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Polycystic ovary syndrome in adults : a literature review and clinical practice guideline for the primary… Meidinger, Lindsey 2016

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Running head: POLYCYSTIC OVARY SYNDROME IN ADULTS                                            1 			 POLYCYSTIC	OVARY	SYNDROME	IN	ADULTS:	A	LITERATURE	REVIEW	AND	CLINICAL	PRACTICE	GUIDELINE	FOR	THE	PRIMARY	CARE	NURSE	PRACTITIONER				By	Lindsey	Meidinger	RN,	BScN,	MN-NP	Family	(C)						 CULMINATING	PROJECT	SUBMITTED	IN	PARTIAL	FULFULLMENT	OF	THE	REQUIREMENTS	FOR	THE	DEGREE	OF		MASTER	OF	NURSING	–	NURSE	PRACTITIONER	In	THE	FACULTY	OF	GRADUATE	AND	POST	DOCTORAL	STUDIES	School	of	Nursing	THE	UNIVERSITY	OF	BRITISH	COLUMBIA	©	Lindsey	Meidinger	 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  2 Table	of	Contents	Table	of	Contents	..................................................................................................................................	2	Abstract	...................................................................................................................................................	4	Introduction	...........................................................................................................................................	5	Current	Guidelines	...............................................................................................................................	6	Gaps	.....................................................................................................................................................................	7	Purpose	....................................................................................................................................................	7	Methods	...................................................................................................................................................	8	Pathophysiology	...................................................................................................................................	9	Diagnosing	PCOS	.................................................................................................................................	10	Phenotypes	.....................................................................................................................................................	11	Diagnosis	.........................................................................................................................................................	12	Diagnostic	criteria.	.......................................................................................................................................................	13	Diagnostic	controversy.	.............................................................................................................................................	15	PCOS	and	Insulin	Resistance	..........................................................................................................	16	What	is	Insulin	and	Insulin	Resistance?	...............................................................................................	16	Insulin	Resistance	and	PCOS	.....................................................................................................................	16	Recommendations	........................................................................................................................................	18	Management	Guidelines	.............................................................................................................................	18	PCOS	and	Cardiovascular	Disease	................................................................................................	19	Recommendations	........................................................................................................................................	21	Management	Guidelines	.............................................................................................................................	21	PCOS	and	Cancer	Risk	.......................................................................................................................	22	Recommendation	..........................................................................................................................................	24	Management	Guidelines	.............................................................................................................................	25	PCOS	and	Obesity	...............................................................................................................................	25	Recommendations	........................................................................................................................................	26	Management	Guidelines	.............................................................................................................................	27	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  3 PCOS	and	Mental	Health	...................................................................................................................	28	Recommendations	........................................................................................................................................	30	Management	Guidelines	.............................................................................................................................	31	PCOS	and	Infertility	...........................................................................................................................	32	Recommendations	........................................................................................................................................	34	Management	Guidelines	.............................................................................................................................	34	PCOS	and	Dermatology	.....................................................................................................................	35	Recommendations	........................................................................................................................................	36	Management	Guidelines	.............................................................................................................................	37	Diagnostic	workup	.............................................................................................................................	38	Other	Conditions	to	Rule	In	or	Rule	Out	...............................................................................................	38	Nurse	Practitioners	...........................................................................................................................	41	Scope	of	Practice	...........................................................................................................................................	41	What	is	a	Guideline?	..........................................................................................................................	42	PCOS	Guideline	..............................................................................................................................................	43	Discussion	.............................................................................................................................................	43	Implications	for	Practice	............................................................................................................................	44	Further	Research	and	Projects	................................................................................................................	45	Conclusion	............................................................................................................................................	45	References	............................................................................................................................................	47	Appendix	A	...........................................................................................................................................	58	Appendix	B	...........................................................................................................................................	60	Appendix	C	............................................................................................................................................	61		 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  4 Abstract	Polycystic	ovary	syndrome	(PCOS)	is	a	complex,	multifaceted	syndrome	with	multiple	health	implications	and	long-term	health	risks	(Fauser	et	al.,	2012).	Women	with	PCOS	require	management	and	guidance	from	their	primary	care	NP	in	collaboration	with	multiple	specialists.	The	heterogeneity	of	the	syndrome	makes	diagnosis,	symptomatic	treatment,	and	long-term	management	complex	and	individualized	(Fauser	et	al.,	2012).		Long-term	complications	of	PCOS	include	increased	risk	for	insulin	resistance	(IR),	cardiovascular	disease	(CVD),	endometrial	cancer,	obesity,	depression	and	anxiety,	infertility,	and	various	dermatological	manifestations	(Fauser	et	al.,	2012).	Nurse	Practitioners	(NP)	are	in	a	unique	position,	as	primary	care	providers,	to	co-manage	these	women	with	various	specialists.	Currently	in	Canada,	however,	there	are	no	primary	care	guidelines	for	the	diagnosis	and	management	of	PCOS.	This	literature	review	was	developed	for	the	purpose	of	finding	supporting	evidence	for	the	creation	of	a	clinical	practice	guideline	to	assist	NPs	in	the	diagnosis	and	long-term	management	of	adult	women	with	PCOS.			Keywords:	Polycystic	ovary	syndrome,	cardiovascular	risk,	insulin	resistance,	nurse	practitioner,	guideline,	primary	care		 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  5 Introduction	Polycystic	ovary	syndrome	(PCOS)	is	a	multifaceted	disease	with	a	wide	range	of	clinical	presentations,	varying	diagnostic	criteria,	and	multiple	long-term	metabolic	and	cardiovascular	complications	(Fauser	et	al.,	2012).	The	complexity	of	symptoms	and	complications	of	PCOS	require	involvement	of	various	different	specialists;	however,	the	primary	care	provider,	such	as	a	Nurse	Practitioner	(NP)	or	General	Practitioner	(GP),	is	involved	in	the	overall	long-term	co-management.		 With	an	advanced	scope	of	practice,	NPs	are	in	a	unique	position	to	initiate	investigations	and	rule	out	other	possible	causes	of	the	presenting	complaint	thereby	preventing	unnecessary	specialist	referrals	and	cost	to	the	health	care	system.	NPs	are	also	involved	in	long-term	management	of	patients	with	PCOS	when	initiating	screening	to	prevent	chronic	complications	of	the	disease.	Complications	include	increased	risk	of	insulin	resistance	(IR),	cardiovascular	disease	(CVD),	endometrial	cancer,	obesity,	depression	and	anxiety,	infertility,	and	various	dermatological	manifestations	(Legro	et	al.,	2013).		 Currently,	in	Canada,	there	are	no	primary	care	guidelines	for	the	diagnosis	and	management	of	PCOS.	Primary	care	providers	have	limited	guidance	regarding	initial	testing	and	long-term	screening	precautions,	thus	contributing	to	under	or	over	ordering	of	diagnostic	tests,	increased	cost	to	the	healthcare	system,	and	potential	missed	opportunities	for	early	screening	and	prevention.	This	literature	review	will	provide	the	evidence	necessary	to	create	a	clinical	practice	guideline	for	use	by	NPs	in	primary	care	with	the	purpose	of	guiding	clinical	practice	and	removing	uncertainty	regarding	initial	diagnostic	procedures,	referrals,	and	long-term	management	for	adult	women	with	PCOS.		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  6 Current	Guidelines		 Five	specific	noteworthy	guidelines	were	reviewed	and	frequently	referenced	for	purposes	of	this	paper.	One	of	these	is	the	Australian	document	from	2015	entitled	Evidenced-based	Guideline	for	the	Assessment	and	Management	of	Polycystic	Ovary	Syndrome	by	the	Jean	Hailes	for	Women’s	Health	organization	in	collaboration	with	the	Centre	for	Research	Excellence	in	Polycystic	Ovary	Syndrome	(Jean	Hailes	for	Women’s	Health,	2015).	This	particular	guideline	provides	an	in-depth	evidence	based	guide	to	the	care	of	women	with	PCOS	based	on	various	aspects	of	the	syndrome.	Advice	from	this	document	can	be	very	helpful	in	guiding	care,	but	is	not	very	concise	or	easily	accessible	for	a	quick	reference	by	the	primary	care	NP.	The	Jean	Hailes	for	Women’s	Health	organization	also	created	a	tool	entitled:	Polycystic	Ovary	Syndrome	GP	Tool.	This	provides	a	quick	reference	for	GPs	regarding	the	initial	workup	and	management	of	a	woman	presenting	with	PCOS.	This	tool	is	easily	accessible	and	straightforward	to	use,	however	it	is	targeted	towards	GPs	in	Australia	(Jean	Hailes	for	Women’s	Health,	2015a).	The	Endocrine	Society	also	has	developed	guidelines	entitled:	Diagnosis	and	Treatment	of	Polycystic	Ovary	Syndrome:	An	Endocrine	Society	Clinical	Practice	Guideline	(Legro	et	al.	2013).	This	guideline	is	also	a	very	extensive,	comprehensive	guideline	that	examines	the	most	important	aspects	for	diagnosis	and	management	of	PCOS.	This	guideline,	similar	to	the	Jean	Hailes	for	Women’s	Health	guideline,	is	thorough,	but	neither	succinct	nor	targeted	for	use	in	the	primary	care	setting.	Also	of	note,	three	different	consensus	workshops	have	been	held	in	Europe	with	members	from	the	European	Society	for	Human	Reproduction	and	Embryology	(ESHRE)	and	the	American	Society	for	Reproductive	Medicine	(ASRM)	to	establish	guidelines	for	the	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  7 diagnosis	and	management	of	PCOS.	The	first	of	these	workshops	took	place	in	Rotterdam,	the	Netherlands	in	2003,	and	resulted	in	the	creation	of	the	most	widely	accepted	diagnostic	criteria	to	date:	the	Rotterdam	Criteria	for	Diagnosis	of	PCOS	(Rotterdam,	2004).	The	second	took	place	in	Thessaloniki,	Greece	in	2007	and	focused	on	infertility	treatments.	This	resulted	in	the	document	entitled:	Consensus	on	Infertility	Treatment	Related	to	Polycystic	Ovary	Syndrome	(Tarlatzis,	2008).	The	third	workshop	took	place	in	Amsterdam,	the	Netherlands,	in	2010	and	resulted	in	the	document	entitled:	Consensus	on	Women’s	Health	Aspects	of	Polycystic	Ovary	Syndrome	(PCOS):	the	Amsterdam	ESHRE/ASRM-Sponsored	3rd	PCOS	Consensus	Workshop	Group	(Fauser	et	al.,	2012).	This	most	recent	document	summarizes	the	current	knowledge	regarding	polycystic	ovary	syndrome.		Gaps		 All	five	of	these	documents	are	highly	cited	and	reputable	evidence-based	guidelines	developed	by	experts	in	each	of	their	respective	fields.	However,	they	are	either	very	in-depth	and	lack	tangible,	easy	to	obtain	information	or	are	not	targeted	for	direct	patient	care	by	the	NP	in	BC.	Nurse	Practitioners	in	BC	would	benefit	from	a	framework	for	making	evidenced-based	clinical	decisions	that	is	clear,	succinct,	and	summarizes	the	current	guideline	recommendations.	Purpose	This	literature	review	seeks	to	understand	the	current	accepted	diagnostic	criteria,	the	controversies	in	diagnosis,	and	the	gaps	that	exist	in	clinical	practice	knowledge.	It	will	investigate	potential	complications	of	PCOS	and	evaluate	the	recommendations	made	in	the	recent	meta-analyses,	systematic	reviews,	and	current	guidelines	regarding	diagnosis,	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  8 workup	and	screening.	It	will	focus	on	the	NP	scope	of	practice	in	BC	and	take	into	consideration	limitations	regarding	making	diagnoses	and	ordering	tests.	Evaluating	these	aspects	of	the	diagnosis	and	management	of	PCOS	will	assist	in	the	development	of	a	tool	to	assist	NPs	in	the	care	of	adult	women	with	PCOS.		In	Canada,	there	is	currently	no	guideline	or	decision-making	tool	for	the	diagnosis	or	management	of	PCOS	in	the	primary	care	setting.	This	contributes	to	delayed	diagnosis	due	to	uncertainty	regarding	initial	diagnostic	tests	and	referrals,	insufficient	supports	for	lifestyle	changes,	and	inadequate	follow	up	and	long-term	management	for	the	various	complications	associated	with	PCOS.	Also,	there	is	a	potential	for	increased	burden	on	the	health	care	system	due	to	either	over	ordering	of	diagnostics	or	under	screening	for	the	long-term	complications	associated	with	PCOS.	A	guideline	would	outline	initial	diagnostics,	other	conditions	that	need	to	be	considered	and	ruled	out,	and	the	long-term	screening	necessary	for	women	with	PCOS	throughout	their	life.			Methods		 In	preparation	for	this	literature	review	and	creation	of	the	clinical	practice	guideline,	multiple	databases	were	accessed	and	various	search	terms	were	used.	Limits	were	set	to	include	only	articles	published	in	the	past	10	years,	humans,	and	review	articles.	The	reference	pages	of	articles	were	also	analyzed	in	order	to	obtain	more	information	about	specific	journal	articles	or	studies	that	were	commonly	sited.	Databases	searched	include	the	UBC	Library	search,	Pubmed,	Medline,	and	The	Cochrane	Database.	Search	terms	included	a	combination	of	polycystic	ovar*	syndrome	AND	cardiovascular	disease;	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  9 cardiovascular	disease	risk;	insulin	resistance;	metabolic	abnormalities;	obesity;	endometrial	cancer;	cancer;	infertility;	depression;	mental	health.		 Searches	for	current	practice	guidelines	were	performed	via	Google	search	engine	with	terms	including	polycystic	ovary	syndrome	and	polycystic	ovary	syndrome	guidelines.	Site-specific	searches	were	also	performed	on	the	Society	of	Obstetricians	and	Gynaecologists	of	Canada	(SOGC)	website	and	the	American	Congress	of	Obstetricians	and	Gynecologists	(ACOG).		Pathophysiology		 The	pathophysiology	of	PCOS	is	complex	and	multifactorial	and,	even	after	much	investigation	into	the	pathogenesis,	the	cause	remains	relatively	unclear.	In	addition	to	the	numerous	genes	that	are	identified	with	PCOS,	there	is	growing	evidence	to	suggest	that	particular	environmental	factors	such	as	low	socio-economic	status,	smoking,	poor	diet,	and	lack	of	exercise	also	contribute	to	the	development	of	the	syndrome	(Barthelmess	&	Naz,	2015).	Additionally,	hypotheses	exist	suggesting	high	testosterone	levels	in-utero	seem	to	contribute	to	the	development	of	the	disease	later	in	life	(Vito,	2006).		Although	the	exact	cause	is	still	largely	unknown,	central	to	this	syndrome	is	the	hormone	imbalance	created	by	elevated	androgen	and	insulin	levels	(Teede,	Deeks,	&	Moran,	2010).		The	complex	interplay	of	genetic,	environmental,	and	hormonal	factors,	contribute	to	the	development	of	PCOS	and	directly	correlate	to	an	increase	in	metabolic	complications,	cardiovascular	risk,	endometrial	cancer,	obesity,	depression,	infertility,	and	various	dermatological	manifestations	(Huang	&	Coviello,	2012).	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  10 Diagnosing	PCOS	Polycystic	ovary	syndrome	(PCOS)	is	one	of	the	most	prevalent	endocrine	disorders	in	women,	affecting	as	many	as	15%	of	females	(Fauser	et	al.,	2012).	It	is	usually	detected	during	the	early	reproductive	years	due	to	presenting	complaints	such	as	menstrual	irregularity,	clinical	hyperandrogenism,	or	infertility	(Fauser	et	al.,	2012).	The	clinical	presentation	varies	according	to	severity	of	the	illness	and	the	diagnostic	criteria	used.	Three	different	criteria	have	been	proposed	and	are	outlined	in	Table	1.	In	1990,	the	first	diagnostic	criteria	were	developed	by	the	National	Institutes	of	Health	(Lujan,	Chizen,	&	Pierson,	2008).	These	criteria	required	the	presence	of	both	menstrual	disturbances	(either	oligovulation	or	anovulation)	and	clinical	or	biochemical	signs	of	hyperandrogenism	(Lujan	et	al.,	2008).	Since	this	time,	research	has	shown	that	PCOS	encompasses	a	much	more	varied	clinical	presentation,	which	led	to	the	development	of	the	Rotterdam	criteria	in	2003.	These	criteria	encompass	a	broader	expression	of	the	syndrome	and	require	two	of	the	following	three	criteria:	oligo-	and/or	anovulation,	clinical	and/or	biochemical	hyperandrogenism,	or	polycystic	ovaries	(Rotterdam,	2004).	Initially	experts	had	difficulty	with	the	Rotterdam	criteria,	because	these	broader	diagnostic	criteria	made	it	possible	to	diagnose	PCOS	in	the	absence	of	menstrual	irregularity	or	hyperandrogenism	–	two	components	that	were	previously	thought	to	be	requirements	of	the	syndrome	(Lujan	et	al.,	2008).	In	2006,	The	Androgen	Excess	and	Polycystic	Ovary	Syndrome	Society	proposed	a	revised	set	of	criteria	that	recognized	the	broad	clinical	presentation	of	PCOS	but	required	the	presence	of	both	hyperandrogenism	and	ovarian	dysfunction;	the	latter	being	defined	by	oligo-	and/or	anovulation	and/or	polycystic	ovaries	(Lujan	et	al.,	2008).	However	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  11 currently,	the	most	widely	accepted	diagnostic	criteria	still	remain	the	Rotterdam	criteria	due	to	its	broad	and	inclusive	nature	(Legro	et	al.,	2013).			Table	1	 		 		Comparison	of	the	diagnostic	criteria	for	Polycystic	Ovary	Syndrome	(PCOS)	National	Institute	of	Health	(NIH)	1990	Rotterdam	2003	 Androgen	Excess	and	Polycystic	ovary	syndrome	(AE-PCOS)	Society	2006	Both	needed	for	diagnosis:	 Two	of	three	needed	for	diagnosis:	 Both	needed	for	diagnosis:	1.	Oligo-ovulation	or	chronic	anovulation	1.	Oligo-ovulation	or	chronic	anovulation	1.	Ovarian	dysfunction	(oligo/anovulation	and/or	polycystic	ovarian	morphology)	2.	Clinical	and/or	biochemical	signs	of	hyperandrogenism		2.	Clinical	and/or	biochemical	signs	of	hyperandrogenism			2.	Clinical	and/or	biochemical	signs	of	hyperandrogenism			 3.	Polycystic	ovaries	 		*	note:	all	three	diagnostic	criteria	require	exclusion	of	other	etiologies	of	androgen	excess	and	anovulatory	infertility	prior	to	diagnosis	of	PCOS	Adapted	from	Lujan,	Chizen,	and	Pierson	(2008)			Phenotypes	Due	to	the	expansion	of	the	diagnostic	conditions	within	the	Rotterdam	criteria,	four	different	subgroups,	or	phenotypes,	have	been	recognized	based	on	their	clinical	presentation	(Table	2).	The	breakdown	of	the	four	different	phenotypes,	A,	B,	C,	and	D,	is	based	on	presence	or	absence	of	oligo-	or	amenorrhea,	clinical	and/or	biochemical	signs	of	hyperandrogenism,	and	polycystic	ovarian	morphology.	The	most	prevalent	and	also	most	associated	with	long-term	health	risks,	is	phenotype	A,	which	includes	all	three	clinical	characteristics	(Rotterdam,	2004).			 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  12 Table	2	 		 		 		 		Phenotype	classification	based	on	Rotterdam	(2003)	diagnostic	criteria	for	PCOS			 Phenotype	Characteristic	 A	 B	 C	 D	Oligo-anovulation	 +	 +	 -	 +	Hyperandrogenemia	 +	 +	 +	 -	Polycystic	morphology	 +	 -	 +	 +		Diagnosis		 Although	it	is	not	within	the	NP	scope	in	BC	to	diagnose	PCOS	independently	(College	of	Registered	Nurses	of	British	Columbia,	2015),	NPs	must	be	aware	of	the	diagnostic	criteria	when	ordering	tests	and	hypothesizing	on	potential	differential	diagnoses.	The	heterogeneity	of	the	signs	and	symptoms	of	PCOS	make	the	syndrome	difficult	to	diagnose;	however,	with	appropriate	resources,	NPs	can	be	well	educated	regarding	the	diagnostic	criteria	for	PCOS	and	other	disorders	that	can	present	with	similar	symptoms,	resulting	in	appropriate	use	of	diagnostic	tests	and	prompt	referrals.	Understanding	the	definition	of	the	term	syndrome	will	help	explain	how	the	heterogeneity	of	the	clinical	presentation	of	PCOS	contributes	to	the	complexity	of	diagnosis.	According	to	Azziz,	et	al.,	a	syndrome	is,	“a	collection	of	signs	and	features,	in	which	no	single	test	is	diagnostic.	In	essence,	the	whole	(or	global	assessment)	is	greater	than	the	sum	of	the	individual	features”	(Azziz	et	al.,	2009,	p.	4237).	This	definition	fits	well	with	PCOS	as	the	heterogeneity	of	the	syndrome	is	broad	with	varied	clinical	presentations,	and	there	is	no	single	diagnostic	test	to	detect	the	presence	of	PCOS.	Along	with	the	clinical	features	and	manifestations	required	for	diagnosis	of	PCOS,	the	syndrome	is	associated	with	a	number	of	additional	signs	and	symptoms,	which	will	be	explored	within	the	context	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  13 of	this	paper.		Diagnostic	criteria.		 One	of	the	three	diagnostic	features	of	PCOS,	according	to	the	Rotterdam	criteria,	is	irregular	menses	(see	Table	1).	Women	with	PCOS	can	present	with	various	different	menstrual	symptoms	including	amenorrhea:	the	absence	of	menstruation	for	greater	than	three	cycles	in	a	previously	menstruating	woman,	or	the	absence	of	menstruation	greater	than	six	months	in	woman	with	previously	abnormal	menstruation	(Andreeff,	2014);	oligomenorrhea:	persistent	menstrual	cycles	≥45	days	(Villarroel,	et	al.,	2015);	or	regular	menses:	average	28	days,	ranges	from	24-35	days	(Jean	Hailes	for	Women’s	Health,	2015).	According	to	the	Rotterdam	criteria,	it	is	possible	for	a	woman	to	continue	to	have	regular	menstruation	and	still	be	diagnosed	with	PCOS;	however,	the	presence	of	amenorrhea	or	oligomenorrhea,	assist	in	making	the	diagnosis	of	PCOS	(Rotterdam,	2004).			 Hyperandrogenism	is	another	one	of	the	three	diagnostic	features	of	PCOS	(see	Table	1).	Although	present	in	approximately	60-80%	of	cases,	hyperandrogenism	can	sometimes	be	difficult	to	establish	(Jean	Hailes	for	Women’s	Health,	2015).	It	can	either	be	determined	by	physical	characteristics	of	hyperandrogenemia,	such	as	hirsutism,	acne,	and	androgenic	alopecia,	or	by	monitoring	laboratory	values	of	serum	androgen	levels	(Rotterdam,	2004).	Although	hirsutism	remains	the	most	reliable	indictor	of	clinical	hyperandrogenism,	it	is	still	difficult	to	use	as	a	diagnostic	measure	due	to	normal	variations	in	race	with	South	Asian	and	Mediterranean	populations	having	a	greater	degree	and	Asian	populations	having	a	lesser	degree	of	non-pathological	hirsutism.	It	is	also	a	highly	subjective	measure	and	even	with	the	use	of	grading	tools	such	as	the	Ferriman-Galleyway	Hirsutism	Scale	(Bode,	Seehusen,	&	Baird,	2012),	to	objectify	the	symptoms,	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  14 accuracy	remains	difficult	(Rotterdam,	2004).	Acne	and	androgenic	alopecia	can	also	develop	in	women	with	PCOS	as	a	result	of	hyperandrogenemia;	however,	these	measures	are	less	well	studied	and	the	existing	literature	is	somewhat	conflicting	so	therefore	should	not	be	used	as	a	measure	of	hyperandrogenism	(Rotterdam,	2004).			 Serum	androgens	are	a	better	indicator	of	hyperandrogenemia,	however	diagnosis	is	still	challenging	based	on	available	laboratory	technology	and	tests	used.		Testosterone	measurements	are	often	designed	for	use	in	males,	resulting	in	decreased	accuracy	when	assessing	for	female	levels.	Also,	if	a	woman	is	taking	an	oral	contraceptive	pill,	or	has	not	been	off	of	it	for	at	least	3	months,	results	may	be	inaccurate	(Jean	Hailes	for	Women’s	Health,	2015).	Regardless	of	these	controversies,	serum	androgens	can	still	give	an	indication	of	the	presence	and	degree	of	hyperandrogenemia	and	can	be	ordered	to	rule	in	a	diagnosis	of	PCOS	based	on	patient	presentation	of	clinical	hyperandrogenism,	amenorrhea,	or	infertility.	First	line	laboratory	tests	that	should	be	considered	by	the	NP	include	total	and	free	testosterone	(Jean	Hailes	for	Women’s	Health,	2015).	The	specialist	may	consider	additional	testing	once	referral	is	made.		 If	the	above	two	diagnostic	criteria	are	positive,	identification	of	polycystic	ovaries	by	ultrasound	is	not	necessary	for	a	diagnosis	of	PCOS	(see	Table	1).	However,	performing	a	pelvic	ultrasound	can	be	beneficial	in	confirming	the	presence	of	polycystic	ovaries	as	well	as	assessing	for	endometrial	hyperplasia	and	potential	risk	of	endometrial	cancer	(Rotterdam,	2004).	Polycystic	ovaries	are	detected	by	ultrasound,	either	transvaginally	or	transabdominally.	Transvaginal	ultrasound	provides	more	accurate	detection	of	the	presence	of	polycystic	ovaries,	but	should	not	be	performed	in	adolescents	who	have	not	yet	become	sexually	active	(Jean	Hailes	for	Women’s	Health,	2015).	As	described	by	the	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  15 various	different	phenotypes	of	PCOS,	polycystic	ovaries	are	often,	but	not	always	present	in	women	with	PCOS.	The	physical	appearance	of	an	ovary	affected	by	PCOS	is	described	as	multiple	cyst-like	structures.	These	‘cysts’	are	immature	follicles	that	have	not	had	the	chance	to	fully	develop.	Detection	of	immature	follicles	on	ultrasound	can	be	a	normal	finding	in	many	women;	however,	is	considered	pathological	based	on	the	number	of	cysts	that	present	(Dewailly	et	al.,	2014).	The	current	accepted	diagnostic	criteria	for	PCOS	defines	polycystic	ovaries	as	the	presence	of	≥12	follicles	in	a	single	ovary,	measuring	2-9mm;	and/or,	ovarian	volume	>10ml	(Rotterdam,	2004).	Since	the	Rotterdam	criteria	were	established,	controversy	has	arisen	regarding	the	use	of	≥12	follicles	as	a	cut	off	due	to	advancements	in	technology	and	greater	ease	at	identifying	follicles	on	ultrasound,	subsequently	leading	to	over	diagnosis	of	PCOS.	In	2014,	the	Androgen	Excess	and	Polycystic	Ovary	Syndrome	Society	published	a	task	force	report,	which	analyzed	the	current	literature	and	made	a	recommendation	that	the	diagnostic	criteria	for	the	number	of	follicles	present	should	be	increased	to	≥25	follicles.	If	using	ovarian	volume	to	diagnose	PCOS	in	cases	of	poor	image	quality	and	inability	to	identify	individual	follicles,	the	volume	of	≥10ml	is	still	recommended	(Dewailly	et	al.,	2014).	Diagnostic	controversy.	Controversy	exists	regarding	the	diagnosis	and	management	of	PCOS,	primarily	due	to	the	discrepancies	in	the	three	different	versions	of	the	diagnostic	criteria.	In	2012,	a	National	Institutes	of	Health	workshop	on	PCOS	took	place	and	the	experts	proposed	many	recommendations	in	order	to	clarify	the	syndrome	(National	Institutes	of	Health,	2012).	Included	in	these	recommendations	was	the	universal	adoption	of	the	Rotterdam	criteria	for	diagnosis	due	to	its	broad,	inclusionary	conditions.	By	adopting	a	widely	accepted	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  16 definition	of	PCOS,	diagnosis	becomes	less	complicated	and	treatment	is	more	easily	managed	(National	Institutes	of	Health,	2012).	Experts	also	believe	that	the	name	PCOS	is	distracting	because	it	focuses	on	the	presence	of	polycystic	ovaries,	which	are	not	necessary,	nor	sufficient	on	their	own,	to	diagnose	the	syndrome	(National	Institutes	of	Health,	2012).	PCOS	and	Insulin	Resistance	What	is	Insulin	and	Insulin	Resistance?	Insulin	is	a	hormone	secreted	by	the	pancreas	that	assists	in	regulating	the	production,	absorption,	and	utilization	of	glucose,	thus,	ensuring	maintenance	of	steady	glucose	levels	(Moller	&	Flier,	1991).	Insulin	resistance	(IR)	can	be	defined	as	a	subnormal	biological	response	to	normal	levels	of	insulin	and	can	occur	in	various	target	areas	of	the	body	such	as	the	muscles,	liver,	and	brain.	When	left	unmanaged,	it	can	quickly	develop	into	more	severe	disorders	such	as	metabolic	syndrome	or	diabetes	mellitus	type	2		(DM2)	(Mantzoros,	2015).		Insulin	Resistance	and	PCOS	Polycystic	ovary	syndrome	has	numerous	impacts	on	the	metabolic	functioning	of	women	with	this	disorder,	particularly	with	an	increased	prevalence	of	IR,	metabolic	syndrome,	and	DM2.	Though	not	all	women	with	PCOS	suffer	from	IR,	studies	estimate	between	65%-80%	of	women	with	PCOS	are	resistant	to	insulin,	depending	on	the	diagnostic	criteria	used	(Jean	Hailes	for	Women’s	Health	Foundation,	2015).	Although	IR	is	commonly	associated	with	obesity	in	individuals	without	PCOS,	IR	in	PCOS	seems	to	be	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  17 prevalent	regardless	of	level	of	obesity.	Obese	woman	with	PCOS	are	seen	to	have	a	3	to	4	fold	increase	in	DM2	and	lean	women	with	PCOS	are	seen	to	have	a	2	to	3	fold	increase	in	the	prevalence	of	DM2	(Wang	et	al.,	2011).	Another	multi-site,	longitudinal	study	evaluated	2543	women	with	the	phenotypic	presentation	of	androgen	excess	coupled	with	menstrual	irregularity:	phenotype	A	and	B	(Table	2),	and	found	that	these	women	were	at	higher	risk	for	metabolic	syndrome	compared	to	the	control	group	(Polotsky,	et	al.,	2012).	Results	of	these	studies	suggest	that	PCOS	is	an	independent	risk	factor	for	the	development	of	IR	and	the	subsequent	development	of	DM2	should	be	closely	monitored.		Recommendations	within	these	studies	are	congruent	with	the	suggestions	made	by	Fauser	et	al.,	(2012),	who	advise	biochemical	screening	for	IR	in	women	with	PCOS	who	fit	the	following	criteria:	“hyperandrogenism	with	anovulation,	acanthosis	nigricans,	obesity	(BMI>	30	kg/m2,	or	>25	in	Asian	populations),	in	women	with	a	family	history	of	T2D	[diabetes	mellitus	type	2]	or	GDM	[gestational	diabetes]”	(Fauser	et	al.,	2012,	p.	34).		Throughout	the	literature	reviewed,	it	is	evident	that	the	most	useful	test	for	screening	and	monitoring	IR	is	with	an	oral	glucose	tolerance	test	(OGTT)	since	approximately	80%	of	cases	of	prediabetes	can	be	missed	with	other	tests	such	as	a	fasting	blood	sugar	level	(Jean	Hailes	for	Women’s	Health,	2015).	The	OGTT	involves	fasting	blood	work	and	hourly	interval	testing	of	blood	glucose	levels	for	2	hours	following	a	challenge	of	75-gram	oral	glucose	ingestion	(Stovall,	Bailey,	&	Pastore,	2011).	This	should	be	done	at	onset	of	initial	diagnosis	for	PCOS	and	continue	every	two	years	for	the	duration	of	the	woman’s	life	(Jean	Hailes	for	Women’s	Health,	2015).		Conclusions	from	analyzing	the	literature	support	monitoring	for	and	treating	insulin	resistance	in	the	long-term	management	of	women	with	PCOS.	Understanding	the	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  18 prevalence	of	IR	among	women	with	PCOS	can	assist	in	decisions	about	the	necessity	of	universal	screenings	and	can	also	help	target	women	at	high	risk	for	IR	and	prevent	long-term	complications.		Recommendations		Recommendations	regarding	screening	and	monitoring	were	ascertained	throughout	review	of	the	current	literature.	Screening	for	IR	includes	a	2hr	75g	OGTT	at	onset	of	initial	diagnosis	of	PCOS	and	every	two	years	for	the	duration	of	the	woman’s	life.	Women	should	be	screened	annually	if	they	possess	risk	factors	for	the	development	of	DM2,	such	as:	hyperandrogenism	with	anovulation,	acanthosis	nigricans,	obesity	(BMI>	25	kg/m2),	ethnicity	(Aboriginal,	Hispanic,	South	Asian,	Asian,	or	African	descent),	parental	history	of	diabetes,	history	of	high	blood	glucose	levels,	or	physical	inactivity	(Jean	Hailes	for	Women’s	Health,	2015).		First	line	treatment	for	diabetes	is	metformin.	When	starting	women	with	PCOS	on	metformin,	it	is	important	to	note	that	additional	benefits	include	the	reduction	of	androgen	levels	as	well	as	regulation	of	menstruation	(Barthelmess	&	Naz,	2015).	Prescribing	of	metformin	can	be	considered	by	the	primary	care	NP,	either	alone,	or	in	collaboration	with	the	endocrinologist,	for	regulating	sugar	levels	as	well	as	reducing	other	symptoms	of	PCOS.		Management	Guidelines	1. Screening	for	IR	with	a	2-hr	75g	OGTT	is	recommended	in	women	with	PCOS	at	onset	of	diagnosis	and	every	two	years	thereafter.	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  19 2. Screening	with	a	2-hr	75g	OGTT	should	be	performed	every	year	if	the	patient	possesses	the	following	risk	factors	(Ekoé,	Punthakee,	Ransom,	Prebtani,	&	Goldenberg,	2013;	Jean	Hailes	for	Women’s	Health,	2015):	• PCOS	presentation:	hyperandrogenism	with	anovulation		• Acanthosis	nigricans	• Obesity	(BMI>	25	kg/m2)	• Ethnicity:	Aboriginal,	Hispanic,	South	Asian,	Asian,	or	African	descent	• Parental	history	of	diabetes	• History	of	high	blood	glucose	levels	• Physical	inactivity	3. Treatment	of	elevated	blood	sugar	levels	should	start	with	metformin	250-500mg	PO	BID	(BC	Guidelines,	2015b).		4. If	not	being	followed	by	endocrinology	already,	the	patient	should	be	referred	to	endocrinology	at	onset	of	diagnosis	of	diabetes.		PCOS	and	Cardiovascular	Disease		 It	is	evident	throughout	the	literature	that	PCOS	is	associated	with	many	known	cardiovascular	disease	(CVD)	risk	factors;	however,	controversy	exists	regarding	a	direct	cause	and	effect	relationship	between	the	presence	of	PCOS	and	the	ultimate	development	of	CVD	(Bates	&	Legro,	2013).	Literature	suggests	the	cause	of	higher	prevalence	of	CVD	in	women	with	PCOS	is	related	to	life-long	metabolic	disturbances,	IR,	dyslipidemia,	hypertension,	abdominal	obesity,	depression,	and	sleep	apnea	(Bates	&	Legro,	2013),	(Chang	&	Wild,	2009).	Challenges	exist	however,	in	quantifying	CVD	risk	directly	from	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  20 PCOS	or	from	the	common	accompanied	manifestations	because	PCOS	is	predominantly	a	pre-menopausal	syndrome	(Chang	&	Wild,	2009).	Diagnosis	of	PCOS	typically	does	not	occur	after	menopause	(Legro	et	al.	2013)	because	androgen	excess	diminishes	and	polycystic	ovaries	regress	after	menopause.	Conversely,	cardiovascular	events	are	much	more	common	in	postmenopausal	women	(Chang	&	Wild,	2009).	Some	studies	have	used	markers	of	cardiovascular	risk	in	order	to	predict	potential	for	CVD	risk	in	women	with	PCOS.	These	markers	include	coronary	artery	calcification,	peripheral	endothelial	reactivity,	and	carotid	intima-media	wall	thickness.	Chang	and	Wild	(2009),	provide	a	review	of	the	studies	which	have	used	the	previously	mentioned	cardiac	risk	markers;	however,	results	presented	by	Chang	and	Wild	(2009)	remain	inconclusive	regarding	when	and	how	to	screen	women	with	PCOS	for	cardiovascular	disease.	The	recommendations	made	by	Fauser	et	al.	(2012),	state	that	coronary	artery	calcification	and	carotid	intima	media	wall	thickness	are	increased	in	PCOS	compared	to	control	groups,	independent	of	obesity	or	age	risk	factors.	Fauser	et	al.	(2012)	also	state	that	the	relationship	between	PCOS	and	cardiovascular	mortality	is	yet	to	be	determined	and	further	research	is	needed	to	make	a	recommendation	on	timing	and	frequency	of	screening	(Fauser	et	al.,	2012).	In	summarizing	recommendations	from	these	articles,	both	recognize	a	correlation	between	PCOS	and	cardiovascular	risk,	but	are	unable	to	determine	a	direct	cause	and	effect	relationship	between	PCOS	and	CVD	development	and	CVD	mortality.	The	Jean	Hailes	for	Women’s	Health	guideline	(2015),	on	the	other	hand,	recognizes	the	increased	prevalence	of	cardiac	risk	markers	in	women	with	PCOS	and	subsequently	suggests	recommended	screening.	Similarly	however,	they	also	struggled	to	find	evidence	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  21 to	prove	the	most	effective	screening	tool	or	method	of	assessing	CVD	risk.	They	suggest	that	women	with	the	following	risk	factors	should	be	screened	regularly	for	CVD:	“obesity,	cigarette	smoking,	dyslipidemia,	hypertension,	impaired	glucose	tolerance,	lack	of	physical	activity,	and	those	with	metabolic	syndrome	and/or	type	2	diabetes”	(Jean	Hailes	for	Women’s	Health,	2015,	p.14).	Recommended	screening	intervals	should	be	based	on	the	presence	of	any	of	the	above	risk	factors.		In	summary,	although	there	is	insufficient	evidence	regarding	a	direct	correlation	between	PCOS	and	the	development	of	cardiovascular	disease,	it	is	clear	that	by	reducing	risk	factors,	women	can	reduce	their	overall	CVD	risk.			Recommendations	Recommendations	for	reducing	the	risk	of	developing	CVD	in	women	with	PCOS	include	screening	for	the	following	CVD	risk	factors	at	every	visit:	“obesity,	cigarette	smoking,	dyslipidemia,	hypertension,	impaired	glucose	tolerance,	lack	of	physical	activity,	and	those	with	metabolic	syndrome	and/or	type	2	diabetes”	(Jean	Hailes	for	Women’s	Health,	2015,	p.14).	This	would	include	monitoring	waist	circumference	and	BMI,	current	smoking	and	exercise	habits,	monitoring	blood	pressure,	and	monitoring	lab	work	for	lipid	profiles	and	oral	glucose	tolerance	testing	(OGTT),	at	least	every	2	years	or	annually	if	risk	factors	present.		Management	Guidelines	1. Screening	for	CVD	should	be	performed	every	2	years	(Jean	Hailes	for	Women’s	Health,	2015).	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  22 2. If	risk	factors	present,	screening	should	be	performed	every	1	year	(Jean	Hailes	for	Women’s	Health,	2015).	3. Screening	includes	monitoring	for	the	presence	of	CVD	risk	factors	and	entails	assessing:	• Waist	circumference:	target	<88cm	(Goldenberg	&	Punthakee,	2013)	• 	BMI:	target	<25	kg/m2	(Jean	Hailes	for	Women’s	Health,	2015)	• Smoking	status:	goal	is	reduction	or	quitting	smoking	(BC	Guidelines,	2014)	• Exercise	habits:	goal	is	30	min	of	moderate	to	vigorous	activity	5-7	days	a	week	(BC	Guidelines,	2014)	• Blood	pressure:	target	<140/90	or	<130/90	if	diabetic	(BC	Guidelines,	2015a)	• Lipid	profiles:	aim	is	LDL	<3.5	(BC	Guidelines,	2014)	• OGTT:	target	<11.0	(Ekoé,	et	al.,	2013)	4. Women	with	high	blood	pressure	or	hyperlipidemia	should	be	treated	appropriately	by	the	NP	according	to	BC	Guideline	recommendations	(BC	Guidelines,	2014).	5. Counselling	for	smoking	cessation	strategies	should	be	provided	for	women	who	smoke.	Resources	to	offer	include	www.quitnow.ca	(BC	Guidelines,	2014).	6. Referral	to	a	cardiologist	should	be	considered	to	optimize	patient	care	(Jean	Hailes	for	Women’s	Health,	2015).	PCOS	and	Cancer	Risk		 The	strength	of	the	association	between	endometrial	cancer	risk	and	PCOS	remains	controversial;	however,	many	studies	and	review	articles	do	recognize	a	relationship	between	these	two	factors.	One	meta-analysis	by	Chittenden,	Fullerton,	Maheshwari,	and	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  23 Bhattacharya,	(2009),	suggest	that	women	with	PCOS	are	three	times	more	likely	to	develop	endometrial	carcinoma	than	women	who	do	not	have	PCOS.	Women	with	PCOS	are	at	higher	risk	for	developing	endometrial	cancer	due	to	chronic	oligoovulation	or	anovulation,	which	results	in	endometrial	hyperplasia	and	progression	to	endometrial	cancer	(Chittenden	et	al.,	2009).	Additionally,	many	of	the	clinical	features	of	PCOS	are	also	shared	risk	factors	for	endometrial	cancer	such	as,	“obesity,	hypertension,	type	II	diabetes,	unopposed	oestrogen,	and	nulliparity”	(Chittenden	et	al.,	2009,	p.	398).	Since	the	time	the	Chittenden	et	al.,	article	was	written	in	2009,	Haoula,	(2012),	performed	a	meta-analysis,	which	critiqued	many	of	the	studies	done	on	PCOS	and	endometrial	cancer	risk	based	on	limitations	of	size	as	well	as	the	diagnostic	inclusion	criteria.	However,	despite	this	critique,	Haoula	still	discovered	a	3-fold	increase	in	the	risk	of	developing	endometrial	cancer	in	women	who	have	PCOS	(Haoula,	2012).	It	has	been	suggested	by	some	researchers	that	women	with	PCOS	are	also	at	higher	risk	of	developing	other	estrogen	dependent	cancers	such	as	breast	and	ovarian	cancer.	However,	a	meta-analysis	by	Barry,	Azizia,	and	Hardiman,	(2014),	did	not	find	sufficient	evidence	to	prove	a	link.	Similar	to	determining	CVD	risk,	defining	a	direct	cause	and	effect	relationship	between	PCOS	and	breast	and	ovarian	cancer	risk	is	complicated	by	other	clinical	features	of	PCOS,	most	notably	obesity	(Barry,	Azizia,	&	Hardiman,	2014).	Also	the	review	articles	that	Barry,	Azizia,	and	Hardiman,	(2014),	analyzed	have	shown	insufficient	evidence	to	prove	an	increased	risk	of	other	cancers	based	on	the	numbers	of	studies	reviewed	for	the	article	and	the	diagnostic	criteria	used.	Therefore,	based	on	the	literature	reviewed	for	this	paper,	a	conclusion	cannot	be	drawn	regarding	the	correlation	between	PCOS	and	either	breast	or	ovarian	cancer	risk	and	recommendations	for	screening	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  24 guidelines	cannot	be	made.		Recommendation		 Evidence	in	the	literature	reveals	a	link	between	PCOS	and	endometrial	cancer	with	an	almost	3-fold	increase	in	risk	compared	to	women	without	PCOS.	Since	there	are	no	screening	recommendations	for	monitoring	the	presence	of	endometrial	cancer,	clinical	guidelines	should	recommend	ordering	diagnostics,	such	as	ultrasound	and	endometrial	biopsy,	based	on	clinical	presentation	(Fauser	et	al.,	2012).	This	would	include	length	of	time	of	amenorrhea	and	any	abnormal	uterine	bleeding	(Fauser	et	al.,	2012),	coupled	with	the	presence	of	risk	factors	such	as:	“obesity,	hypertension,	type	II	diabetes,	unopposed	oestrogen,	and	nulliparity”	(Chittenden	et	al.,	2009,	p.	398).			 Treatment	recommendations	include	both	non-pharmacological	and	pharmacological	therapies.	Non-pharmacological	management	to	reduce	endometrial	cancer	risk	includes	diet	and	exercise	regimens.		Studies	report	regulation	of	ovulation	and	menstruation	in	women	who	have	lost	as	little	as	5%	of	their	total	body	weight	(Tarlatzis	et	al.,	2008).	Goal	for	diet	and	exercise	management	should	be	directed	at	losing	approximately	5-10%	body	weight	(Jean	Hailes	for	Women’s	Health,	2015).	Pharmacologic	treatments	to	regulate	menstruation	and	reduce	cancer	risk	involve	initiation	of	combination	oral	contraceptives	(COC).	Unless	imminent	desire	for	pregnancy	is	involved,	the	initiation	of	COC	can	help	balance	the	unopposed	estrogen	seen	in	PCOS	and	regulate	menstruation	(Legro	et	al.,	2013).	Low-dose	COCs	are	proven	to	be	more	effective	than	higher	dose	COCs	in	managing	the	other	associated	manifestations	of	PCOS	(Jean	Hailes	for	Women’s	Health,	2015).	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  25 Management	Guidelines	Management	goals	are	based	upon	reducing	risk	factors	for	the	development	of	cancer.	1. Women	with	PCOS	should	have	a	menstrual	bleed	at	least	4	times	every	year	(Chittenden	et	al.,	2009).	2. First	line	treatment	for	amenorrhea	in	order	to	reduce	the	risk	of	endometrial	cancer	includes	lifestyle	management	such	as	diet	and	exercise	with	a	goal	weight	loss	of	5-10%	body	weight	(Klein	&	Poth,	2013).	3. Pharmacologic	treatments	include	initiation	of	low-dose	combination	oral	contraceptives	to	regulate	hormone	levels	(Jean	Hailes	for	Women’s	Health,	2015).	4. Referral	to	gynecology	should	be	considered	in	women	with	persistent	oligo-menorrhea	or	amenorrhea	who	are	not	menstruating	at	least	4	times	per	year.	PCOS	and	Obesity	It	is	estimated	that	38-88%	of	women	with	PCOS	are	overweight	or	obese	(Barber,	McCarthy,	Wass,	&	Franks,	2006);	however,	exact	numbers	are	difficult	to	obtain	due	to	a	lack	of	representative	data	on	this	measure	(Lim,	Norman,	Davies,	&	Moran,	2013).	A	review	article	by	Barber,	et	al.	(2006),	evaluates	studies	that	show	a	strong	correlation	between	obesity	and	the	severity	of	PCOS	symptoms,	such	as	menstrual	irregularities,	hirsutism,	and	infertility.	This	was	demonstrated	by	noting	the	reduction	in	severity	of	PCOS	symptoms	as	a	result	of	weight	reduction.	Many	studies	indicate	that	even	a	5%	reduction	in	weight	can	result	in	return	of	menstruation	and	improvement	of	symptoms	of	hyperandrogenemia	(Barber	et	al.,	2006).		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  26 It	is	possible	for	lean	women	to	also	suffer	from	PCOS,	so	even	though	obesity	and	PCOS	are	strongly	correlated,	obesity	is	not	always	necessary	for	the	development	of	the	syndrome	(Barber	et	al.,	2006).	Therefore,	it	would	be	incorrect	to	assume	that	obesity	causes	PCOS;	yet,	there	is	evidence	in	the	literature	to	suggest	that	obesity	worsens	the	androgenic,	reproductive,	and	metabolic	symptoms	(Barber	et	al,	2006).	Conversely,	an	in	depth	meta-analysis	by	Lim	et	al.,	(2013)	state	that	obesity	only	had	significant	detrimental	effects	on	reproductive	and	metabolic	aspects	of	PCOS	and	made	no	difference	to	total	testosterone,	hirsutism,	or	cholesterol	levels.	This	meta-analysis	was	performed	after	researchers	noticed	conflicting	information	in	the	current	literature	regarding	the	impact	of	obesity	on	PCOS	(Lim	et	al.,	2013).	It	is	known	that	being	overweight	has	negative	impacts	on	many	aspects	of	the	overall	health	of	a	woman	with	PCOS,	and	being	obese	or	morbidly	obese	increases	these	impacts.	Further	research	is	required	to	determine	exact	cut-off	ranges	for	the	degree	of	obesity	that	causes	detrimental	effects,	as	well	as	the	ability	to	quantify	psychological	factors	that	contribute	to	obesity	(Lim	et	al.,	2013).		Recommendations		 Further	research	is	needed	to	pinpoint	specifics;	however,	for	the	overall	health	of	the	woman,	lifestyle	changes	are	recommended	for	overweight	or	obese	women,	aiming	for	5-10%	loss	of	current	body	weight	(Lim	et	al.,	2013).	Jean	Hailes	for	Women’s	Health	guidelines	recommend	lifestyle	modifications	to	lessen	the	severity	of	PCOS	symptoms	in	women	who	are	overweight	or	obese	(see	Table	3)	(Jean	Hailes	for	Women’s	Health,	2015).	Weight	loss	is	also	known	to	have	positive	impacts	on	mood,	quality	of	life,	fertility,	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  27 cardiovascular	health,	and	metabolic	consequences	of	PCOS	(Jean	Hailes	for	Women’s	Health,	2015).			According	to	the	BC	Guideline	document	entitled	Overweight	and	Obese	Adults:	Diagnosis	and	Management	lifestyle	management	is	recommended	for	women	in	obesity	class	1;	however,	for	women	in	obesity	class	2	or	3,	lifestyle	management	may	be	an	adjunct	to	more	aggressive	treatments	such	as	pharmacologic	or	surgical	interventions	(BC	Guidelines,	2011).	Also,	women	with	comorbidities	such	as	type	2	diabetes,	hypertension,	CVD,	osteoarthritis,	dyslipidemia,	and	sleep	apnea,	require	more	intensive	interventions	since	these	other	conditions	will	also	get	better	as	a	result	of	weight	loss	(BC	Guidelines,	2011).	Management	Guidelines	1. Weight,	height,	BMI	calculation,	and	waist	circumference	should	be	obtained	at	each	annual	or	biennial	visit.	2. Target	waste	circumference	is	<88cm	and	target	BMI	is	<25	kg/m2,	see	table	3	(BC	Guidelines,	2011).	3. In	the	overweight	or	obese	population,	the	NP	should	provide	adequate	diet	and	exercise	counselling	regarding	lifestyle	measures	to	reduce	obesity	and	increase	exercise	habits.	The	NP	should	stress	that	even	a	5%	reduction	in	weight	assists	in	return	of	menstruation	and	improvement	of	symptoms	of	hyperandrogenemia	(Barber	et	al.,	2006).	4. Obesity	class	1:	Lifestyle	management	is	recommended	(BC	Guidelines,	2011).	5. Obesity	class	2	or	3,	or	women	with	comorbidities	such	as	type	2	diabetes,	hypertension,	CVD,	osteoarthritis,	dyslipidemia,	and	sleep	apnea:	more	intensive	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  28 interventions	such	as	lifestyle	management	in	combination	with	pharmacologic	or	surgical	interventions	is	recommended	(BC	Guidelines,	2011).	6. Strategies	for	non-pharmacologic	weight	reduction	include	(BC	Guidelines,	2011):	a. Caloric	restriction	of	500-1000kcal/day	b. Physical	activity:	30+	minutes	of	moderate	to	vigorous	physical	activity	5-7	times	per	week	c. No	more	than	0.5-1kg/week	weight	loss	d. Establishing	initial	weight	loss	goal	of	5-10%	of	body	weight	e. Referral	to	weight	loss	program	and	support	groups	7. Pharmacologic	therapy	for	obesity	class	2	and	3	after	diet,	exercise,	and	behavioural	programs	have	failed:	orlistat	(Xenical)	(BC	Guidelines,	2011).	8. Referral	to	surgeon	for	gastric	bypass	surgery	if	unable	to	obtain	or	maintain	weight	reduction	strategies	Table	3:	BMI	Ranges	 		Weight	Classification	 BMI	(kg/m2)	Underweight	 <18.5	Normal	 18.5-24.9	Overweight	 25-29.9	Obese:	Class	1	 30-34.9	Obese:	Class	2	 35-39.9	Obese:	Class	3	 ≥	40				(adapted	from	BC	Guidelines,	2011)	PCOS	and	Mental	Health		 Depression	and	anxiety	are	two	conditions	that	women	with	PCOS	often	face.	The	largest	meta-analysis	done	to	date	was	performed	by	Veltman-Verhulst,	Boivin,	Eijkemans,	&	Fauser	in	2012.	This	analysis	reviewed	28	studies	that	evaluated	women’s	reported	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  29 experiences	in	three	different	domains:	depression,	anxiety,	or	emotional-subscales	of	quality	of	life	(emoQoL).	Results	of	this	study	show	that	women	with	PCOS	experience	significantly	greater	emotional	distress	than	control	women	within	all	three	domains	(Veltman-Verhulst	et	al.,	2012).	The	studies	do	not	give	explicit	explanations	regarding	the	cause	of	this	emotional	distress;	however,	they	propose	that	stigmatizing	factors	such	as	infertility,	hirsutism,	and	obesity	contribute.	Interestingly,	subgroup	analysis	results	indicate	that	emotional	distress	was	seen	in	lean,	fertile	women	with	PCOS,	as	well	as	in	obese,	infertile	women	with	PCOS,	suggesting	that	the	cause	of	emotional	distress	in	PCOS	is	multifactorial	and	not	solely	due	to	the	physical	manifestations	of	the	syndrome	(Veltman-Verhulst	et	al.,	2012).	Authors	of	this	meta-analysis	suggest	that	further	studies	are	required	to	determine	the	cause	of	emotional	distress	and	investigate	the	correlation	between	these	two	conditions	(Veltman-Verhulst	et	al.,	2012).			 The	consensus	document	written	by	Fauser	et	al.	(2012),	supports	the	information	gathered	by	Veltman-Verhulst	et	al.,	(2012).	Fauser	et	al.	(2012)	specifically	comment	that	women	with	PCOS	are	in	a	high-risk	group	for	reduced	quality	of	life	due	to	psychological	and	behavioral	disorders.	Some	of	the	studies	evaluated	in	this	article	used	a	screening	tool	called	the	QOL	Questionnaire	for	Women	with	PCOS	(PCOSQ),	which	is	the	only	validated	disease-specific	screening	tool	for	PCOS.	Results	of	studies	that	use	this	tool	show	that	PCOS	has	substantial	unfavorable	effects	on	quality	of	life,	most	often	due	to	weight	management	issues	(Fauser	et	al.,	2012).			 Evidenced	based	guidelines	by	the	Jean	Hailes	for	Women’s	Health	organization	(2015),	also	comment	on	the	correlation	between	emotional	distress	and	PCOS.	They	state,	that	the	prevalence	of	depression	in	women	with	PCOS	is	28%-64%	compared	to	7.1%-8%	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  30 in	the	general	population	and	prevalence	of	anxiety	in	PCOS	is	34%-57%,	compared	to	18%	in	the	general	population.	Also,	when	experienced,	depression	and	anxiety	were	more	severe	in	women	with	PCOS	compared	to	the	general	population.	Similarly,	they	state	that	the	cause	is	likely	multi-factorial,	ranging	from	physical	and	biochemical	factors	to	the	chronic	and	complex	nature	of	the	syndrome	(Jean	Hailes	for	Women’s	Health,	2011).		Recommendations		 All	three	of	the	meta-analyses	and	consensus	documents	reviewed	above,	offer	similar	recommendations	in	regards	to	screening	for	emotional	distress	and	decreased	quality	of	life.	Early	and	regular	screening	is	important	to	monitor	for	risk	and	progression	of	psychological	disorders	related	to	PCOS.		Veltman-Verhulst	et	al.,	(2012),	recommends	that	instead	of	using	a	specific	screening	tool,	practitioners	should	have	a	discussion	with	their	patients	regarding	their	current	moods	and	state	of	emotional	distress.	Discussions	with	patients	provide	an	opportunity	to	investigate	current	emotional	states	as	well	as	a	chance	to	offer	education	regarding	potential	emotional	impacts	in	the	future.	By	administering	a	screening	tool	at	a	single	point	in	time,	some	women	who	are	at	risk	for	developing	depression	or	anxiety	in	the	future	can	be	missed	(Veltman-Verhulst	et	al.,	2012).			 The	Jean	Hailes	for	Women’s	Health	guideline	section	on	depression	and	anxiety	recommends	three	screening	questions	that	can	be	asked	at	every	visit.	If	any	of	these	screening	questions	indicate	the	presence	or	potential	for	depression	or	anxiety,	disease	specific	screening	questionnaires	can	then	be	administered,	including	either	one	or	more	of	the	following:	Kessler	Psychological	Distress	Scale	10	(K-10),	Depression	Anxiety	Stress	Scale	(DASS-21),	Patient	Health	Questionnaire	(PHQ9),	or	Generalized	Anxiety	Disorder	7	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  31 item	scale	(GAD7).	Referral	to	a	psychiatrist	is	also	recommended	for	further	assessment	and	management	as	felt	appropriate	by	the	primary	care	provider	(Jean	Hailes	for	Women’s	Health,	2015).	Similarly,	the	BC	Guidelines	recommend	two	open-ended	questions	to	screen	for	and	detect	the	presence	of	emotional	distress.		Answering	yes	to	either	one	of	these	questions	prompts	further	investigation	into	type	and	degree	of	emotional	distress.	The	BC	Guidelines	questions	include:	“Have	you	lost	interest	or	pleasure	in	things	you	usually	like	to	do?	Have	you	felt	sad,	low,	down,	depressed	or	hopeless?”	(BC	Guidelines,	2013,	p.	1).	Management	Guidelines	1. NPs	should	have	discussions	with	their	patients	regarding	moods	and	quality	of	life	and	screen	for	the	presence	of	emotional	distress	with	every	annual	or	biennial	visit.	2. Women	with	PCOS	should	be	screened	for	emotional	distress	with	the	following	two	questions	(BC	Guidelines,	2013):		In	the	past	month:		I. Have	you	lost	interest	or	pleasure	in	things	you	usually	like	to	do?	II. Have	you	felt	sad,	low,	down,	depressed	or	hopeless?		3. If	a	woman	answers	yes	to	either	question,	further	screening	is	recommended	with	the	PHQ-9	(Appendix	A)	or	the	GAD-7	questionnaire	(Appendix	B)	4. NPs	should	refer	to	the	BC	Guideline	for	full	management	guidelines:	http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/depression_full_guideline.pdf	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  32 PCOS	and	Infertility	The	American	Academy	of	Family	Practice	defines	infertility	as,	“the	inability	to	achieve	pregnancy	after	one	year	of	regular,	unprotected	intercourse”	(Lindsay	&	Vitrikas,	2015,	p.	308),	however,	women	who	are	older	than	35	years	of	age	are	considered	infertile	after	6	months	of	unprotected	intercourse	(Lindsay	&	Vitrikas,	2015).	Many	women	with	PCOS	experience	infertility	secondary	to	ovulatory	dysfunction	and	endometrial	receptivity	(Ecklund	&	Usadi,	2015).	Infertility	is	further	exacerbated	by	the	presence	of	obesity	and	insulin	resistance,	which	has	effects	on	the	granulosa	cells	in	the	ovaries	causing	premature	lutenization	and	subsequent	disruption	of	normal	oocyte	maturation	(Ecklund	&	Usadi,	2015).			 Although	the	NP	cannot	treat	or	manage	infertility,	preconception	counselling	and	initial	investigations	can	take	place	in	the	primary	care	setting.	Preconception	counselling	should	include	discussions	regarding	limitation	or	avoidance	of	factors	that	can	contribute	to	infertility,	such	as,	smoking	and	excessive	alcohol	consumption,	as	well	as	discussion	and	education	regarding	frequency	of	intercourse.	Recommendations	include	having	unprotected	intercourse	every	1-2	days	around	the	time	of	ovulation	(Lindsay	&	Vitrikas,	2015).	Weight	loss	remains	first–line	therapy	for	treatment	of	infertility	in	women	with	PCOS	(Tarlatzis	et	al.,	2008).		The	NP	can	initiate	counselling	and	monitoring	of	lifestyle	management	and	assist	in	goal	setting	for	weight	loss.	According	to	Tarlatzis	et	al.,	(2008),	women	who	have	lost	as	little	as	5%	of	their	total	body	weight	often	report	spontaneous	return	of	ovulation	and	subsequent	successful	pregnancies	(Tarlatzis	et	al.,	2008).		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  33 Weight	loss	counselling	should	include	both	diet	and	exercise	regimens	(Jean	Hailes	for	Women’s	Health,	2015).	Diet	considerations	include	a	calorie-restricted	diet	with	reduced	glycemic	load.	This	will	not	only	assist	with	infertility	due	to	weight	loss,	but	also	has	a	positive	impact	on	reducing	hyperinsulinemia	and	its	metabolic	consequences,	one	of	which	being	infertility	(Tarlatzis	et	al.,	2008).	With	the	exception	of	the	above	recommendations,	very	few	studies	have	been	done	to	evaluate	which	diet	in	particular	is	most	beneficial	and	within	those,	no	consensus	has	been	drawn	regarding	the	optimal	diet	for	women	with	PCOS	(Tarlatzis	et	al.,	2008).	Nutrition	counseling	by	the	primary	care	provider	and	referral	to	dietitian	can	assist	patients	in	optimizing	initial	weight	loss	and	strategies	on	maintaining	this	throughout	life	(BC	Guidelines,	2011).		Exercise	is	also	recommended	for	obese	women	with	PCOS	to	assist	in	weight	loss;	noting	that	individual	considerations	must	be	made	for	many	women	in	regards	to	cardiovascular	and	musculoskeletal	health	when	initiating	any	exercise	regimen.	Studies	have	not	shown	exercise	alone	to	be	overly	beneficial	in	providing	significant	weight	loss;	however,	when	coupled	with	diet,	better	initial	and	long-term	weight	loss	management	is	obtained	(Tarlatzis	et	al.,	2008).	The	Jean	Hailes	for	Women’s	Health	guideline	(2015)	recommends	not	offering	pharmacologic	therapy	for	ovulation	induction	in	women	who	have	a	BMI	≥35	until	3-6	months	of	lifestyle	interventions	of	diet	and	exercise	have	been	trialed	or	the	patient	has	undergone	bariatric	surgery	(Jean	Hailes	for	Women’s	Health,	2015).	NPs	can	assist	in	this	aspect	of	care	by	initiating	discussion	about	weight	loss	management,	reviewing	the	benefits	of	weight	loss	when	trying	to	conceive,	and	initiating	referrals	to	dieticians,	exercise	therapists,	or	surgeons.		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  34 Recommendations		Preconception	counselling	is	one	of	the	main	areas	of	focus	in	which	NPs	can	assist	with	infertility	in	women	with	PCOS	(Tarlatzis	et	al.,	2008).	Initiation	of	lifestyle	management	with	a	goal	weight	loss	target	of	5-10%	body	weight	should	occur	prior	to	discussion	and	consideration	of	ovulation	induction	(Jean	Hailes	for	Women’s	Health,	2015).	Nurse	Practitioners	can	also	initiate	diagnostic	evaluation	prior	to	referral	to	an	infertility	specialist.	Workup	includes	laboratory	blood	tests	such	as	FSH,	LH,	progesterone,	estradiol,	prolactin,	and	TSH	(Lindsay	&	Vitrikas,	2015).	Referral	to	an	infertility	clinic	should	take	place	for	continuation	of	investigations,	if	necessary,	and	exploration	of	management	options.	Multiple	pharmacologic	options	are	available	to	assist	women	in	obtaining	a	successful	pregnancy;	however,	prescribing	these	medications	is	outside	the	NP	scope	in	British	Columbia	(College	of	Registered	Nurses	of	British	Columbia,	2016).	Women	with	PCOS	who	do	become	pregnant	require	close	monitoring	for	pregnancy	related	complications	as	they	are	at	higher	risk	for	gestational	diabetes	and	hypertensive	disorders	(Ecklund	&	Usadi,	2015).	It	is	outside	the	scope	of	the	NP	in	BC	to	deliver	babies,	therefore	referral	to	a	GP	or	to	an	obstetrician	for	delivery	needs	to	take	place	prior	to	28	weeks	gestation	(College	of	Registered	Nurses	of	British	Columbia,	2015).	Management	Guidelines	1. Lifestyle	management	for	weight	loss	is	first	line	treatment	for	infertility	in	obese	women	with	PCOS	and	should	be	trialed	for	3-6	months	prior	to	discussions	and	interventions	for	ovulation	induction	(Jean	Hailes	for	Women’s	Health,	2015).	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  35 2. Counselling	should	include	discussion	regarding	avoiding	factors	that	may	contribute	to	infertility	such	as:	smoking,	excessive	alcohol	use,	and	ensuring	the	couple	is	engaging	in	intercourse	at	least	every	1-2	days	around	the	time	of	ovulation.		3. Diagnostic	laboratory	workup	for	infertility	by	the	NP	includes:	FSH,	LH,	progesterone,	estradiol,	prolactin,	and	TSH	(Lindsay	&	Vitrikas,	2015).	4. Referral	to	an	infertility	specialist	should	occur	after	lifestyle	interventions	for	weight	loss	have	been	attempted	for	3-6	months	and	pregnancy	has	not	been	successful	(Jean	Hailes	for	Women’s	Health,	2015).	PCOS	and	Dermatology		 Androgens	play	an	important	role	in	the	disease	process	of	PCOS	as	well	as	in	the	clinical	manifestations	including:	hirsutism,	acne,	and	alopecia.	Another	dermatologic	manifestation	of	PCOS	is	acanthosis	nigricans	which	can	develop	as	a	result	of	insulin	resistance	(Housman	&	Reynolds,	2014).		Clinical	signs	of	hyperandrogenemia	are	very	common	in	PCOS	and	are	one	of	the	hallmark	diagnostic	features	of	the	syndrome.	Up	to	60%	of	women	with	PCOS	experience	hirsutism,	defined	as	excessive	male	pattern	terminal	body	hair	seen	in	women	(Bode	et	al.,	2012).	Although	hirsutism	can	differ	between	ethnicities,	it	remains	a	valid	physical	indicator	of	hyperandrogemia	(Housman	&	Reynolds,	2014).	Most	commonly,	this	is	seen	on	the	upper	lip,	chin,	areola,	chest,	back,	and	lower	abdomen.	Acne	is	another	common	manifestation	of	hyperandrogenism;	usually	seen	on	the	lower	face,	neck,	chest,	and	upper	back.	Varying	presentations	of	both	hirsutism	and	acne	can	be	attributed	to	the	activity	of	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  36 isoenzymes	and	the	sensitivity	of	androgen	receptors	and	is	not	always	directly	attributed	to	levels	of	serum	androgens	(Housman	&	Reynolds,	2014).	Androgenic	alopecia	can	also	be	seen	in	PCOS;	however,	is	much	less	common	than	hirsutism	and	acne.	Careful	history	and	physical	examination	assist	in	directing	the	diagnosis	of	alopecia	towards	androgenic	alopecia	or	other	causes	of	alopecia.	Laboratory	investigations	can	be	helpful	in	confirming	diagnosis	and	correlation	to	hyperandrogenism	(Thiedke,	2003).	Due	to	cultural	differences	of	hirsutism	in	women	with	and	without	PCOS,	monitoring	for	hirsutism	and	use	as	a	diagnostic	feature	can	be	challenging	(Housman	&	Reynolds,	2014).	The	Ferriman-Gallwey	scale	of	hirsutism	is	a	tool	that	attempts	to	objectify	this	very	subjective	symptom	by	grading	the	amount	of	hair	present	on	nine	different	body	parts	using	graphics.	These	body	parts	include	the	upper	lip,	chin,	chest,	abdomen,	pubic	area,	arms,	legs,	back,	and	buttocks	(Bode	et	al.,	2012).	Critics	of	this	tool	discuss	the	limitation	of	not	allowing	for	scoring	of	hair	in	other	body	parts	(eg.	side	burns).	However,	despite	its	limitations,	this	scale	remains	the	most	commonly	used	tool	to	score	hirsutism	(Bode	et	al.,	2012).	Recommendations		 Current	guidelines	by	Fauser	et	al.	(2012)	recognize	that	hirsutism	is	an	adequate	marker	for	hyperandrogenism;	however,	biochemical	hyperandrogenemia	should	also	be	evaluated	in	women	that	are	suspected	to	have	PCOS.	Conversely,	they	state	that	acne	and	alopecia	are	not	good	indicators	of	hyperandrogenemia	so	should	not	be	used	as	a	marker	of	clinical	hyperandrogenism	when	diagnosing	PCOS	(Fauser	et	al.,	2012).			 Treatment	regimens	should	be	based	on	clinical	presentation	and	patient	preference	for	ridding	excess	body	hair	or	treating	acne.	Treatment	for	hirsutism	is	focused	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  37 on	reducing	androgen	production,	decreasing	circulating	free	testosterone,	and	limiting	androgen	bioactivity	to	target	hair	follicles.	Interventions	for	hyperandrogenemia	focus	on	reducing	steroid	production	from	the	ovaries,	thus	reducing	bioavailabity.	Oral	contraceptive	pills	(OCP)	are	commonly	used	for	this	purpose,	either	alone,	or	in	combination	with	an	antiandrogen	such	as	spironolactone	(Fauser	et	al.,	2012).	Due	to	the	life	cycle	of	terminal	hair,	at	least	6	months	of	treatment	is	necessary	to	see	clinical	results	(Bode	et	al.,	2012).		Laser	therapy	may	be	recommended	but	is	expensive	and	time-consuming.	It	is	an	effective	measure	for	elimination	of	unwanted	body	hair,	so	can	be	recommended	to	patients	if	cost	is	not	a	factor	(Bode	et	al.,	2012).	Acne	can	be	treated	with	various	topical	or	systemic	acne	therapies	based	on	clinical	presentation	and	patient	preference	(Fauser	et	al.,	2012).	Topical	retinoids	remain	first	line	mono-therapy	for	treatment	of	non-inflammatory	acne,	and	can	be	used	in	combination	with	a	topical	antibiotic	for	inflammatory	acne	(Titus	&	Hodge,	2012).	Combination	oral	contraceptives	in	women	who	are	not	wishing	to	become	pregnant	can	also	be	very	effective	in	the	treatment	of	both	inflammatory	and	non-inflammatory	acne	(Titus	&	Hodge,	2012).	Management	Guidelines	1. Interventions	for	clinical	hyperandrogenemia	focus	on	reducing	steroid	production	from	the	ovaries,	thus	reducing	bioavailabity.		2. Oral	contraceptive	pills	are	commonly	used	for	clinical	hyperandrognemism,	either	alone,	or	in	combination	with	an	antiandrogen	such	as	spironolactone	(Fauser	et	al.,	2012).	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  38 3. Laser	therapy	is	an	effective	measure	for	elimination	of	unwanted	body	hair	but	is	expensive	and	time-consuming.	It	can	be	recommended	to	patients	if	cost	is	not	a	factor	(Bode	et	al.,	2012).	4. Acne	management	includes	assessment	and	determination	of	type	and	severity	of	acne.	First	line	treatment	options	include	combination	estrogen	and	progesterone	oral	contraceptive	pills,	or	topical	retinoid,	either	alone,	or	in	combination	with	a	topical	antibiotic	(Titus	&	Hodge,	2012).	Diagnostic	workup		 Initial	diagnostic	workup	for	the	woman	presenting	with	symptoms	suggestive	of	PCOS	is	somewhat	dependent	on	clinical	presentation.	According	to	the	Rotterdam	criteria,	in	order	to	make	a	diagnosis	of	PCOS,	certain	clinical	features	need	to	be	present	and	other	diseases	or	syndromes	need	to	be	ruled	out.	Therefore,	it	is	critical	that,	before	making	the	diagnosis	of	PCOS,	other	conditions	are	considered	and	a	thorough	diagnostic	workup	is	performed	(Rotterdam,	2004).		Other	Conditions	to	Rule	In	or	Rule	Out	The	NP	can	assist	in	narrowing	down	the	diagnosis	by	ordering	particular	diagnostic	tests	based	on	the	patient’s	presenting	complaint	and	clinical	picture.	Other	conditions	that	have	similar	clinical	manifestations	of	PCOS	include:	hyperthyroidism,	hyperprolactinemia,	21-hydroxylase-deficient	congenital	adrenal	hyperplasia,	Cushing’s	syndrome,	androgen	secreting	neoplasms,	and	idiopathic	hirsutism	(Azziz	et	al.,	2009).			 For	women	presenting	with	amenorrhea	or	oligomenorrhea,	diagnostics	would	be	indicated	to	rule	out	other	causes	such	as	pregnancy,	hyperandrogenemia,	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  39 hyperthyroidism,	hyperprolactinemia,	or	ovarian	insufficiency	(Barbieri	&	Ehrmann,	2015).	Table	4	provides	reference	ranges	for	normal	values	and	expected	results	to	rule	in	the	following	diseases.	Testing	to	rule	out	pregnancy	would	include	a	urine	or	serum	beta	hCG;	for	hyperthyroidism	a	thyroid	stimulating	hormone	(TSH)	level	and,	if	indicated	from	the	TSH,	a	Free	T4	level;	for	hyperprolactinemia,	a	serum	prolactin	level;	and	for	ovarian	insufficiency,	a	follicle	stimulating	hormone	(FSH)	level	(Barbieri	&	Ehrmann,	2015).			 For	a	patient	presenting	with	clinical	signs	of	hyperandrogenism,	it	would	be	necessary	to	rule	out	non-classic	congenital	adrenal	hyperplasia	(NCCAH),	Cushing’s	syndrome,	adrenal	tumors,	androgen-secreting	tumors,	or	ovarian	hyperthecosis	(Barbieri	&	Ehrmann,	2015).	NCCAH	is	due	to	a	deficiency	in	21-hydroxylase	and	can	be	ruled	out	by	measuring	a	morning	level	of	17-hydroxyprogesterone	(17-OHP)	in	the	early	follicular	phase.	It	is	more	prevalent	and	should	be	considered	more	seriously	in	certain	populations	such	as	women	of	Eastern	European	Jewish,	Hispanic,	Slavic,	or	Italian	decent	(Nieman	&	Merke,	2016).	Cushing’s	syndrome	may	have	many	of	the	same	symptoms	as	PCOS	such	as	hirsutism,	oligomenorrhea,	and	obesity;	however,	it	would	include	other	clinical	features	(such	as:	hypertension,	supraclavicular	fat	pads,	purple	abdominal	striae,	or	proximal	muscle	weakness)	that	are	not	present	in	PCOS	(Nieman,	2015).	Since	the	index	of	suspicion	for	Cushing’s	syndrome	is	low	based	on	the	absence	of	Cushing’s	specific	symptoms,	only	first	line	tests	are	indicated	in	ruling	out	the	diagnosis.	This	would	include	monitoring	24-hour	urinary	free	cortisol	(UFC)	excretion	(Nieman,	2015).	An	adrenal	tumor	should	be	ruled	out	by	checking	dehydroepiandrosterone	sulfate	(DHEA-S)	levels.	These	levels	would	be	markedly	elevated	in	the	presence	of	an	adrenal	tumor,	much	higher	than	what	is	seen	in	a	woman	with	PCOS	(Nieman,	2016).	A	woman	with	an	androgen	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  40 secreting	ovarian	tumor	or	ovarian	hyperthecosis	would	present	with	more	severe	signs	of	hyperandrogenism.	The	first	test	to	rule	this	out	would	be	a	total	testosterone	level.	If	this	is	significantly	higher	than	the	expected	range	for	PCOS,	these	diagnoses	could	be	considered	and	further	testing	can	be	done	to	confirm	(Barbieri	&	Ehrmann,	2015).			 In	addition	to	the	laboratory	tests	listed	above,	a	pelvic	ultrasound	would	be	indicated	to	rule	in	PCOS	if	diagnosis	cannot	be	made	based	on	the	presence	of	menstrual	irregularity	and	hyperandrogenism	(Fauser	et	al.	2012).	Transvaginal	ultrasound	provides	more	accurate	detection	of	the	presence	of	polycystic	ovaries,	but	should	not	be	performed	in	adolescents	who	have	not	yet	become	sexually	active;	in	this	case,	transabdominal	ultrasound	is	recommended	(Jean	Hailes	for	Women’s	Health,	2015).	Presenting	Complaint	Diagnosis	to	Consider	 Laboratory	test	 Expected	abnormal	result	if	condition	present	Normal	range*	(adult	female)	Amenorrhea/	 Pregnancy	 serum	beta-hCG	 >5	IU/L	 <5	IU/L	Oligomenorrhea	 Hyperthyroidism	 TSH	 <0.27	mU/L	 0.27-4.2mU/L			 		 (then	if	indicated,	free	T4)	 >20.0	mU/L	 10.5-20.0	mU/L			 Hyperprolactinemia	 Prolactin	 >25.0	ug/L	 	<25.0	ug/L			 Ovarian	insufficiency	 FSH	(would	be	in	post	menopausal	range)	 >	20.0	IU/L	 20.0-135	IU/L	Hirsutism	 Nonclassic	congenital	adrenal	hyperplasia	(NCCAH)	 follicular	phase	17	OHP	 >6	nmol/L	 0.3-4.0	nmol/L			 Cushing's	syndrome	 24	hour	urine	cortisol	 >	660	nmol/d	 30-220	nmol/d			 Adrenal	tumor	 dehydroepiandrosterone	sulfate	(DHEA-S)	 >13.6	umol/L	 <10.8	umol/L			 Androgen-secreting	tumor	 total	testosterone	 >5.2	nmol/L	 <1.8	nmol/L			 Ovarian	hyperthecosis		 total	testosterone	 >5.2	nmol/L	 <1.8	nmol/L	*Normal	ranges	obtained	from:	(Lifelabs	Clinical	Laboratories,	2015)	 		 			 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  41 Nurse	Practitioners	Nurse	Practitioners	are	registered	nurses	(RN)	who	have	nursing	experience	and	advanced	level	education	and	scope	of	practice.	Educational	philosophies	for	RNs	and	NPs	focus	on	a	holistic	approach	to	care,	taking	into	account	many	different	aspects	of	a	patients	physical	and	mental	health,	as	well	as	their	social	situation,	family,	and	quality	of	life	(CNA,	2014).	Responsibilities	of	the	NP	include	diagnosing	and	treating	illnesses,	prescribing	medications,	ordering	tests,	and	referring	to	specialists	based	upon	the	Scope	of	Practice	outlined	by	the	regulating	body	for	NPs:	the	College	of	Registered	Nurses	of	British	Columbia	(CRNBC)	(College	of	Registered	Nurses	of	British	Columbia,	2016).		The	level	of	education	required	in	each	province	differs	according	to	provincial	regulations	(MacDonald,	Schreiber,	&	Davis,	2005).	In	British	Columbia	(BC),	to	become	an	NP,	first	a	baccalaureate	RN	preparation	is	required,	followed	by	practical	experience	as	an	RN.	The	NP	education	is	a	combined	Masters	of	Nursing	and	NP	program,	followed	by	a	national	written	exam	and	a	provincially	regulated	practical	exam	(Spence,	Agnew,	&	Fahey-Walsh,	2015).	Scope	of	Practice	Nurse	practitioners	are	key	members	of	the	health	care	team	and	are	likely	to	see	women	presenting	with	signs	and	symptoms	of	PCOS	in	a	primary	care	setting.	NPs	need	to	be	able	to	recognize	all	the	possible	manifestations	and	clinical	presentations	that	are	possible	when	women	first	present	to	a	care	provider.	It	is	also	imperative	that	NPs	understand	the	scope	and	limitations	surrounding	their	role	in	PCOS,	the	necessary	workup	prior	to	referral,	and	appropriate	practitioners	to	collaborate	with	in	order	to	optimize	care	for	the	individual.		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  42 	 According	to	the	CRNBC	scope	of	practice	document	entitled	Applying	the	Competencies	Required	for	Nurse	Practitioners	in	British	Columbia	(2015),	PCOS	is	regarded	as	a	category	‘C’	diagnosis;	meaning	that	a	diagnosis	needs	to	be	made	in	collaboration	with	a	physician	or	specialist.	The	definition	of	this	category	‘C’	reads:	“The	nurse	practitioner	establishes	or	strongly	suspects	the	diagnosis	and	consults	with	a	physician	for	the	management	plan	or	consults	with	a	physician	to	confirm	the	diagnosis”	(College	of	Registered	Nurses	of	British	Columbia,	2015,	pg.	32).	This	referral	can	result	in	long	term	follow	up	and	management	by	the	specialist	physician	or	a	short	term,	one	time,	consultation	in	which	the	care	is	placed	back	in	the	hands	of	the	NP.	In	the	case	of	PCOS,	the	NP	will	be	referring	to	an	endocrinologist	and	potentially	other	specialist	such	as	a	cardiologist,	dermatologist,	or	fertility	specialist	for	collaborative	care.	In	BC,	NPs	have	certain	restriction	on	prescribing	authority	for	medications.	Some	of	these	include	the	medications	that	are	used	in	the	treatment	and	management	of	PCOS;	therefore,	collaboration	with	specialists	is	essential.			What	is	a	Guideline?		 A	clinical	practice	guideline	is	a	tool	for	practitioners	to	use	to	assist	them	in	making	appropriate	clinical	decisions	regarding	patient	diagnosis,	treatment,	screening,	health	promotion,	and	follow-up	or	referrals	(Brouwers,	et	al.,	2013).	They	are	usually	composed	by	a	team	of	experts	who	have	a	wide	breadth	of	clinical	knowledge	as	well	as	experience	in	research	and	clinical	trials.	The	combination	of	evidence-based	literature	with	the	clinical	expertise	of	the	authors	make	the	information	provided	in	guidelines	vital	to	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  43 optimizing	patient	care	by	the	primary	care	practitioner	(Misso,	Boyle,	Norman,	&	Teede,	2014).		 In	BC,	clinical	practice	guidelines	are	overseen	and	published	by	the	Guidelines	and	Protocols	Advisory	Committee	(GPAC)	which	is	a	collaborative	group	of	individuals	from	Doctors	of	BC	and	the	Ministry	of	Health	(BC	Guidelines,	nd).	GPAC	has	published	over	50	guidelines,	flow	sheets,	summaries,	and	tools	for	patient	education.		PCOS	Guideline		 The	clinical	practice	guideline	that	will	accompany	this	literature	review	was	developed	for	the	successful	completion	of	NURS	596	Culminating	Project	for	the	Masters	of	Nursing/Nurse	Practitioner	program	at	the	University	of	British	Columbia.	It	was	developed	for	use	by	NPs	in	BC	in	order	to	outline	the	diagnostic	criteria	of	PCOS	and	assist	in	understanding	the	diagnostic	workup	and	long-term	management	of	adult	women	with	PCOS.	It	is	intended	for	use	in	a	clinical	practice	setting	when	working	with	adult	women	presenting	to	their	primary	care	NP	with	symptoms	such	as	amenorrhea,	hirsutism,	or	infertility.	It	provides	NPs	with	guidance	to	make	decisions	regarding	the	care	and	work-up	for	women	with	PCOS.	It	focuses	on	appropriate	diagnostic	workup,	timing	for	referrals,	and	the	long-term	screening	and	management	necessary	to	optimize	the	care	of	women	after	their	diagnosis	of	PCOS.	Upon	completion,	this	guideline	will	be	submitted	to	GPAC	for	potential	implementation	into	the	BC	Guidelines	for	use	by	all	primary	care	providers.			Discussion		 PCOS	is	a	complex,	multifaceted	syndrome	with	multiple	health	implications	and	long-term	health	risks	(Fauser	et	al.,	2012).	Women	with	PCOS	require	management	and	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  44 guidance	from	their	primary	care	NP	as	well	as	multiple	specialists.	Due	to	the	heterogeneity	of	the	syndrome,	diagnosis,	symptomatic	treatment,	and	long	term	management	is	very	complex	and	individualized	(Fauser	et	al.,	2012).	Long-term	complications	of	PCOS	include	increased	risk	for	IR,	CVD,	endometrial	cancer,	obesity,	depression	and	anxiety,	infertility,	and	various	dermatological	manifestations	(Fauser	et	al.,	2012).		 	Diagnosis	of	PCOS	is	complicated	by	various	different	diagnostic	criteria.	Research	for	this	literature	review	reveals	that	the	most	widely	accepted	diagnostic	criteria	to	date	is	the	Rotterdam	criteria,	which	was	developed	in	2003.	These	criteria	encompass	a	broader	expression	of	the	syndrome	and	require	two	of	the	following	three	criteria:	oligo-	and/or	anovulation,	clinical	and/or	biochemical	hyperandrogenism,	or	polycystic	ovaries	(Rotterdam,	2004).	It	is	outside	the	scope	of	practice	for	NPs	in	BC	to	diagnose	PCOS,	however,	NPs	are	highly	involved	in	the	co-management	with	various	specialists	and	play	a	vital	role	in	the	health	of	women	with	PCOS.		Implications	for	Practice			 The	purpose	of	this	literature	review	was	to	find	supporting	evidence	to	create	a	clinical	practice	guideline	for	use	by	the	NP	in	BC.	Throughout	the	development	of	this	literature	review,	many	other	guidelines	and	review	articles	were	evaluated	and	a	Nurse	Practitioner	Clinical	Practice	Guideline	was	developed	based	on	the	evidence.	This	guideline	is	shown	in	Appendix	C	and	is	specific	to	adult	patients	with	PCOS	and	has	incorporated	BC	Guidelines	as	well	as	PCOS	specific	guidelines	from	other	countries.	This	literature	review	and	clinical	practice	guideline	will	support	NPs	in	the	evaluation	and	management	of	adult	women	with	PCOS.	It	also	assists	NPs	in	confidently	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  45 assessing	women	presenting	with	the	various	clinical	manifestations	of	PCOS	and	allow	them	to	rule	in	and	rule	out	other	causes	of	the	symptoms.	Further	Research	and	Projects		 Despite	the	comprehensive	nature	of	this	literature	review	and	clinical	practice	guideline	it	is	solely	developed	for	management	of	the	adult	women	with	PCOS.	Future	research	and	guideline	development	could	be	directed	towards	the	care	and	management	of	women	with	PCOS	in	special	populations	such	as	adolescents	or	postmenopausal	women.	It	could	also	cover	special	considerations	in	the	health	of	the	woman	with	PCOS	during	pregnancy.		Conclusion	Polycystic	ovary	syndrome	is	a	complex	disease	with	varying	clinical	presentations,	diagnostic	criteria,	and	long-term	metabolic	and	cardiovascular	complications	(Fauser	et	al.,	2012).	The	complexity	of	symptoms	and	complications	of	PCOS	require	involvement	of	various	different	specialists;	however,	the	primary	care	provider,	such	as	the	NP,	is	involved	in	the	overall	long-term	management.		This	literature	review	evaluates	the	current	literature	recommendations	regarding	diagnosis,	workup,	and	management	of	women	with	PCOS.	It	also	highlights	the	disorders	that	can	possibly	mimic	PCOS	and	provides	the	resources	necessary	for	the	NP	to	rule	out	these	disorders	and	narrow	down	a	diagnosis	of	PCOS.	Due	to	the	advanced	level	of	education	and	scope	of	practice	of	the	NP,	they	are	in	a	unique	position	to	provide	care	to	women	with	PCOS.	With	the	assistance	of	the	information	presented	in	this	literature	review	and	accompanying	primary	care	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  46 guideline,	the	NP	will	have	the	tools	necessary	provide	comprehensive,	holistic	care	to	women	with	PCOS.		 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  47 References	Andreeff,	R.	(2014).	Amenorrhea.	Journal	of	the	American	Academy	of	Physician	Assistants,	27(10),	50-51.	doi:10.1097/01.JAA.0000453871.15689.a2		Azziz,	R.,	Carmina,	E.,	Dewailly,	D.,	Diamanti-Kandarakis,	E.,	Escobar-Morreale,	H.	F.,	Futterweit,	W.,…	Witchel	S.	F.	(2006).	Position	statement:	Criteria	for	defining	polycystic	ovary	syndrome	as	a	predominantly	hyperandrogenic	syndrome:	An	Androgen	Excess	Society	guideline.	The	Journal	of	Clinical	Endocrinology	and	Metabolism,	91(11),	4237.		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Obstetrical	&	Gynecological	Survey,	66(5),	285-287.	doi:10.1097/OGX.0b013e318227fc94	 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  58 Appendix	A	Patient	Health	Questionnaire	(PHQ-9)		Patient	name:	__________________________________	Date:	___________________		1.	Over	the	last	2	weeks,	how	often	have	you	been	bothered	by	any	of	the	following	problems?			 Not	at	all	(0)		Several	days	(1)		 More	than	half	the	days	(2)		 Nearly	every	day	(3)		a.	Little	interest	or	pleasure	in	doing	things.		☐	 ☐	 ☐	 ☐	b.	Feeling	down,	depressed,	or	hopeless.		 ☐		 ☐	 ☐		 ☐	c.	Trouble	falling/staying	asleep,	sleeping	too	much.		 ☐	 ☐	 ☐	 ☐	d.	Feeling	tired	or	having	little	energy.		 ☐	 ☐	 ☐	 ☐	e.	Poor	appetite	or	overeating.		 ☐		 ☐	 ☐	 ☐	f.	Feeling	bad	about	yourself,	or	that	you	are	a	failure,	or	have	let	yourself	or	your	family	down.		 ☐	 ☐	 ☐	 ☐	g.	Trouble	concentrating	on	things,	such	as	reading	the	newspaper	or	watching	TV.		 ☐	 ☐	 ☐	 ☐	h.	Moving	or	speaking	so	slowly	that	other	people	could	have	noticed.	Or	the	opposite;	being	so	fidgety	or	restless	that	you	have	been	moving	around	more	than	usual.		 ☐	 ☐	 ☐	 ☐	i.	Thoughts	that	you	would	be	better	off	dead	or	of	hurting	yourself	in	some	way.		 ☐	 ☐	 ☐	 ☐	2.	If	you	checked	off	any	problem	on	this	questionnaire	so	far,	how	difficult	have	these	problems	made	it	for	you	to	do	your	work,	take	care	of	things	at	home,	or	get	along	with	other	people?		☐	Not	difficult	at	all		☐	Somewhat	difficult		☐	Very	difficult		☐	Extremely	difficult		TOTAL	SCORE	_________________				 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  59 Instructions	–	How	to	Score	the	PHQ-9	Major	depressive	disorder	is	suggested	if:		• Of	the	9	items,	5	or	more	are	checked	as	at	least	‘more	than	half	the	days’		• Either	item	a.	or	b.	is	positive,	that	is,	at	least	‘more	than	half	the	days’		Other	depressive	syndrome	is	suggested	if:		• Of	the	9	items,	a.,	b.	or	c.	is	checked	as	at	least	‘more	than	half	the	days’		• Either	item	a.	or	b.	is	positive,	that	is,	at	least	‘more	than	half	the	days’		Also,	PHQ-9	scores	can	be	used	to	plan	and	monitor	treatment.	To	score	the	instrument,	tally	each	response	by	the	number	value	under	the	answer	headings,	(not	at	all=0,	several	days=1,	more	than	half	the	days=2,	and	nearly	every	day=3).	Add	the	numbers	together	to	total	the	score	on	the	bottom	of	the	questionnaire.	Interpret	the	score	by	using	the	guide	listed	below.		Guide	for	Interpreting	PHQ-9	Scores		Score		 Recommended	Actions		0-4		 Normal	range	or	full	remission.	The	score	suggests	the	patient	may	not	need	depression	treatment.		5-9		 Minimal	depressive	symptoms.	Support,	educate,	call	if	worse,	return	in	1	month.		10-14		 Major	depression,	mild	severity.	Use	clinical	judgment	about	treatment,	based	on	patient’s	duration	of	symptoms	and	functional	impairment.	Treat	with	antidepressant	or	psychotherapy.		15-19		 Major	depression,	moderate	severity.	Warrants	treatment	for	depression,	using	antidepressant,	psychotherapy	or	a	combination	of	treatment.		20	or	higher		 Major	depression,	severe	severity.	Warrants	treatment	with	antidepressant	and	psychotherapy,	especially	if	not	improved	on	monotherapy;	follow	frequently.				(UBC	Mood,	n.d.)			 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  60 Appendix	B	Generalized	Anxiety	Disorder	(GAD-7)	GAD-7	stands	for	"generalized	anxiety	disorder"	and	the	7	questions	in	the	tool.	Choose	one	answer	for	each	of	the	7	questions	below:		Over	the	last	2	weeks,	how	often	have	you	been	bothered	by	the	following	problems?		 Not	at	all		Several	days		 More	than	half	the	days		Nearly	every	day		1.	Feeling	nervous,	anxious	or	on	edge		 0		 1		 2		 3		2.	Not	being	able	to	stop	or	control	worrying		 0		 1		 2		 3		3.	Worrying	too	much	about	different	things		 0		 1		 2		 3		4.	Trouble	relaxing		 0		 1		 2		 3		5.	Being	so	restless	that	it's	hard	to	sit	still		 0		 1		 2		 3		6.	Becoming	easily	annoyed	or	irritable		 0		 1		 2		 3		7.	Feeling	afraid,	as	if	something	awful	might	happen		 0		 1		 2		 3		Add	up	your	results	for	each	column		 	 	 	 	Total	score	(add	column	totals	together)		 	What	your	total	score	means		• Your	total	score	is	a	guide	to	how	severe	your	anxiety	disorder	may	be:		• 0	to	4	=	mild	anxiety		• 5	to	9	=	moderate	anxiety		• 10	to	14	=	moderately	severe	anxiety		• 15	to	21	=	severe	anxiety		If	your	score	is	10	or	higher,	or	if	you	feel	that	anxiety	is	affecting	your	daily	life,	call	your	doctor.		(Healthlink	BC,	2015)			 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  61 Appendix	C	British	Columbia	Nurse	Practitioner	Guidelines		Polycystic	Ovary	Syndrome:	Diagnosis	and	Management	in	the	Adult	Patient		Effective	Date:	April	2016		Scope_________________________________________________________________________		This	guideline	provides	recommendations	for	the	primary	care	Nurse	Practitioner	to	assist	in	diagnosis	and	long-term	management	of	Polycystic	Ovary	Syndrome	(PCOS)	in	adult	women	≥	19	years	of	age.			Key	Recommendations___________________________________________________________	• PCOS	is	a	multifaceted	disease	with	multiple	long-term	cardiovascular	and	metabolic	risk	factors.	Management	guidelines	focus	on	decreasing	risk	factors	and	screening	for	presence	of	associated	comorbidities.	• Diagnosis	of	PCOS	is	based	on	the	Rotterdam	criteria.		• Multidisciplinary	management	between	specialists	and	the	primary	care	NP	will	optimize	care	of	women	with	PCOS.	• Women	with	PCOS	should	be	encouraged	to	see	their	primary	care	provider	every	2	years	or	every	1	year	if	at	high	risk	for	cardiovascular	or	metabolic	disease		Definition_____________________________________________________________________	Polycystic	ovary	syndrome	is	a	multifaceted	disease	with	a	wide	range	of	clinical	presentations,	various	different	diagnostic	criteria,	and	multiple	long-term	metabolic	and	cardiovascular	complications	(Fauser	et	al.,	2012).		Pathophysiology________________________________________________________________	The	cause	of	PCOS	is	complex	and	multifactorial	and	even	after	much	investigation	into	the	pathogenesis,	the	cause	is	still	relatively	unclear.	In	addition	to	the	numerous	genes	that	are	identified	to	be	correlated	with	PCOS,	there	is	growing	evidence	to	suggest	that	particular	environmental	factors	such	as	low	socio-economic	status,	smoking,	poor	diet,	and	lack	of	exercise	also	contribute	to	the	development	of	the	syndrome	(Barthelmess	&	Naz,	2015).		Detection______________________________________________________________________	Clinical	investigations	for	the	presence	of	polycystic	ovary	syndrome	would	begin	after	a	patient	presents	with	symptoms	such	as	clinical	hyperandrogenism,	oligomenorrhea	or	amenorrhea,	or	infertility.					 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  62 Diagnosis______________________________________________________________________	Polycystic	ovary	syndrome	is	usually	detected	during	the	early	reproductive	years	due	to	presenting	complaints	such	as	menstrual	irregularity,	clinical	hyperandrogenism,	or	infertility	(Fauser	et	al.,	2012).	It	is	not	within	the	NP	scope	in	BC	to	diagnose	PCOS,	however,	NPs	can	assist	in	the	initial	diagnostic	workup	to	help	rule	in,	or	rule	out	other	causes	of	the	presenting	complaint.			Diagnosis	is	based	on	the	Rotterdam	criteria:	Patient	must	have	2	of	the	3	following	(and	exclusion	of	other	etiologies):	1. Oligo-ovulation	or	chronic	anovulation	2. Clinical	and/or	biochemical	signs	of	hyperandrogenism	3. Polycystic	ovaries		Initial	Diagnostic	Workup_______________________________________________________	Ruling	out	other	etiologies	that	could	be	producing	PCOS-like	symptoms,	is	essential	prior	to	diagnosis	of	PCOS.	Table	2	outlines	other	etiologies	and	diagnostic	workup	to	rule	in	or	rule	out	these	potential	diagnoses.		In	addition	to	the	laboratory	tests	in	Table	2,	a	pelvic	ultrasound	would	be	indicated	to	rule	in	PCOS	if	diagnosis	cannot	be	made	based	on	the	presence	of	menstrual	irregularity	and	hyperandrogenism	(Fauser	et	al.	2012).		• Transvaginal	ultrasound	is	preferred		• Transabdominal	ultrasound	is	recommended	for	adolescents	who	have	not	yet	become	sexually	active			Table	1	 		 		 		 		Presenting	Complaint	Diagnosis	to	Consider	 Laboratory	test	 Expected	abnormal	result	if	condition	present	Normal	range*	(adult	female)	Amenorrhea/	 Pregnancy	 serum	beta-hCG	 >5	IU/L	 <5	IU/L	Oligomenorrhea	 Hyperthyroidism	 TSH	 <0.27	mU/L	 0.27-4.2mU/L			 		 (then	if	indicated,	free	T4)	 >20.0	mU/L	 10.5-20.0	mU/L			 Hyperprolactinemia	 Prolactin	 >25.0	ug/L	 	<25.0	ug/L			Ovarian	insufficiency	 FSH	(would	be	in	post	menopausal	range)	>	20.0	IU/L	 20.0-135	IU/L	Hirsutism	 Nonclassic	congenital	adrenal	hyperplasia	(NCCAH)	follicular	phase	17	OHP	 >6	nmol/L	 0.3-4.0	nmol/L			 Cushing's	syndrome	 24	hour	urine	cortisol	 >	660	nmol/d	 30-220	nmol/d			Adrenal	tumor	 dehydroepiandrosterone	sulfate	(DHEA-S)	>13.6	umol/L	 <10.8	umol/L			 Androgen-secreting	tumor	 total	testosterone	 >5.2	nmol/L	 <1.8	nmol/L			 Ovarian	hyperthecosis		 total	testosterone	 >5.2	nmol/L	 <1.8	nmol/L	*Normal	ranges	obtained	from:	(Lifelabs	Clinical	Laboratories,	2015)	 		 		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  63 Management	Guidelines	for	Initial	Workup	and	Long-Term	Screening____________________		Metabolic	Risk:	PCOS	is	associated	with	increase	risk	for	insulin	resistance,	metabolic	syndrome,	and	Type	2	diabetes	mellitus.	5. Screening	for	IR	with	a	2-hr	75g	OGTT	is	recommended	in	women	with	PCOS	at	onset	of	diagnosis	and	every	two	years	thereafter.	6. Screening	with	a	2-hr	75g	OGTT	should	be	performed	every	year	if	the	patient	possesses	the	following	risk	factors	(Ekoé,	Punthakee,	Ransom,	Prebtani,	&	Goldenberg,	2013;	Jean	Hailes	for	Women’s	Health,	2015):	• PCOS	presentation:	hyperandrogenism	with	anovulation		• Acanthosis	nigricans	• Obesity	(BMI>	25	kg/m2)	• Ethnicity:	Aboriginal,	Hispanic,	South	Asian,	Asian,	or	African	descent	• Parental	history	of	diabetes	• History	of	high	blood	glucose	levels	• Physical	inactivity	7. Initial	treatment	of	elevated	blood	sugar	levels:	metformin	250-500mg	PO	BID	(BC	Guidelines,	2015b).		8. If	not	being	followed	by	endocrinology	already,	the	patient	should	be	referred	to	endocrinology	at	onset	of	diagnosis	of	diabetes.			Cardiovascular	Disease	Risk:	PCOS	is	associated	with	higher	cardiovascular	disease	risk	7. Screening	for	CVD	should	be	performed	every	2	years	(Jean	Hailes	for	Women’s	Health,	2015).	8. If	risk	factors	present,	screening	should	be	performed	every	1	year	(Jean	Hailes	for	Women’s	Health,	2015).	9. Screening	includes	monitoring	for	the	presence	of	CVD	risk	factors	and	entails	assessing:	• Waist	circumference:	target	<88cm	(Goldenberg	&	Punthakee,	2013)	• BMI:	target	<25	kg/m2	(BC	Guidelines,	2014)	• Smoking	status:	goal	is	reduction	or	quitting	smoking	(BC	Guidelines,	2014)	• Exercise	habits:	goal	is	30	min	of	moderate	to	vigorous	activity	5-7	days	a	week	(BC	Guidelines,	2014)	• Blood	pressure:	target	<140/90	or	<130/90	if	diabetic	(BC	Guidelines,	2015a)	• Lipid	profiles:	aim	is	LDL	<3.5	(BC	Guidelines,	2014)	• OGTT:	target	<11.0	(Ekoé,	et	al.,	2013)	10. Women	with	high	blood	pressure	or	hyperlipidemia	should	be	treated	appropriately	by	the	NP	according	to	BC	Guideline	recommendations.	11. Counselling	for	smoking	cessation	strategies	should	be	provided	for	women	who	smoke.	Resources	to	offer	include	www.quitnow.ca	(BC	Guidelines,	2014).	12. Referral	to	a	cardiologist	should	be	considered	to	optimize	patient	care	(Jean	Hailes	for	Women’s	Health,	2015).		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  64 Endometrial	Cancer	Risk:	Management	goals	are	based	upon	reducing	risk	factors	and	preventing	the	development	of	endometrial	cancer.	5. Women	with	PCOS	should	have	a	menstrual	bleed	at	least	4	times	every	year	(Chittenden,	2009).	6. First	line	treatment	for	amenorrhea	in	order	to	reduce	the	risk	of	endometrial	cancer	includes	lifestyle	management	such	as	diet	and	exercise	with	goal	weight	loss	of	5-10%	body	weight	(Klein,	2013).	7. Pharmacologic	treatments	include	initiation	of	low-dose	combination	oral	contraceptives	to	regulate	hormone	levels	(Jean	Hailes	for	Women’s	Health,	2015).	8. Referral	to	gynecology	should	be	considered	in	women	with	persistent	oligomenorrhea	or	amenorrhea	who	are	not	menstruating	at	least	4	times	per	year.		Obesity:	Severity	of	PCOS	symptoms	is	strongly	correlated	with	increasing	levels	of	obesity.	Higher	rates	of	obesity	are	seen	in	women	with	PCOS	compared	to	control	groups.		9. Weight,	height,	BMI	calculation,	and	waist	circumference	should	be	obtained	at	each	annual	or	biennial	visit.		10. Target	waste	circumference	is	<88cm	and	target	BMI	is	<25	kg/m2,	see	Table	2	(BC	Guidelines,	2011).	11. In	the	overweight	or	obese	population,	the	NP	should	provide	adequate	diet	and	exercise	counselling	regarding	lifestyle	measures	to	reduce	obesity	and	increase	exercise	habits.	The	NP	should	stress	that	even	a	5%	reduction	in	weight	assists	in	return	of	menstruation	and	an	improvement	of	symptoms	of	hyperandrogenemia.		12. Obesity	class	1:	Lifestyle	management	is	recommended		13. Obesity	class	2	or	3,	or	women	with	comorbidities	such	as	type	2	diabetes,	hypertension,	CVD,	osteoarthritis,	dyslipidemia,	and	sleep	apnea:	more	intensive	interventions	such	as	lifestyle	management	in	combination	with	pharmacologic	or	surgical	interventions	is	recommended.		14. Strategies	for	non-pharmacologic	weight	reduction	include:	a. Caloric	restriction	of	500-1000kcal/day	b. Physical	activity:	30+	minutes	of	moderate	to	vigorous	physical	activity	5-7	times	per	week	c. No	more	than	0.5-1kg/week	weight	loss	d. Establishing	initial	weight	loss	goal	of	5-10%	of	body	weight	e. Referral	to	weight	loss	program	and	support	groups	15. Pharmacologic	therapy	for	obesity	class	2	and	3	after	diet,	exercise,	and	behavioural	programs	have	failed:	orlistat	(Xenical)		16. Referral	to	surgeon	for	gastric	bypass	surgery	if	unable	to	obtain	or	maintain	weight	reduction	strategies							 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  65 Table	2:	BMI	Ranges	 		Weight	Classification	 BMI	(kg/m2)	Underweight	 <18.5	Normal	 18.5-24.9	Overweight	 25-29.9	Obese:	Class	1	 30-34.9	Obese:	Class	2	 35-39.9	Obese:	Class	3	 ≥	40			(adapted	from	BC	Guidelines,	2011)		Mental	Health:	Women	with	PCOS	experience	higher	rates	of	anxiety,	depression,	and	emotional	distress	compared	to	control	groups.		5. NPs	should	have	discussions	with	their	patients	regarding	moods	and	quality	of	life	and	screen	for	the	presence	of	emotional	distress	with	every	annual	or	biennial	visit.	6. Women	with	PCOS	should	be	screened	for	emotional	distress	with	the	following	two	questions	(BC	Guidelines,	2013):	In	the	past	month:		III. Have	you	lost	interest	or	pleasure	in	things	you	usually	like	to	do?	IV. Have	you	felt	sad,	low,	down,	depressed	or	hopeless?		7. If	a	woman	answers	yes	to	either	question,	further	screening	is	recommended	with	the	PHQ-9	(Appendix	A)	or	the	GAD-7	questionnaire	(Appendix	B).		8. NPs	should	refer	to	the	BC	Guideline	for	full	management	guidelines:	http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/depression_full_guideline.pdf		Infertility:	Many	women	with	POCS	experience	infertility;	however,	infertility	rates	decrease	with	weight	loss	and	lifestyle	management.	5. Lifestyle	management	for	weight	loss	is	first	line	treatment	for	infertility	in	obese	women	with	PCOS	and	should	be	trialed	for	3-6	months	prior	to	discussions	and	interventions	for	ovulation	induction	(Jean	Hailes	for	Women’s	Health,	2015).	6. Counselling	should	include	discussion	regarding	avoiding	factors	that	may	contribute	to	infertility	such	as:	smoking,	excessive	alcohol	use,	and	ensuring	the	couple	is	engaging	in	intercourse	at	least	every	1-2	days	around	the	time	of	ovulation.		7. Diagnostic	laboratory	workup	for	infertility	by	the	NP	includes:	FSH,	LH,	progesterone,	estradiol,	prolactin,	and	TSH	(Lindsay	&	Vitrikas,	2015).	8. Referral	to	an	infertility	specialist	should	occur	after	lifestyle	interventions	for	weight	loss	have	been	attempted	for	3-6	months	and	pregnancy	has	not	been	successful	(Jean	Hailes	for	Women’s	Health,	2015).		Dermatology:	PCOS	is	associated	with	multiple	dermatological	manifestations	including	hirsutism,	acne,	and	alopecia.		5. Interventions	for	clinical	hyperandrogenemia	focus	on	reducing	steroid	production	from	the	ovaries,	thus	reducing	bioavailabity.		 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  66 6. Oral	contraceptive	pills	are	commonly	used	for	clinical	hyperandrognemism,	either	alone,	or	in	combination	with	an	antiandrogen	such	as	spironolactone	(Fauser	et	al.,	2012).	7. Laser	therapy	is	an	effective	measure	for	elimination	of	unwanted	body	hair	but	is	expensive	and	time-consuming.	It	can	be	recommended	to	patients	if	cost	is	not	a	factor	(Bode,	Seehusen,	&	Baird,	2012).	8. Acne	management	includes	assessment	and	determination	of	type	and	severity	of	acne.	First	line	treatment	options	include	combination	estrogen	and	progesterone	oral	contraceptive	pills,	or	topical	retinoid,	either	alone,	or	in	combination	with	a	topical	antibiotic	(Titus	&	Hodge,	2012).				 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  67 References_____________________________________________________________________			Azziz,	R.,	Carmina,	E.,	Dewailly,	D.,	Diamanti-Kandarakis,	E.,	Escobar-Morreale,	H.	F.,	Futterweit,	W.,…	Witchel	S.	F.	(2009).	The	Androgen	Excess	and	PCOS	Society	criteria	for	the	polycystic	ovary	syndrome:	The	complete	task	force	report.	Fertility	and	Sterility,	91(2),	456-488.	doi:10.1016/j.fertnstert.2008.06.035		Barber,	T.	M.,	McCarthy,	M.	I.,	Wass,	J.	A.	H.,	&	Franks,	S.	(2006).	Obesity	and	polycystic	ovary	syndrome.	Clinical	Endocrinology,	65(2),	137-145.	doi:10.1111/j.1365-2265.2006.02587.x		Barthelmess,	E.	K.	&	Naz,	R.	K.	(2015).	Polycystic	ovary	syndrome:	Current	status	and	future	perspectives.	Front	Biosci	(Elite	Ed.)	6,	104-119.		BC	Guidelines	(2011).	Overweight	and	obese	adults:	Diagnosis	and	Management.	BC	Guidelines.	Retrieved	on	Feb.	19th,	2016,	from:	http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/obesity.pdf		BC	Guidelines	(2014).	Cardiovascular	disease:	Primary	prevention.	BC	Guidelines.	Retrieved	Feb.	19th,	2016.	http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/cvd.pdf		BC	Guidelines	(2015a).	Hypertension:	Diagnosis	and	management.	BC	Guidelines.	Retrieved	Feb.	19th,	2016	from:	http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/htn-full-guideline.pdf		BC	Guidelines	(2015b).	Diabetes	care.	BC	Guidelines.	Retrieved	March	13th,	2016	from	http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/diabetes_care_full_guideline.pdf		Bode,	D.,	Seehusen,	D.	A.,	&	Baird,	D.	(2012).	Hirsutism	in	women.	American	Family	Physician	85(4),	373-380.	Ekoé,	J.,	Punthakee,	Z.,	Ransom,	T.,	Prebtani,	A.	P.	H.,	&	Goldenberg,	R.	(2013).	Screening	for	type	1	and	type	2	diabetes.	Canadian	Journal	of	Diabetes,	37,	S12-S15.	doi:http://dx.doi.org/10.1016/j.jcjd.2013.01.012	Fauser,	B.	C.	J.	M.,	Tarlatzis,	B.	C.,	Rebar,	R.	W.,	Legro,	R.	S.,	Balen,	A.	H.,	Lobo,	R.,…	Barnhart,	K.	(2012).	Consensus	on	women's	health	aspects	of	polycystic	ovary	syndrome	(PCOS):	The	Amsterdam	ESHRE/ASRM-sponsored	3rd	PCOS	consensus	workshop	group.	Fertility	and	Sterility,	97(1),	28-38.	doi:10.1016/j.fertnstert.2011.09.024		Goldenberg,	R.,	&	Punthakee,	Z.	(2013).	Definition,	classification	and	diagnosis	of	diabetes,	prediabetes	and	metabolic	syndrome.	Canadian	Journal	of	Diabetes	37,	S8-S11.	doi:http://dx.doi.org/10.1016/j.jcjd.2013.01.011			 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  68 Healthlink	BC	(2015).	Selftest	for	Anxiety.		Retrieved	on	Feb.	18th,	2016,	from:	http://www.healthlinkbc.ca/healthwise/includes/media/pdf/hw/form_abn2339.pdf?lang=en-ca	Jean	Hailes	for	Women’s	Health	(2015).	Evidence-based	guideline	for	the	assessment	and	management	of	polycystic	ovary	syndrome.	PCOS	Australian	Alliance,	Melbourne.	Retrieved	on	May	30th,	2015	from:	https://jeanhailes.org.au/contents/documents/Resources/Tools/PCOS_evidence-based_guideline_for_assessment_and_management_pcos.pdf		Klein,	D.	A.	&	Poth,	M.	A.	(2013).	Amenorrhea:	An	approach	to	diagnosis	and	management.	American	Family	Physician	87(11),	781-788.		Lifelabs	Clinical	Laboratories	(2015).	Reference	intervals.	Burnaby	Reference	Laboratory:	Burnaby,	British	Columbia.			Lindsay,	T.	J.	&	Vitrikas	K.	R.	(2015),	Evaluation	and	treatment	of	infertility.	American	Family	Physician	91(5),	308-314			Titus,	S.	&	Hodge,	J.	(2012).	Diagnosis	and	treatment	of	acne.	American	Family	Physician	86(8),	734-740.		UBCmood.ca	(n.d).		Patient	health	questionnaire	(PHQ-9).	Retrieved	on	Feb.	18th,	2016	from	http://www.ubcmood.ca/sad/PHQ-9.pdf				 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  69 Appendix	A____________________________________________________________________	Patient	Health	Questionnaire	(PHQ-9)		Patient	name:	__________________________________	Date:	___________________		1.	Over	the	last	2	weeks,	how	often	have	you	been	bothered	by	any	of	the	following	problems?			Not	at	all	(0)		Several	days	(1)		More	than	half	the	days	(2)		Nearly	every	day	(3)		a.	Little	interest	or	pleasure	in	doing	things.		 ☐	 ☐	 ☐	 ☐	b.	Feeling	down,	depressed,	or	hopeless.		 ☐		 ☐	 ☐		 ☐	c.	Trouble	falling/staying	asleep,	sleeping	too	much.		☐	 ☐	 ☐	 ☐	d.	Feeling	tired	or	having	little	energy.		 ☐	 ☐	 ☐	 ☐	e.	Poor	appetite	or	overeating.		 ☐		 ☐	 ☐	 ☐	f.	Feeling	bad	about	yourself,	or	that	you	are	a	failure,	or	have	let	yourself	or	your	family	down.		☐	 ☐	 ☐	 ☐	g.	Trouble	concentrating	on	things,	such	as	reading	the	newspaper	or	watching	TV.		☐	 ☐	 ☐	 ☐	h.	Moving	or	speaking	so	slowly	that	other	people	could	have	noticed.	Or	the	opposite;	being	so	fidgety	or	restless	that	you	have	been	moving	around	more	than	usual.		☐	 ☐	 ☐	 ☐	i.	Thoughts	that	you	would	be	better	off	dead	or	of	hurting	yourself	in	some	way.		☐	 ☐	 ☐	 ☐	2.	If	you	checked	off	any	problem	on	this	questionnaire	so	far,	how	difficult	have	these	problems	made	it	for	you	to	do	your	work,	take	care	of	things	at	home,	or	get	along	with	other	people?		☐	Not	difficult	at	all		☐	Somewhat	difficult		☐	Very	difficult		☐	Extremely	difficult		TOTAL	SCORE	_________________						 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  70 Instructions	–	How	to	Score	the	PHQ-9	Major	depressive	disorder	is	suggested	if:		• Of	the	9	items,	5	or	more	are	checked	as	at	least	‘more	than	half	the	days’		• Either	item	a.	or	b.	is	positive,	that	is,	at	least	‘more	than	half	the	days’		Other	depressive	syndrome	is	suggested	if:		• Of	the	9	items,	a.,	b.	or	c.	is	checked	as	at	least	‘more	than	half	the	days’		• Either	item	a.	or	b.	is	positive,	that	is,	at	least	‘more	than	half	the	days’		Also,	PHQ-9	scores	can	be	used	to	plan	and	monitor	treatment.	To	score	the	instrument,	tally	each	response	by	the	number	value	under	the	answer	headings,	(not	at	all=0,	several	days=1,	more	than	half	the	days=2,	and	nearly	every	day=3).	Add	the	numbers	together	to	total	the	score	on	the	bottom	of	the	questionnaire.	Interpret	the	score	by	using	the	guide	listed	below.		Guide	for	Interpreting	PHQ-9	Scores		Score		 Recommended	Actions		0-4		 Normal	range	or	full	remission.	The	score	suggests	the	patient	may	not	need	depression	treatment.		5-9		 Minimal	depressive	symptoms.	Support,	educate,	call	if	worse,	return	in	1	month.		10-14		Major	depression,	mild	severity.	Use	clinical	judgment	about	treatment,	based	on	patient’s	duration	of	symptoms	and	functional	impairment.	Treat	with	antidepressant	or	psychotherapy.		15-19		 Major	depression,	moderate	severity.	Warrants	treatment	for	depression,	using	antidepressant,	psychotherapy	or	a	combination	of	treatment.		20	or	higher		Major	depression,	severe	severity.	Warrants	treatment	with	antidepressant	and	psychotherapy,	especially	if	not	improved	on	monotherapy;	follow	frequently.				(UBC	Mood,	n.d.)		 	 POLYCYSTIC OVARY SYNDROME IN ADULTS                                                                  71 Appendix	B____________________________________________________________________	Generalized	Anxiety	Disorder	(GAD-7)	GAD-7	stands	for	"generalized	anxiety	disorder"	and	the	7	questions	in	the	tool.	Choose	one	answer	for	each	of	the	7	questions	below:		Over	the	last	2	weeks,	how	often	have	you	been	bothered	by	the	following	problems?		Not	at	all		Several	days		More	than	half	the	days		Nearly	every	day		1.	Feeling	nervous,	anxious	or	on	edge		 0		 1		 2		 3		2.	Not	being	able	to	stop	or	control	worrying		 0		 1		 2		 3		3.	Worrying	too	much	about	different	things		 0		 1		 2		 3		4.	Trouble	relaxing		 0		 1		 2		 3		5.	Being	so	restless	that	it's	hard	to	sit	still		 0		 1		 2		 3		6.	Becoming	easily	annoyed	or	irritable		 0		 1		 2		 3		7.	Feeling	afraid,	as	if	something	awful	might	happen		 0		 1		 2		 3		Add	up	your	results	for	each	column		 	 	 	 	Total	score	(add	column	totals	together)		 	What	your	total	score	means		• Your	total	score	is	a	guide	to	how	severe	your	anxiety	disorder	may	be:		• 0	to	4	=	mild	anxiety		• 5	to	9	=	moderate	anxiety		• 10	to	14	=	moderately	severe	anxiety		• 15	to	21	=	severe	anxiety		If	your	score	is	10	or	higher,	or	if	you	feel	that	anxiety	is	affecting	your	daily	life,	call	your	doctor.		(Healthlink	BC,	2015)		

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