care practice and aid deci ion makin g, P P do not ha ve the mean to adequately support thi patient population. A vari ety of other is ues has pre ented baiTiers to PCP s screening patients appropriately, such as a lack of know ledge, time con traints and provider di scomfort addre ing specific adverse effect . Pati ents too have demonstrated a lack of awareness of ADT side effects which ma y limit their probability to report ide effect to their P P . Finally, althou gh there is an abundanc of literature regarding ide effect to ADT, new adverse effects are being identifi ed in the literature, ca lling fi r further re earch into pecific risks of treatment. Through an integrative review of the literature, current recomm ndation , method and interval of creenin g were reviewed . Recommendation for practic ha e been pre, en ted based n a con olid ati on of the e finding in conjun tion with other evidcnc ba ed guid elines. pecific recommendati n include regular clinical follow up, tat1ing within three months of 85 tr atm nt initiation follow ed by a revi w ev ry three to ix m nth . During each£ 11 w up appointment, pati nt m ay b f£ r d a vari ety f va lid at d ere ning t inquiry of ide effect fr m th ir P P m rd r to identify adver e effect to the appropri ate upp rt and trea tm ent. r imply und rg DT and provide llow up app intment mu t al o includ e a phy ical a e m ent a w 11 a intennittent lab ratory tudi e which w re id entified in detail ba ed on individu al ide effe t f DT. In any vent, pati ent are t be creened for ph y ical, cogniti ve and p ycho logical is ue pri or t initiating trea tm nt and thr ughout the trea tm ent r gim en . A dditi onall y, pati ent and P P' require furth er edu cati n rega rdin g A DT id e effect and th e ir potenti al impact on ov rall health and well -be in g, w hil e P P ' mu t n ure th ey engage in appropri ate knowledg translati on and regu lar cr enin g. Finall y, fu t1her re ea rch i required to fu lly define the adverse effect of ADT in ord er to inco rporate evid ence ba ed reco mm end ati on and develop comprehensive guid elines. 86 Reference Alb rta Pro vincial nit urinary Tum ur Tea m . (2 0 1 ) . fini cal pra tice guide/in : Pro tat ancer. R tri e d fr m http ://www .gu id lin .gov/c nt x t. a px . id=4 7 4 7& arch = pr tat + an r Alibhai . M ., Br u11i , H ., T imil luna, ., J Jm t 11, . Tom lin on, ., T ann ck, I. , . . . Naglie, . (20 10) . Impact f andr g 11-d priva ti 11th rap y n phy ical functi n and quality o f life in m en w ith n onm eta tatic pr tat cancer. Journa l of fin ical On ology, 2 (3 4 ), 5038-5045 . doi: 10.1200/J .20 10.29 . 09 1 A libhai, . M . Yun, L. , Cheung, . M ., & Pa za t, L. (20 12) . creenin g for te 1 oro IS m m en rec iving androge n depri va ti on th rap y. Journal ofth American M edi cal Association, 30 7(3) , 255 -256 . doi: 10. 100 lljam a.20 11.2022 A ll ga r, V . L. , & Nea l, R . D . (2005) . enera l prac titi oners' managem ent of cancer in ngland : econd ary analys i of data fr m the ati onal urvey ofNH pati ents- ancer. E uropean Journal of Cancer Care, 14(5) , 409-41 6. doi: 10.1111 /j . 1365-2354.2005 .00600 Al-S ham si, H ., Lau, A . ., M alik, K ., A lamr i, ., Joa nnidi s, ., orbett, T. , . . . Papaioa nnou, A . (201 2) . The cuiTent practice f creenin g, preventi on, and treatment of androg ndeprivati on-therap y induced o teoporo i in pati ents wi th pro tate cancer. Journal of Oncology, 1-7 . doi: l 0. 11 55/20 12/958596 American Academ y of Fanli1 y Phy ician . (20 15) . Primwy care. Retrieved from http ://www .aafp .org/about/policies/all/primary-care.html American Academy of Ophthalmology. (20 11 ). Catara cts in the adult ~ve. Retri eved from http ://www .guid eline.gov/content. aspx? id =36090# ecti n420 American ancer Society. (20 14 ). Hormone (a ndrogen depriwztion) th erapy fo r prostate can cer. Retrieved from http ://www .cancer.org/cancerlpro tatecancer/detailedguid /prostatecancer-treating-honno ne-therap y American a llege of Rheumato1 gy. (n .d.). Fra cture risk assessment tool. Retri eved from http ://www .rheum ato logy.org/l-Am-A/Rh eum ato logi t/R e earch/Clini cian -R Researchers/Fracture-R i k-A essment-Too l-FRAX Am eri can ro logy A oc ia tion. (n.d.). Erectile c~v.~(un ctio n . Retri eved from http :/ www .auanet .org/education/erectil -dysfun ction .c fm And er on, . J. , regoir , J., Hegele, R . ., outur , P., Manc ini , J., McPherso n, R., ... r, . (20 1 ). 20 I 2 pdate of th e anadian cardiova cul ar oc iety guid elines lor th ' d iagnosi , and treatm nt of dy lipid emia .G r th e preve ntion of cardio as ' ular dis "'a. e in the adult. anadian Journal r~{ ardiolo f!;y, 2 9(2 ), 15 1- 167. de i: 10. 101 6 j .cjca.-0 12. 11 .03 _ 87 andropau e. (2015) . Dictiona!y.com' 21 t .r ferenc .com/br w /andropau e entwy L e icon . Retriev d fr m http ://di tionary Au tralian ancer etwork. (20 10) . lini al pra tice g uidelin e forth mana ment o.f lo cally advanc d and meta tatic pro tate cancer. Retrieved from http ://www .andr logya u tralia rg/wp-c ntent/upload I IN L_ dvanced_Pr tate_ anc r_ uideline .pdf Ba aria ., Muller, D . ., arduc i, M . ., gan, J., & Dob , A. . (2005). Hyperglycemia and in ulin re i tance in m n with pr tat carc in rna wh receive androgen-deprivation therapy. an c r, 106( ), 5 1-58 . d i: 10.1002/cncr.2 1642 Beebe-Dimmer, J., Morgen te111, H . etin, K ., Yee, ., Bart ce , M ., hahinian, Y ., ... chwartz, K . L. (20 11 ). Andr gen depriva ti n therap y and cataract incid enc among elderly pr tat cancer patient in th e nited tate. A nnals a_[ Epidemiology, 21(3) , 156163 . doi : 10.1016/j .annepidem .2010 .10.003 Braga- Ba aria, M . Dob , A . ., Mull er, D . ., arducci, M . ., J hn, M ., gan, J., & Basaria, (2 006) . M etabolic yndrome in men with pro tate ca ncer und ergo ing long- term androgen-deprivation therapy. Journal of Clinical On cology, 24(24 ), 3979-3983. doi : 10.1200/J 0 .2006 .05 .9741 British Columbia ancer Agency. (2 0 12a). B C Can cer Agency Cancer Drug Manual: Goserelin. Retrieved from http ://www .bccancer.bc.ca/NR/rdonl yre /4 8BAAAAD - 17DB-45B3856E-152459A9B28E/58638/go erelin_ monograph_ 1Aug20 12_ form atted.pdf British Columbia Cancer Agency. (2012b) . Drug index: Buserelin . Retrieved from http ://www .bccancer.bc.ca/dru g-databa e- ite/Drug%20 Ind ex/Bu erelin_ m nograph _ 1March2 01 2. pdf British Columbia Cancer Agency. (2012c) . Drug index: Leuprolide. Retrieved fro m http ://www. bccancer. bc.ca/ drug-databa e-site/Dru g%2 0Index/Leuprolide_ monograph _ 1March20 12. pdf Briti h olumbia ancer Agency. (20 13 ). Drug index: D egarelix . Retri eved from http ://www. bccancer.bc.ca/ dru g-database-site/Dru g%2 0Ind ex/Degarelix_ interim _ monograph_ 1August20 13 _ f01matted .pdf British olumbi a ancer Agency. (20 14a). Cancer treatm ent: Radiation Therapy. Retri eved from http ://www. bccancer.bc.ca/PPI/ ancerTrea tment/Radia ti onTherapy/default.htm Briti h o lumbia ancer Agency. (20 14b ). Prostate. Retri ved from http ://www .bccancer.bc.ca/PPIJType ofi ancer/Pro tate/default.htm# trea tmcn t Bruera, ., & Mac Donald , R. N . (1988) . A thenia in pati ents with advanc d ancer. Journal of Pain and y mptom Managern ent. (I) , 9-14. doi : I 0 . 1016/0 85-3924( 8 )90 1 3 ~- 7 Buttaro, . M., rybul ski , J ., Polgar ailey, P., and berg- ook, .1. (20 13 ). Primmy care: .1 collahorate practice (4 th ed. ) . t. Loui , Mi so uri : !sev ier Mosb . By! w, K ., ale, W., Mu tian, K ., tad! r, W . M., Rodin, M ., Il a ll , W ., ... Mobile, . ~ a ll and phys ica l performance defi ciL in oli 'r pati ents with pros tate cancer 1. (- 00 ) 88 underg ing andro gen d priva ti on th rap y. Uro logy, 72(2) 422-427 . doi : 10 .1016/j .urology.200 .03.0 2 anadi an ancer ociety. (n .da) . Anatomy and p hysiology of th e pro tale. Retri ved from http ://www .cancer. ca/en/cancer-inform ation/cancer-type/pr tat /anal m y-a nd -phy iol gy/? regi n=on anadi an anc r ociety. (n.db). Pro tat . p ec~fi an ti n (PSA) test. R tri eved fr m http ://www .cancer. ca/en/canc r-in[i rm ati n/di agn i -and -treatment/te t -and procedure /pro tate- pecific-anti gen-p a/? region=on anadi an ancer ociety. (20 14a) . Prostat can cer: tatistics. Retrieved from http ://www .cancer. ca/en/canc r- in[i rmation/canc r-type/pro tate/ tati ti c /? r gion= bc Canadi an ancer ociety (20 14b ). British olumbia statistics at a glance from ana dia n stati tic . R tri ev d from http ://www .cane r. ca/en/cancer- informati n/cancer10 1/canadi an-cancer- tati tics-publi ca ti on/?region= bc ancer Canadi an Cardi ovascul ar ociety. (n.d.). Framingham risk s ore (FRS). Retrieved from http ://www .cc .cal images/ uid eline /Too l _ and_ alcul ator _ n/Lipi d _ Gui_ 20 12_ FR _ Co l_ EN .pdf#page= l &zoom=auto,- 139,540 Canadi an Nur es ssociation. (20 11 ). N ur e Practition ers. Retrieved fro m http ://www .npnow .ca/ Canadian phthalmological Society. (2007) . Canadian ophthalmological society e1•idencedba ed clinical practice g uidelin e f or th e p eriodic ~ye examination in adults in Canada . Retrieved from C :!Users/virginia/ AppData/Local/Temp/CO VVi ions creeni ngCPG kg_Feb07 .pdf Cappell eri, J. C ., & Ro en, R . C. (2005) . The exual health inventory for m en ( HIM) : a 5-year review of re earch and clini cal experience. Int ern ational J ournal of Imp otence Research, 17(4 ), 307-3 19. Retrieved from http ://www .med cape.com/ viewarticle/50 88 95 _ 1 ary, . K ., Singla, N ., Cowan, J. ., arro ll, P . R ., & Cooperb erg, M . R . (20 14) . Impact of androgen deprivation therapy on mental and emotiona l well -being in m en with prostate cancer: Analysis from the aPSURE registry. The Journal of Urology, 191, 964-970 . doi : 10.10 16/j .juro.201 3. 10.098 herri er, M . M ., Aubin, ., & Higano, . . (2008) . ogniti ve and mood chan g in men und ergoing intennittent combined andro gen blocka ge for non-metastati c pro ' late cancer. Pscyho- neology, 18,237-247 . doi : 10.1002/pon. l401 oll ege of Regi tered Nur e of Briti h olumbia. (20 15a) . cope q('practicefor nurse practition ers: Standards, li111its and conditions. Retri eved from https: prcprodwww .crnb c.ca/ tandards/Li st I tand ardRc ource /6 copcfo r Ps. pd f ' o ll cge o f Rcg ist red Nur c o f Briti h o lumbi a. ( ~ 0 15b ). Applyin[!. the competencies requtred by N urse Practitioners in British ( 'olumbw . Rctri c\ cd from http ://ww w.crnbc.ca/Rcg i trati on/ Li ts//Rcg istrati onRcso urcc. /440 Pl R.pdf 89 urti , K . K ., Adam T . J. , h n ., Pruthi, R . K ., & om t M . K . (200 ). Ana emi a foll wing initiati n of androg n d privati n th erap y for m eta tati c pr tate cancer: a r tro pectiv ch art re i w . Th Aging Mal : Th Official Journal of th Int rn ational Societyforth eStudyof th e A in M al , 11 (4), 15 7- 161. doi : 10.10 0 113 6 55 30 02 1724 Di catol, M ., Pl awny L. , & Di d rich, M . (2 0 10). n m1 a m can er. A nnal. of neology, 21(7) , v iii 167-viii1 72 . d i: 10.1093 /annonc/mdq2 4 f: tathi ou, J . A ., Ba , K ., hip1 y, W . ., H ank , . ., Pil epi ch, M . V ., and1 r, H . M ., & mith, M . R . (2 009) . ardi va cul ar mortality aft er androgen depri vati on th erap y [! r loca ll y advanced pro tate cancer: RTO 5- 1. Journa l of fin ical Oncology, 2 7(1 ), 9299. doi : 10.1200/J .2007.12.3752 koe, J . M ., Punthake , Z. Ran m , T. , Pr btani , A . P., & o ld enb erg, R . (2 0 13 ). lini caJ practice guid elines : cree ning t r type 1 and type 2 di abete . anadian Journal of D iabetes, 3 7, 12- 15. R etri eved from http ://gu idelin es .di abete .calApp _T hem es I D A PG/re ources/cpg_ 20 13_ full _ en.pdf uropean A ociation of Urol gy. (2 0 15) . Guidelin es on prosta te cancer. Retri eved from http ://uroweb.org/wp-co ntent/upl oads/ U-Guid lin e -Pro tate- ancer-20 15-v2 Eziefula, . U ., Grunfeld, E. A ., & Hunter, M . . (20 13 ). 'You know I' ve joined yo ur club .. . I'm the hot flu sh boy' : a qu alitative explorati on of h t flu he and ni ght wea t in m en und ergoing androgen depriva ti on therapy for pros tate cancer. Psycho-Oncology, 22(12), 2823-2830 . doi: 10.1002/pon .3355 Farmacologiaclinica.info. (20 15) . Body image cale. R etri eved fro m http ://too1 .farmacologiacl inica .infolindex .php Gay, H . A ., Mich alski, J . M ., Ham stra, D. A ., Wei , J . T. , Dunn, R . L. , K lein , E . A ., . . . anda , M . G . (20 13). Neoadju vant androgen deprivation therapy lead to imm ediate impainnent of vi tality/honno nal and exual qu ali ty of li fe: Re ults of a m ulticent r pro pective tud y. Uro logy, 82(6), 1363 - 1369 . doi : 10.10 16/j .uro1ogy.20 13.06 .062 Girling, J . ., Whitaker, H . ., Mills, I. G ., & Nea l, D . . (2007) . Pathogene i of pro tate cancer and hormone refractory pro tate can cer. Indian Journal of Urology, ~3 ( I), 35-42. doi : 10.4 103 /0970- 159 1. 3 0265 off, D. ., Lloyd-J nes, D. M ., Bennett, ., oad y, ., ' go tino, R . B., ibbon , R ., . . . Wi l o n, P. (20 14) . 201 3 A /AH guid line on the a e m nt of ca rdio a cul ar risk: report of the Ameri can a ll ege of ardio logy/ meri an Heart oc iati on Ta ' k For 'Con Practi ce uid e1ine . Journal of th e American ollcgc of ardiology, L9( - ), 49- 73 . doi : 10. 1 16110 l. cir.00004 7741.48606 .98 old enb erg, R., Punthakee, Z. (20 1 ). li ni ca l practi ce guid eline.: c finit io n, c lassi fi ' ation and dia gnosis of diabetes, prediab et ', and metaboli c . ndrom e. 'anadian Journal of 90 Diabet , 3 7, 8-11. R triev d from http ://guid line .diab te . a/App _ Them urce /cpg_ 2013 _ full_ n .pdf /r I DA P runfe1d, E . A . Halliday, ., Mmiin P ., Drudge- at , L. (20 12). Andr pau e yndrome in m n treated D r m ta tatic pr tate cancer: a qualitative tudy f th impact f ympt m . anc r ur ing, 35(1) , 63-69 . doi : 10. 1097 .ObOl e3 182 11fa92 Hani ch, L. J. , nera tn , oin, K ., ehrman, P . R ., Vau ghn, . 1., & yne, J. (20 11 ). 1eep and dail y functi ning during androgen deprivation th erapy for pro tate cane r. Europ an Journal of anc r are, 20( 4 ), 549-5 54 . doi : 10. 111 1/j .13652354.20 10.0 1226 .x Harrington, J. M . & Bad g r, T. . (2009). Body image and quality of life in men with prostate cancer. ancer urs ing, 32(2), 1-7 . doi : 10.1097 .Ob01 3e3 18 19 82d 1 Harri , W . P ., Mo ta ghe1, . A ., e1 on, P . ., & Montgo m ery, B . (2009) . Andro gen depri va tio n therapy : progre in und r tanding m chani m of re istance and optimiz ing androgen depletion. ational fini ca l Pra ti e Uro logy, 6(2), 76- 5. doi : 10.1038/ncpurol 1296 Health Force Ontario . (20 13). Nur practitioners. R etri eved from http ://www .hea lthforceo ntario .ca/en/Home ur e /Training_I_Practi ing_ ln_ ntario ursing_ R o1 /Nurse _ Practitioner Heinri h, R . L. , & anz, P . A . (1984). K amof ky performance status rev i ited : re li abi lity va lidity and guidelines. J ournal of Clinica l On cology, 2, 187- 193 . R etri eved from http ://hwmaint.jeo .a copubs.o rg/cgi/content/ab tract/2/3/187 H ervouet, S ., Savard , J. , Iver , H ., & Savard , M . H . (20 13 ). D epression and androgen deprivation therapy for pro tate cancer: A prospective c ntroll ed tudy . H ealth Psychology, 32(6) , 675 -68 4 . doi : 10.103 7 /a0031639 H es -Fischl , A . (20 15) . What is insulin ? R etri eved from http ://www .endocrin eweb.com /conditions/type- 1-di abetes/what-insulin Institute of M edi cine. (2008) . Cancer Care for th e Whole Patient: M eeting Psychosocial f!ealth Needs. National Academic Press. R etri eved fr m http ://www .ncbi .nlm .nih .gov/books /NBK4011 / International Society for exual M edic ine. (20 15). What is anorg asmia and hmt· do es anorgasmia c~f(ect men ? R etri eved from http ://www .i m .info/edu cati n -for-all/ e ual health- qa/what-i -anorgas mia-and -how-doe -a norga mia -a ffect-mcn J ncs, . H . (20 11 ). ardiovascu lar risk during androgen depri va ti o n th eraJ y for pro tate cancer: hould be monitored, and prima ry and ccondary preve ntion o ptimi s d . The British Medical Journal, 342 . doi : 10. 11 36/bmj .d3 105 Karaguzel, ., & Holi ck, M . F. (20 I 0) . iagnos is and trea tm ent of o, teopcnia . RL'\'IL'\\ ' 111 Endocrine and Metabolic Disorders, 11(4), 2 7- 5 1. d i: 10. 1007 s lll 54-010-9154-0 91 Keating, . L. , 'Malley, . J. , & mith M . R . (2006). Diab te and cardi va cular di ea e during androg n d privation th rapy fi r pro tate can r. Journal o.f lini a! On cology, 24(27), 444 -4456 . d i: 10.1200/J .2006.06.2497 Klok M . D ., Jak b d ttir ., & Drent M . L. (2007). The r le f 1 ptin and glu· lin in th regulati n f fi d intak and b dy weight in human : a r vi w . b sity Reviews, 8( 1), 21-34 . doi : 10.111 l/j . l467-7 9X.2006 .00270 . Kroenk , K ., pitzer, R . L. , & W illi am , J. B . (200 1). Validity fa brief depre ion everity m a ure. Journal of Gen ral Internal M di in e. 16(9), 606, 6 1 . doi: 10.1046/j .1525 - 1497.200 1.0 1600 606 .x La pi, F ., Azoulay, L. , iazi, M . T ., Yin, ., Benayoun, ., & ui a, . (20 13 ). A ndr gen d priva tion therapy and ri k of acute kidney injury in patient wi th pr tate cancer. Journal o.f the Am ri an Medica l Asso iation , 31 0(3 ), 289-296. doi: 10.1001 /jama .20 13. 63 Lee, M ., Jim, H . ., F i hm an, M ., Zachariah, B ., Hey ek, R ., Biagiol , M ., & Jacob en, P . B . (2014) . D epres ive ymptomatology in m en receiving an drogen deprivation therapy for pro tate cancer : a controll ed compari on. Psycho-On cology, 24( 4 ), 4 72-4 77 doi : 10.1002/pon .3 608 libido. (20 15). Dictiona ry. com Unabridged. Retri eved from http ://di ctionary.reference.com brow e/libido Locke, J. , & E lliott, S. (2015) . Pro ·tate Can cer-Managing side effects o.f ADT. Retri eved from the British olumbia Cancer Agency website : http ://www .bccancer.bc.ca/NR/rdonl yres I 3 A66FO-D 8BA-4C B6-93C9-64B2AA1453 23/73896/ Prostate ancerpptpd fm anaging id eeffectsofADT. pdf Martel, J. (20 12). Hypogonadism. R etri eved from http ://www .healthline.com/ h alth /hypo gonadism#Overview 1 Mazzola, . R . & Mulhall , J.P . (20 12). Impact of andro gen depri va tion therapy on e ual function . Asian Journal of Andrology. 14(2), 198-203 . doi : 10. 1038/aja .20 11 .106 Mclnto h, H . M ., Neal, R . D ., Ro se, P ., Watson, ., Wilkin n, ., Weller, D ., & ampbell, (2009) . oil ow-up ca re for men with prostate ca ncer and the role of primary care: a ystematic review of international guideline . British Journal of' anccr, J 00, 1 52- 1 60 . doi : 10.1038/sj .bj c.6605080 Mohil e, S. ., Musti an, K., Sylow, K ., ll all , W ., & Dale, W . (2009). Manage ment of co mpli ca ti n f and ro ge n depri vation therapy in the older man . ntical Rc1 ·icH·s 111 On cology/! !enwtologv, 70( ), 235 -2 55 . doi : l 0. 10 16/j .critre one .2 00 .09 .004 Mohil e, . ., acy, M ., Rodin, M., ylow, K., al , W ., Meager, M. R., , tadl 'r, W . M. 92 (20 10). ognitive ffec t of androgen depriva ti on therap y in an older coh rt f m en with pro tate cane r. riti al R evi w in ncology/Hema tolo , 75, 152- 159. d i: 10.1016/j .critrev nc.20 10.06.009 Morgan , A. K ., mith , M . R ., ' Ma ll y, J., & Kea tin g, . L. (20 13). B n den ily t tin g am ong pr tale cancer urvivor trea t d with andr gen-d priva ti on th erap y. ancer, 11 9( 4), 63- 70. doi: 10.1002/ ncr .27 30 M ottet, ., B ellm unt, J., Brier ., van den Bergh, R . ., B lla M ., van a teren , N . J. , ... W iegel, R . T. (20 15) . Guide/in s on pro tate cancer. ur p an ro logy A ociation . R etriev d fro m http ://ur web. rg/wp-content/ up l ad I AU- u id lin e -Pro tate- ancer20 15-v2 .pdf ad l r, M ., A libhai, ., atton, P., atton, , To. , M . J., & Jone , J. M . (20 13) . teop ro i know ledge, health belief , and health y bone behaviour in pati ents on androgen depriva ti on therapy (ADT) fo r pro tate cancer. British Journal of Uro logy, 111 , 130 11309. doi: 10.111 1/j .1464-4 1OX .20 12. 11 777 .x Na nd a, A ., C hen, M., Braccio~ t1e, M . H., Moran, B . J., & D'Am ico, A . V . (2009). Horm ona l therapy use for prostate cancer and mortali ty in men with coronary artery di ea e- induced congestive hea t1 fai lure or myocard ial infarction. Journal of th e American M edical Association, 302(8), 866-873 . doi: 10.10 l/jama .2009. 1 13 7 National Cancer In titu te. (n.d .). NCI dictionary of cancer terms: Neo-adju1 'ant. Retrieved from http ://www .cancer. gov/di ctionary? driD=45800 National Cancer Institute. (20 12). Prostate spec(fic antigen (PSA) te t. Retrieved from http ://www .cancer.gov/type /prostate/p a-fact-sheet National ancer Institute. (20 14) . D epres ion-:for health professionals. Retrieved from http ://www .cancer.gov/about-cancer/coping/feelings/depression-hp-pdq/ National ancer Institute (2015) . Prostate can cer trea tm ent: Treatment option m •eJTieH'. Retrieved from http ://www .cancer.gov/cancertopic /pdq/ treatment/pro late/Patient /page4# _ 172 National omprehen ive ancer Network. (20 15a). NCCN clini ·al practice g uidelines in oncology: Prostate Can cer. Retrieved from http ://www .nccn .org/profes iona l/phy i tan _gl .pdf/pro tate.pdf National ancer omprehen ivc Network. (20 15b). N CN clinical practice g uidelines in oncolo . : Older adult oncology. Retrieved from http ://www .nccn.org/profe. sional / physic ian gl /pdf/ cnior.pdf National an r mprehen ive Network . (20 15c). C /inical prac/1cc g uidclmcs 111 oncology: Sun •i1•orship . Retrieved from http ://www .nccn.org/professiona ls ph stcans gls/ pdf/, urviv rship .pdf 93 ation al ompr h n ive ancer etw rk. (2 0 15d). lin i al practice uidelin in oncology: i tr mana m nt. Retrieved from http ://www .nccn . rg/profe ional I /phy ician_ gl /pd f/di tre .pdf Na ti onal In titute of H alth . (200 1). a tiona ! hoi t ro l Educa tion Pro ram : ATP JJJ uid line A t-A-Glance. Retri eved fro m http ://www .nhlbi .nih.g v/fil e /doc /guid eline /atglance.pd f ati onal In titu te f Health. (20 12). Principle of M edlin e subj ct h adings. Retriev d from http ://www. nlm .nih .g v/b d/di ted/ me htutorial/princ iple ofm edline ubj ectindexing /principl e /02 .html National In titu te for Hea lth and are peri ence ( I ). (20 14) . Pros tate cane r: D iag nosis and treatment. Retrieved from http ://www .nice. rg.uk/guid ance/ 175 euberger . B . (2003) . Mea ure of fa tigue: T he Fati gue Q uestionnaire, Fa ti gue eve1ity cale, Multidimen ional As es ment of Fati gue cale, and h rt Form -36 V itality (Energy/Fatigue) ub cale of the hort Fonn Health urvey . Arth ritis are and R e earch, 49(S5), 175- 1 3. doi : 10.1002/art.ll 405 Ni hiyama, T. , Kanazawa, S., Watana be, R ., Terunu ma, M. , & Takaha hi , K . (2004) . Influ ence of hot fla he on qu ali ty of life in pati ents w ith pro tate cancer treated with andr gen deprivation therapy. l nt rnationa l Journa l o_[Urology, 11,735-74 1. doi : 10. 1111 /j .l 4422042 .2004.00896 Oliffe, J. (2006). Em bodi ed masculinity and androgen depriva tion th erapy. Sociology o.f H ealth & Illn ess, 28( 4), 4 10-432. doi: 10. 11 11/j .1467-9566 .2006.00499 Oncology Pro. (2008) . P e1jorma nce Scales: Karnof. ky & ECOG s·core. Retrieved from http ://oncologypro.esmo.org/ uid elines-Practice/Practice-Tool /Perfonnance- cal Pagana, K. D ., & Pagana, T. J. (20 13). Bl ood stu dies . In . Pike-MacDonald (Ed .), !lfosby 's Canadian manua l o.f diagnostic and laborat01y tests (pp . 30 1-555). Toronto, : Mo by. Papaioannou , A ., Morin, S., heung, A . M ., Atkin on, ., Brown, J. P ., Feldman, ., ... Le li e, W . D . (20 I 0). 20 10 clinical practice guideline for the dia gno i and managem ent of o teoporosi in anada. Canadian M edical Association Journal, 1R2( 17) , l 64-1 73. doi : 10.1503/cmaj. l 00771 Perlmutter, M . A ., & Lepor, H. (2007) . ndrogen depri ation therapy in th treatment of advanced prostate cancer. Re1•iews in Urolo ry, 9( 1), . Retrieved from http : //www .ncbi .nlm .nih/g vpmc/articles/PM 18 15 9 ode, M . J ., & mith , M. R. ( 002). 1 res ton 111 men rccct\ mg Pirl , W . ., iegel, J. 1. , androgen d privation therapy for prostate an r: a pilot stud y. p,ycJw-Oncology. I 1( 6 ), 518-52 . doi : I 0. 1002/pon.592 94 Pro tate ancer Foundation. (n.d .). About th pro tate. Retri v d fr m http ://www .pcf.org/ it /c.leJRlR r pH/b .5 02023 /k.B322/ bout_ th _Pro tate.htm Pro tate anc r Foundati n. (2014). Pro tat an r FAQ . Retri ved from http ://www.p f.org/ it /c.l JRIR r pH/b .5 00 5 llk.645 Pro tat anc r FA .htm P ychometrician (20 15). In M rriam Wt b. I r. R etri eved from http ://www .m erriam web ter. cornJdicti nary/p ych m tri ian gua zz tti , ., Porpiglia, ., Ru , L. , ... 0 ta c li , L. (20 13). aini, A., B rruti , ., ra cco, P ych logica l di tre in men with pr tate cane r receiving adjuvant androgendepriva tion th erap y. Uro logic On cology, 31,3 52-358 . doi : 10.1016/j .ur lonc .2011 .02.005 aylor, P . J. , K eating, . L. , & mith, M . R . (2009) . Pro tate cancer urvi vor hip : Prev ntion and treatment of the adver e effect of andro gen deprivati n th erapy. Journa l of en era! Internal M edicin e, 24(2), 3 9-394 . doi : I 0. 1007 I 11606-009-0968-y aylor, P . J. , & mith, M . R . (2013) . Metabolic co mpli cations of androgen deprivation therapy for pro tate cancer. Th e Journal of Uro logy, 189, 34- 44 . doi : 10.10 16/j .juro .20 12 .11 .017 il verbery, C. (2 0 15). Imp otence. About Relationships. Retrieved from http :// exuality.about .cornJod/Erectile-D ysfunction/a!Impotence.htm Soyupek, F., oyupek, ., Perk, H ., & Ozorak, A. (2008) . Androgen depriva ti on therap y for pro tate cancer: ffect on hand fun ction. Uro logic, 26, 141-146. doi: 10.10 16/j .uro1onc.2006. 12 .0 14 Stevens, L. M. (2006) . Medical jomnal . Th e Journal of th e American M edica l Association , 295(15) , 1860. doi : 10.100 1/jama .295. 15 .1860. Stull, V . B ., Snyder, D . ., & Demark-Wahnefried , W . (2007) . Life tyle interventions in cancer survivors: D e igning pr grams that meet th e need of thi vulnerabl e and growing population. The Journal of Nutrition, 13 7, 243 -248 . R etrieved from http ://jn.nutrition.org/content/13 7I l /243 .full Tadros, N . N ., & Garzotto, M . (20 1 1). Androgen deprivation therapy for pro tate cancer: simple . Asian Journal ofAndrology. 13(2) , 187- 188 . doi : 10. 1038/aja .2 0 10.174 ot so T e to terone. (20 15). In . .ford Eng lish Dictionwy Retri e ed from http ://www .ocd .com/ view/ ntry/199759? rcdircctcd rom te to tcron c#eid The BMJ . (20 15). finica l r e1•i e ii 'S. Rctri cv d from http ://www .bmj .com/about-bmj resources-a authors/a1ii clc-typ e /c l i nica l-rcvi cw 95 T rna n , J. R ., haudhary, R ., Br uwer M . . (20 15). f[i ti ene f guideline di minati nand implem ntati n trat g ie n h alth care pr G i nal ' b havi ur and pati nt outcome in th cane r car c ntext: a y temati review pr t c 1. y I mali R vi w, 4(113) . d i: 10. 11 6/ 1364 -0 15-0 100-9 Triacylglycerol. (20 15). In Di tionGly. om. R tri r w e/tri acylglycer 1 d fr m http ://di c tionary.r [! rence.c m ai, H. K., D 'A mico, . V ., ad t k , ., hen, M ., arr II , P. R. (2007). Andr ge n depri ati n th rap y [! r 1 calized pro tate cancer and the ri k f cardiova c ular m rtality. Journal of th aliona l anc r lnstilut '. 99(20) 15 16- 1524. doi : 10.1093 /jnci/djm 168 T ai, H . T. , K eatin g, . L., Van D en e I n . K ., Haque, R ., a id y- Bu hrow , . ., Y d, M . ., ... Po to ky, . L. (20 15 ). Ri k f diabete among patient recei ing prim ary androgen depri ati n th rapy [! r clini ca ll y loca li zed pr tate ca ne r. The Journal of Urology 193(6) , 1956- 1962. d i: 10. 10 16/j .j ur .2014 . 12.027 U. F od and Dru g ociation. (20 13 ). nRI-1 a onists: Lahel change-In creased risk of diabetes and cardiova cu lar disease ( pdate) . Re tri eved from http ://pr xy. library. unbc .ca:2642/ afety/MedW atch/ afetylnfo nn ati on/ afetyA iert forHumanM edicalProdu ct /ucm230359. htm U. Preventative ervice Ta k Force. (20 14 ). ognitiPe irnpairment in older adults: Screening . Retrieved fro m http ://www .u preventativ erv icesta kforce .org/Page/Document /Recommendatio n tatementFinal/cognitive- impairmen t-in-o ld er-ad ult - creening van Andel, ., & Kurth, K . H . (2003). The impac t of androgen deprivation therapy n hea lth related quality of life in asymp tomatic men with lymph n de po iti ve pro tate ca ncer. European Uro logy, 44, 209-214. doi: 10. 1016/ 0302-2 (03 )00208-2 van Londen, G. J ., Levy, M . ., P erera, ., el on, J. B ., reen pan, . L. (200 ). Body composition changes during andro gen depri va tion therap y for pro tate ca n er: 2-year prospective stud y. fini cal R e1•ie11.· in Oncology/Hematology. 6 , 172- 177. doi : 10. 10 16/j .critrevonc .2 008.06 .006 Venkateswaran, ., Marge!, D ., Yap, ., Her ey, K ., Yip, P ., & le hn er, . E . (20 12). mpari on of erum tes tostero ne level in pro tate cancer pati ent r i ing LHRH agoni t therap y with or w ithout the remova l f the pro tate. anadian Urolo?;v Association Journal, 6(3 ), 183 - 186 . doi : 10.5489/cuaj . 11 27 V dermai e r, A., Linden, W ., & iu , . (2009) . c r enin g Ii r emotional di trcs 111 cancer pati ent : A ystemati c rev iew of a sessm nt in trum ent . Journal o(tlu.: atwnal Cancer Ins titute, 101( 2 1) , 1464- 14 8. doi : 10. 109 /jnci/djp 3 6 Watter , W . . (20 15) . De finin g evidence- t ased c lini ca l prac ti ce guid eline .. . lmencan A ·ode my ol rtlwpacclic urgcons, 9(3 ). Retri c ed from http : WW\\' .aaos.org ne\\ s /aaosnow/jul08/rescarch2 .asp 96 Wilkin on, . . Brundage, M . . & iem n , R. (200 ). ppr ach to primary care foll w-up f patient with pr tate ca ncer. anadian Fa mily Phy si ian , 54(2 ), 204-2 10. R etri eved fr m http ://www .ncbi .nlm .nih.g v/pmc/article /PM 22783 12/ ne Di ea e. (n.d.) FRAX: W orld Health rgani zati n ollab rating ntr [! r M etab lie WI-!0 Fra tur Ri k A m nt Too l. Retriev d from http ://ww w. hef.a c.uk /FRAX/ind x.a p W orld Health rganiza ti n. (1 9 7) . WH Q L U asurin quality of l{fe. R triev d from http ://www .who.int/m ental_healthlm dia/6 .pdf Yu, E. Y ., Kuo, K . F., ul ati , R., hen, ., ambol, T. ., Hall , . P., .. . Higan , . . (201 2) . Long- t nn dynami c of bone mineral den ity during intermitt nt andro gen depriva tion fo r men with nonm ta tatic, h nnon - n itive pro tate cancer. Journal of Clin ical On cology, 30( 15), 1 64-1 70. doi: 10. 1200/ J .20 11 .3 .3 745 97 Appendix A Pharmacolo gical ADT Medication Luteinizing hormone relea ing honn ne agoni t • Leuprolide • Goserelin • Bu erelin GnRH antagonists • D egarelix Anti-androgens • Flutamide • BicaJutamide • Ni lutamide Mechani m f A ction The e m dications timulate the rel ea e of lut inizing hom1one cau sing an initial 1 vation in erum androgen . Chronic admini trati n causes a reduction in the secretion of luteinizing hormone and androgens through down regulation of LHRH receptors. Competitively binds to the GnRH receptors in the pituitary, which reduces the release of follicle stimulating honnone and luteinizing honnone which reduces the release of testosterone. Binds to androgen receptors, inhibiting the binding of testosterone and dihydrate to terone. Indicati n Indicated for localized, locally advanced di a e, bi chemically recurrent disease (increasing P A) and m etastatic prostate cancer Used in m etastatic prostate cancer, as an alten1a ti ve to GnRH agonists . Can be used as first lin mono therapy for advanced prostat can er, in combination with GnRH agonist for advan ed prostate cancer Ad1nini tration and Dosage Leuprolide: 1 month d pot 7.5 mg IM, 3 month depot 22.5 mg IM or 4 month depot 30 mg IMOR 3 month depot 22.5 m g SC or 6 month depot 45 m g Goserelin : 3.6 m g SC monthly or 10.8 mg SC ev ry 3 months. Busere1in: 6.3 m g SC every 8 weeks or 9.45 m g C every 12 weeks . Two 120 m g injections (2 40 m g total) SC on da y 1 followed by 80 mg SC monthly. Flutamide : 250 mg PO thre time daily Bicalutamide: 50 mg PO once daily ilutamidc: 00 mg P once dail for 30 days or less, 98 or a econd lin th erapy after pr gre 1 n n nRH agoni t YP17 inhibit r • Ketoconazo l • Abirateron (B A , 20 12a; B then 150 mg P daily. Ketocona zo le in th e adrenal gland re ult in a redu cti n in the produ ction of andro gen . A , 20 12b; B A , 20 12c; B Abiraterone: 1 gram once daily P pr tate cancer after chem therapy trea tment failure . A , 20 13; Perlmutter & Lcpor, 2007) . 99 ppendix B arch Fl w Literatur Potentially relevant paper identifie d by ha1i Addit ional records identified through database searching (n =1198) other sources (grey literature, hand searching) (n =140) lr Paper for review (after duplicates removed) (n =1338) M c: c: Q) Q) 1... u V) Titles screened Records excluded after (n =1338) review of title/abstract (n =1288) > ."!:: LU Full -text articles asses se d for Full-text articles excluded, eligibility with reasons (n =SO) ~ (n =2 8) + -Main reason for exclusion Additional articles selected recommendations from references of full text articles (n =3 ), but ultimately excluded due to exclusion criteria Total papers mcluded in the review (n =22 ) wa s lack of screening