pcos update 2019: common, subtle, and more serious than ever · diagnosis of pcos • clinical...

PCOS Update 2019:

Common, Subtle, and More

Serious Than Ever

R. Mimi Secor, DNP, FNP-BC, FAANP

Onset, Massachusetts

Mimi Secor, DNP, FNP-BC, FAANP• FNP for 41 years specializing in Women’s Health

• National Speaker, Educator, Author, Entrepreneur, Athlete

• 2013 Lifetime Achievement Award, (Mass Coalition of NPs)

• DNP-2015, Rocky Mountain University, Provo, Utah

• Also graduated w/ 30 lb weight loss, 12 inches off waist

• 2016 First Bodybuilding Competition, 5th Place trophy

• 2018 (July 28) Fourth Competition, 2nd Place in over 55 !!!

• #1 International Best-Selling Author of NEW Book,

• “Debut a New You: Transforming Your Life at Any Age"

• Passion for Helping NPs/PAs become Healthy and Fit

Secor 2019 copyright


Mimi Secor, DNP, FNP-BC, FAANP

Disclosure

Consultant:

• Hologic, Medical Devices, ThinPrep,

Mammograms, Novasure for AUB

Speaker:

• Duchesney, Osphena for VVA

PCOS Objectives for Session

Upon completion of this session attendees will be able to:

• Discuss epidemiology, pathophysiology,

associated risks and complications

15 minutes

• List symptoms, signs & explain diagnostic

work-up

15 minutes

• Describe “best practice” management

approaches including pharmacologic

treatments

15 minutesSecor 2019 copyright

Case Study

30 year old for Annual Exam

• OC in past, side effects

• 3, 4 menses year

• Irregular menses since

Menarche age 12

• Married in 1 year

• Pregnancy NOT desired yet

• Both Parents w Diabetes

and Overweight


PCOS: Introduction

• Most common reproductive endocrine disorder

• 5 + million women in US

• 1 in 15 women (6-10%)

• Familial tendency

• Exposure in-utero, Environmental, Diet, Lifestyle, Stress

• Obesity (independent risk factor)

• Lean: ~10% (less well understood)

• Associated with serious sequelae:

– MS, Diabetes, CVD, Infertility, Cancer, Mental Health Problems, etc.


PCOS: Symptoms, Signs & Risks

• Oligomenorrhea: Highly predictive!

• Hyperandrogenism: Hirsutism, acne, (a-reductase)

• Obesity: esp. central obesity

• Infertility (25-37%) & Anovulation

• Abnormal Uterine Bleeding/AUB (new term)

• Uterine Cancer- 3 fold incr. risk (hyperplasia)

• Insulin Resistance, MS, Diabetes Type 2 (3-7x risk)

• Heart Disease, Hypertension; Dyslipidemia (70%)

• Mental Health Problems (Low allopregnanolone)



8

PCOS: Menstrual Irregularities

Classic Clinical Profile!Oligomenorrhea to amenorrhea

• History since menarche (CLASSIC)

• 6 or fewer “menses” per year

• BUT may have regular cycles

Stein Leventhal 1935- singular

entity/OVARY

• Persistant Anovulation

• PCOS is a sign, not a disease

• Pathogenesis still unclear! Secor 2019 copyright

PCOS: Definition and

Central Pathogenic Mechanism

2006 Androgen Excess and PCOS Society:

• PCOS is an Androgen Excess Disorder

• Of androgen biosynthesis, utilization, metabolism

• in ovaries & adrenal glands

• associated with Insulin Resistance

• and other Health Risks


NEW PCOS:

Pathogenesis & Assoc. Risks

• Insulin Resistance (IR) and Hyperinsulinemia

• IR induces ovarian androgen production;

Raising LH, incr. menstrual abnormalities

• Hyperandrogenism increases IR! (CYCLE)

• IR plays critical role in pathogenesis of Hyperandrogenism, Chronic Anovulation

And Cardiometabolic risks!!!Secor 2019 copyright

Pathophysiology of PCOS: Hirsutism

• Hyperinsulinemia (45-65% of PCOS pts)

• Lowers SHBG =Sex Hormone Binding Globulins

• Higher Androgen production (Free T)

leading to

• Increased Alpha-reductase in skin cells

• Testosterone to dihydrotestosterone: > potent T

• Causing acne, hirsutism, etc.


PCOS and the “Gut” 2018

NEW Research! • Androgens- affect Gut Microbiome

• > T = Less diverse GI microbiota !!!

• These changes may influence how the

pathophysiology of PCOS develops!

• More research needed to determine

effects of androgens on the gut

microbiome

• Total N=163, PCOS N=73Torres PJ et al. J Clin Endocrinol Metab. 2018 Jan 23.doi:

10.1210/jc.2017-02153.Secor 2019 copyright

https://academic.oup.com/jcem/advance-article/doi/10.1210/jc.2017-02153/4822208

Pathophysiology of PCOS: Ovary

Hyperinsulinemia,

Hyperandrogenism

• Causes the Pituitary to hyper secrete LH (not All)

TONIC levels of LH, FSH, Estrogen, Testosterone

• Estrogen/estrone, testosterone slightly elevated

• Estrogen/estrone blocks pituitary FSH, LH

• New follicles continuously stimulated,

but don’t fully mature= RARE ovulation

• LH and Testosterone -thickens ovarian tissue (theca)

• Insulin suppresses apoptosis: programmed cell death

• Hence PCOS develops, vicious cycle!!!!


PCOS Pathophysiology

Normal Cycle versus PCOS

Secor 2019 copyright 15

Pathophysiological Characteristics of the Polycystic Ovary Syndrome (PCOS)

Nestler J. N Engl J Med 2008;358:47-54


PCOS Case Study


• OC in past, side

effects



• Menarche age 12


• Pregnancy NOT

desired yet

• Both Parents w

Diabetes

Diagnostic

Workup/Labs?


Diagnosis of PCOS• Clinical presentation is sufficient!

– If NO virilizing symptoms

BUT

• Rule out associated conditions!

AND

• Variable presentation is common

• Rapid Hirsutism Onset: Full Work-up!!!

Genazzani. PCOS. Archives of perinatal medicine; 2012: 18 (1): 27-36.


Rotterdam Criteria 2004

2 of 3 required• Oligomenorrhea (esp. >3 months) or anovulation

• Hyperandrogenism:

Acne, hirsutism, central obesity

• NEW - Ultrasound: Polycystic Ovaries

12 follicles 2-9 mm

or increased volume >10ml in >1 ovary

25% of NORMAL women have ovarian cysts!

Rotterdam consensus group. Revised 2004 consensus criteria.

Fertil Steril 2004 Jan;81:19-25.


PCOS Ovary

Classic “string of pearls”


20

PCOS Diagnostic Work-up? • Body weight, BMI (>30), Waist (>35 inches), BP

• Pelvic ultrasound: Ovaries & hyperplasia>10mm

• Pregnancy test

• CBC, CMP incl, Lipids, CRP-hs, LFTs, TSH

• Random/Fasting Glucose, OGTT (best test)– Hgb-a1C: DM= >6.4, At risk = >5.6-6.4 !!!!

• Estradiol

• Total Testosterone: PCOS = > 60, Tumor > 200– Free T: PCOS= 2- 3%

• Prolactin 3-27ng/ml, FSH >30, DHEA-sulfate

• LH/FSH Ratio >3, but may be normal in PCOSNing, N et al. How to recognize PCOS: results of a web-based survey at IVF-worldwide.com.

Reproductive, BioMedicine Online (2013), http://dx.doi.org/10.1016/j.rbmo.2013.01.009


PCOS Differential: Cushing’s?• Cushing’s Disease (Pituitary)

• Cushing’s Syndrome (Adrenal)

• Symptoms/Signs: Slow-insidious onset similar to PCOS

– Central adiposity or obesity in general, hirsutism, absent

menses, acne, male pattern hair loss.

– Hypertension, hyperglycemia, dyslipidemia

– Differences: Wide purple striae, easy bruisability,

posterior cervical fat pad (buffalo hump), red round/puffy

face, muscle wasting of extremities

• Labs: May Order or Refer (based on your expertise)

1. Overnight Dexamethasone (1 mg) Suppression test

2. Late night Salivary Cortisol

3. (24 hour urine) for free cortisol and creatinine Secor 2019 copyright

Diagnosis of Metabolic Syndrome

Requires 3 Criteria

• B/P >130/85

• Abdominal obesity >35 inches

• Triglycerides >150 mg/dl

• HDL Cholesterol < 50 mg/dl

• Fasting Glucose 100-125 mg/dl = nl

• 2 hr GTT (75 gm load) 140-199 mg/dl


Glucose Testing

OGTT for ALL abnormal values

• Random elevations suggest a trend

• Fasting & Oral GTT required

• Fast 8 hours: 65-99 mg/dl = normal

• 100-125 = Impaired fasting glucose

• > 95 suspicious

• > 126, suspect DM, retest different day

• >140 mg/dl x 2 = Probable diabetes


PCOS Diagnostic Work-up

Preferred for PCOS:

• 2- hour Glucose Response GTT (75 gm load)

>140, < 200 mg/dl = Impaired Glucose

Tolerance

> 200 mg/dl = Non-insulin-dependent DM

• GTT abnormal: 2-8 years before DM

develops !

– Better than FBS

Speroff. PCOS. Dialogues in Contraception 2007;11(1): 5-7.

Diabetes Care 2004;27: S11-14.Secor 2019 copyright

Hgb A1C Guidelines per ADA

for Diabetes Diagnosis:

• Predictive screening tool !

• 5.6-6.4 = “At risk”

• > 6.5 = Diabetes

ADA. (2010 Jan). Diagnosis and classification of DM. 33(1), S62-S69.


Abnormal Uterine Bleeding (AUB)

• Comprehensive, focused history

• Many causes: PALM-COEIN classification

• Consider DIFFERENTIAL by AGE and HISTORY

• Post-menopause AUB:

- Any bleeding beyond 12 months since LMP

- Even “1 drop of blood” is concerning

- Must REFER to OBGYN to R/o cancer 9% risk!Secor 2019 copyright

Abnormal Uterine Bleeding (AUB)

Classification/Differential: PALM-COEIN

DIAGNOSIS: CAUSE: Consider by AGE:

Structural

P Polyps: > 30 years

A Adenomyosis: > 30

L Leiomyoma/ Fibroids: > 30

M Malignancy/Hyperplasia: > 40 (Obesity, DM, PCOS, >50 yr)

Non Structural

C Coagulopathy: Any age

O Ovulatory Dysfunction: Any age

E Endometrial Disorders: Any age

I Iatrogenic, Medications: Any age

N Not ClassifiedSecor 2019 copyright

EMB: When to Perform?

NOT Based on Age

• Duration of exposure to unopposed

estrogen? EXPLAIN

• If long standing anovulation then…

Risk of hyperplasia, atypia, cancer

When in doubt:

• Transvaginal US & endometrial biopsy!

– “Low threshold” regardless of age

– Do NOT trust JUST an ultrasound


Ovulatory vs Anovulatory Bleeding:

KEY

Ovulatory

• Premenstrual

symptoms

• Pattern for each

patient

• Bleeding pattern

• From episode to

episode

Anovulatory

• No premenstrual

symptoms

• No pattern

• Each bleeding

event differs


Ultrasound: If Endometrial Stripe > 10 mm

Must do EMB: Not Based on Age!

Menopause: Endom. stripe >5 mm - abnormal


Abnormal Uterine Bleeding:

• Amenorrhea (>6 months)

– Progestin challenge

– Medroxyprogesterone acetate 10 mg orally x 10-

12 days

– Withdrawal bleed, then OK

– No withdrawal bleed

– Give Combination OC (COC) x 1 month,

if bleed, OK

– If no bleed, REFER to Endocrinologist

(reproductive)


Case Study



effects


• Irregular menses

since

• Menarche age 12


• Pregnancy NOT

desired

• Both Parents w

Diabetes

Work-up/ Labs:

• BMI 32

• Waist 38 inches

• COC withdrawal bleed

• HDL 35 mg/dl

• LDL 130

• Triglycerides 210

mg/dl

• Fasting glucose 102

mg/dlSecor 2019 copyright

Team Approach to PCOS and

Individualized Management

• Primary care

• ObGyn

• Infertility

• Cardiovascular

• Diabetes/Endocrine

• Mental health

• Nutritionist

• Wellness coach?

• Contraception vs

Conception?

• Revisit regularly

• Fast track

fertility!!!


Case Study



effects



• Menarche age 12


• Pregnancy NOT

desired

• Both Parents w

Diabetes

Work-up/Labs:

Management plan:

• More labs/tests?

• Metformin ?

• Contraceptive ?

• Pregnancy?


Before PCOS Management:

Contraception or Conception?

• Discuss plans for future pregnancy

• Shouldn’t wait until age 35 to have 1st

baby


PCOS and Pregnancy Risks:Obesity is a “Ticking Time Bomb”

for Reproductive Health

• Infertility: 40% female/PCOS

• Spontaneous Abortion /SAB, (25-73%)

• Gestational Diabetes (3 x increased risk)

• Preeclampsia/Hypertension


Infertility in Obese pts with PCOS:

Lifestyle Approaches 1st Line

• Exercise:

• Weight loss: (>10%)

• Increases insulin sensitivity

• Improves ovulation & fertility

• This addresses role of hyperinsulinemia

in pathogenesis of anovulation

Genazzani. (2012). PCOS. Archives of perinatal medicine. 18 (1), 27-36.


Potential Uses for Metformin

• Adjunct to Clomiphene for CC-resistant patients

• First line agent for ovulation

• Reduction of miscarriage in patients with PCOS

May not help reduce SABs (spontaneous ab)

• May not reduce risk of Gestational Diabetes

(NEW)

• Alternative to OC for cycle regulation in PCOS

• Treatment of PCOS associated hirsutism

• Weight loss

• Reversing IR, hyperinsulinemia, etc.Secor 2019 copyright

Treatment Options: Metformin

• Biguanide 4+ decades worldwide

• Not FDA approved for PCOS

• BUT widely used for PCOS, and well studied

• Side effects & toxicity well studied

• Must check liver, renal function before use

• Insulin sensitizing effect

• Menses induction: 90% in 6 months

• Increases ovulation esp. w/ clomiphene/ letrozole

75% w Combo Rx

• NOT- Teratogenic: Cat B in pregnancy & lactation


Infertility and PCOS

Ovulation Doesn’t Equal Pregnancy!

• Easy to stimulate ovulation with

various meds

• Referral to Reproductive Endocrinology

is KEY

Early esp. with PCOS

And if “Older”

30-35 and esp. if >40 years old


PCOS: Cochrane Review 2010

Metformin Fertility Effects

Mixed:

• Benefits pregnancy & ovulation rates

• But NO evidence of improves live birth rates, used

alone or in combination with clomiphene, or when

compared with clomiphene

• Use of metformin to improve reproductive

outcomes in women with PCOS appears limited


PCOS and Pregnancy Risks

• Infertility

– Metformin helps

• Spontaneous Abortion

– Metformin may NOT help (new research)

• Gestational Diabetes

– Metformin may NOT help (Diabetic Care 6/2013)

• Preeclampsia

– Metformin helps


Aromatase Inhibitors: Preferred

Alternative to Clomiphene

• Letrozole (Fumera) OFF LABEL

• BUT preferred by infertility experts (1st line)

• Because:

• Well tolerated, few side effects

• Letrozole produces 1 follicle !!

• PCOS highly responsive to fertility meds

– Have “many eggs”

• Dosing; 5-7.5 mg oral daily, Day 2-6, x 5 days


NOT Desiring Pregnancy:

PCOS Treatment Approaches

• Life Style Changes: Weight loss, Diet, Exercise!

50% reduction in IR (WOW!)

• Combination Hormonal Contraceptives (CHC)

NEW; Low-androgen safer progestins;

Levonorgestrel (LNG), Norethindrone (NE),

Norgestimate (NGM)Vinodagrova et al. (2015, May 26). BMJ, 350:h2135

(http://dx.doi.org/10.1136/bmj.h2135)

• Insulin sensitizers: Metformin

30% reduction in IR

• Combination therapy: Metformin and CHC?Secor 2019 copyright

Weight Loss: KEY

• 5% loss: improves insulin sensitivity!

• Reduces Testosterone levels

• Improving Acne, Hirsutism, etc.

• Lowers BP, improves labs

• Enhances fertility!

• Return of regular menses (withdrawal bleed)

• Reduces Uterine Cancer risk!


Hirsutism and PCOS

• Combined hormonal contraceptives (CHC)

• Insulin sensitizers!

• Spironolactone: (Cat C): 25-100 mg orally bid ($)

Inhibits 5a-reductase, preventing T to DHT*

Incr. SHBG, decreasing free T

• Finasteride: (Cat D), 1mg oral daily (same as above)

• Eflornithine HCL: (Cat C): topically ($$$)

• Various hair removal techniques

*DHT = Dihydrotestosterone

Lindheim, PCOS, OBGYN Management, 2012;24 (12)


Hirsutism and PCOS: Cont’d

• Eflornithine HCL (Vaniqa) topical cream: $$$– “Hair growth retardant”

– Cat C

– Apply thin film BID, rub in thoroughly

– Do NOT wash area for 4 hours

• Finasteride (Propecia, Proscar): Effective, Off-label– Anti-androgenic, inhibits 5a-reductase, T to DHT

– Cat D

– Side effects: Depression, anxiety

– 1 mg oral daily: Reduces side effects (2.5-5 mg daily)



Combination Therapy for PCOS• Contraceptives: First line

– Combination hormonal contraceptives (CHC)

– Progestin only: Caution w DMPA (insulin resistance?)

– Intrauterine Contraceptives (IUC)

Plus:

• Insulin Sensitizers:

– Metformin XR 500-2250 mg oral daily @ hs (start low, go

slow)

Nestler, J. (2009 Jan). PCOS. NEJM, 358 (1).



Combination Hormonal Methods• To induce withdrawal bleed (pt thinks is menses)

• Prevent uterine cancer

• Suppress ovarian androgen production (T.)

• Provides symptom relief

• For oligomenorrhea, acne & hirsutism

• Improved BMI, glucose tolerance & basal insulin

• NEW: Possible increased risk of CV events

Lower E2, safer progestins: LNG, NE, NGM*

*LNG= Levonorgestrel, NE= Norethindrone, NGM= Norgestimate

Vinogradova et al (2015, May 26) BMJ, 350:h2135. (http://dx.doi.org/10.1136/bmj.h2135).

• If BMI > 30, VTE risk increased by x 3.5 fold !!!Secor 2019 copyright

PCOS: Metformin vs CHC*?• NEW 2016: Systematic review and meta-analysis

• 172 studies, 4 studies w 231 participants met criteria

• Based on very-low to low quality data

Findings:

• OC: Superior for regulation of Menses, and Acne

• Metformin: greater reduction in BMI, decreased

dysglycemia, lower LDL

• Neither superior for Hirsutism, lowering TG, incr HDL

• CHC = combination hormonal contraceptive

Al Khalifah, et al. PCOS, Teens. Pediatrics 2016 May; 137:e20154089


Progestin Only Methods and

PCOS • Medroxyprogesterone Acetate (MPA):

– An option esp. if estrogen is contraindicated

– May be associated with weight gain

– Possible impact of high-dose progestin on IR?

• Levonorgestrel IUC:

– Local endometrial effects- so probably OK

– Minimal systemic levels

• Etonogestrel Implant:

– Low systemic levels, so probably OK


Treatment Options: Metformin• Metformin = Biguanide

• Worldwide use commonly for 4+ decades

• Not FDA approved for PCOS BUT widely used

• Insulin sensitizing effect

– Decreases risk of progression from IGG to DM

– Metformin XR 500-2250 mg oral daily @ hs (slow

increase)

• Side effects & toxicity well studied

• Must check liver and renal function before use

• Category B in pregnancy; NO teratogenic risk

• Increases ovulation esp. w/ clomiphene/letrozole

• Consensus: Safe in pregnancy – Cat B


Metformin XR: Preferred

• Less side effects

• Improved lipid profile: Triglycerides, HDL, LDL

• Weight loss especially with higher doses !

• Easy dosing at HS/ bedtime

• Start low, go slow…

• Start 500 mg orally at HS

• Increase 500 mg weekly

• 2000-2250 mg daily maximum dose


PCOS: Menopause (NAMs)

• Systemic estrogen for hot flashes?

• Caution: subclinical cardiovascular disease!

– Transdermal estrogen may be safer than oral

– OR avoid systemic E2, use alternatives (NAMS)

– Progesterone 100 mg orally at hs helps sleep, hot

flashes, etc, fewer side effects than MPA*, may be safer

too *medroxyprogesterone acetate

• Vaginal symptoms: Pelvic PT (APTA.org)

– Vaginal estrogen: cream, tablets, ring (Estring)

– Non-estrogens: SERM Ospemifene (Osphena), DHEA PV

suppositories,

• Mona Lisa Touch laser (NEW FDA Warning, NEED RESEARCH)

– Pelvic PT (APTA.org)

– if superficial or deep dyspareunia doesn't resolve w meds aboveSecor 2019 copyright

PCOS: Prevention is KEY

• Early diagnosis

• Symptom relief

• Normalizing labs

• Obesity control

• Exercise

• Healthy diet (protein)

• Mental health

• Prevention of sequelae!!!Secor 2019 copyright

PCOS Objectives for Session Upon completion of this session attendees will be

able to:

• Discuss epidemiology, pathophysiology,

associated risks and complications

15 minutes

• List symptoms, signs & explain diagnostic work-

up

15 minutes

• Describe “best practice” management approaches

including pharmacologic treatments

15 minutes


Thank you

Thanks to Carol Lesser NP, Boston IVF

Patty Duprey NP, Tom Bartol NP

R. Mimi Secor, DNP, FNP-BC, FAANP

MimiSecor.Com

My App: text “DrMimi” to 36260


Resources

• www.PCOSsupport.org

• www.Soulcysters.org

• www.pcosstrategies.org

Patient Education:

• WWW.nih.gov

• www.acog.org

Weight Loss Ap:

• MyFitnessPalSecor 2019 copyright

References: Updated

• Guidi, J, Gambineri, A, Zanotti, L. Psychological aspects of

hyperandrogenic states in late adolescent and young

women. Clin Endocrinol 2015; 83: 872–878.

• Mcluskie,I. PCOS. BMJ 2017; 357:

doi: https://doi.org/10.1136/bmj.i6456

• Moran, LJ, Hutchison, SK, Norman, RJ. Lifestyle changes

in women with polycystic ovary syndrome. Cochrane

Database Syst Rev 2011; (7): CD007506.

• Pasquali, R. Contemporary approaches to the

management of PCOS. Therap Adv Endo/Metab

2018;9(4):123-134. https://doi.org/10.1177/2042018818756790

• Pasquali, R, Zanotti, L, Fanelli, F. Defining

hyperandrogenism in women with polycystic ovary

syndrome: a challenging perspective. J Clin Endocrinol

Metab. 2016; 101: 2013–2022.Secor 2019 copyright

https://doi.org/10.1136/bmj.i6456

https://doi.org/10.1177/2042018818756790

References:-Barry, J.A., Kuczmierczyk, A. R., Hardiman, P. J. (2011). Anxiety and

depression in polycystic ovary: a systematic review and meta-analysis.

Human Reproduction, 26(9): 2442-2451.doi:10.109/humrep/deq197

-Bates, G. W. (2012). Long term management of Polycystic Ovarian

Syndrome. Molecular and Cellular Endocrinology, 373(1-2):91-97. doi:

10.10101/j.mce.2012.10.029.

-Duleba, A. J. (2012). Medical management of metabolic dysfunction in

PCOS. Steroids, 77(4): 306.

-Veltman-Verhulst, S. M., Boivin, J. E., Eijkemans, M.J.C. & Fauser,

B.J.C.M. (2012). Emotional distress as a common risk in women with

polycystic ovary syndrome: a systematic review and meta-analysis of 28

studies. Human Reproduction Update, 18(6): 638-651.doi:

10.109/humupd/dms029.

-Yawn, V. (2012). Polycystic Ovarian Syndrome. Advance for NPs &

PAs, 3(12): 11-15.


References Bates G, Legro R. Longterm management of PCOS. Molecular and

Cellular Endocrinology. 2012.

http://dx.doi.org/10.1016/j.mce.2012.10.029,

Genazzani. PCOS. Archives of perinatal medicine; 2012: 18 (1): 27-36.

Harborne et al. PCOS. JClin Endocrinol Metab 2005; 90:4593

Nestler, J. PCOS. NEJM 2008; 358:47-54.

Ning, N et al. How to recognize PCOS: results of a web-based survey at

IVF-worldwide.com. Reproductive BioMedicine Online (2013),

http://dx.doi.org/10.1016/j.rbmo.2013.01.009

Romualdi D, et al. How Metformin Acts in PCOS Pregnant Women.

Diabetes Care. Jan 13, 2013;1-5.

Rotterdam consensus group. Revised 2004 consensus criteria.

Fertil Steril 2004 Jan; 81:19-25.

Speroff, L. and Mishell, D. PCOS: Management and contraception.

Dialogues in Contraception, Spring 2007; 11(1):5-7.


pcos update 2019: common, subtle, and more serious than ever · diagnosis of pcos • clinical...

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