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Wei Zhang
OB/GYN Hospital, Fudan University

 OVERVIEW of PCOS
 PATHOPHYSIOLOGY
 SIGNS and SYMPTOMS
 DIAGNOSTIC CRITERIA
 TREATMENT

 1 st described by Stein and Leventhal as a triad of amenorrhea, obesity and hirsutism (1935)
 The symptoms and severity of the syndrome vary greatly among affected women
 It is one of the leading causes of female infertility

 Definition :Polycystic ovarian syndrome is a common endocrine disfunction typified by oligo-ovulation or anovulation, signs of androgen excess, and multiple small ovarian cysts
 Abbreviations
 PCOS = Polycystic Ovarian Syndrome
 PCO= Polycystic Ovarian

 PCOS is the most common disorder of reproductive-aged women
 Affects approximately 4-12%
 PCOS appears to equally affect all races and nationalities


 Aggregation of the syndrome within families
 An increased prevalence has been noted between affected individuals and their sisters and mothers
 The first-degree male relatives of women with PCOS have significantly higher circulating DHEAS levels

 Environment causes
 Life style
 Exercise
 Diet
 Androgen exposure, et. al

 Interaction of Genetics and environment
PCOS may be a genetically determined ovarian disorder , the heterogeneity can be explained on the basis of interaction of the disorder with other genes and with the environment

Reproductive cycle regulated by HPO axis
FSH
Hypothalamus
GnRH
Gn
Pituitary
LH
Ovary
Progesterone
Estradiol
内膜

 Abnormal gonadotropin secretion
 Excess LH and low, tonic FSH
 Hypersecretion of androgens
 Disrupts follicle maturation
 Substrate for peripheral aromatization
 Negative feedback on pituitary
 Decreased FSH secreation
 Insulin resistance, Elevated insulin levels

 Increased GnRH from hypothalamus
 Excessive LH secretion relative to FSH by pituitary gland
 LH stimulates ovarian thecal cells to produce excessive androgen
 Ineffective suppression of the LH pulse frequency by estradiol and progesterone
 Androgen excess increases LH by blocking the hypothalamic inhibitory feedback of progesterone

GnRH androgen
Estrogen
LH
, FSH
Anovulation

 Intraovarian androgen excess results in excessive growth of small ovarian follicles
 Follicular maturation is inhibited
 Excess androgen causes thecal and stromal hyperplasia

PCO
 These "cysts" are actually immature follicles. The follicles development stopped at an early antral stage due to the disturbed ovarian function
 Polycystic is >12 follicles per ovary less than 10mm in diameter, ovary itself is enlarged

 Hyperinsulinemia
 Excess insulin production and insulin resistance
 Hyperinsulinemia contributes to hyperandrogenism through production in the theca cell and through its suppressive effects on sex hormone binding globulin production by the liver
 Hyperandrogenism vs. hyperinsulinemia: Which came first?
 Dyslipidemia

Downstream
Signal Defect
Autosomal
Dominant Gene GnRH
LH
PCOS
Insulin
Resistance
A=androgens, E2=estradiol
E2
A

 Hyperandrogenism
 Hirsutism
 Acne
 Chronic anovulation (irregular menses)
 Irregular menses
 Infertility
 Endocrine Dysfunction
 Obesity
 Insulin resistance
 Acanthosis Nigricans
 Impaired Glucose Tolerance and Type 2 Diabetes Mellitus
 Dyslipidemia
 Metabolic Syndrome and Cardiovascular Disease
 Polycystic ovaries

 Hirsutism, acne, male pattern balding, alopecia
 50-90% patients have elevated serum androgen levels
 Rare: increased muscle mass, deepening voice,

 Hirsutism:Ferriman-
Gallwey Scoring
System
 Acne: 50%
 Mild
 moderate
 severe

Chronic anovulation/oligo-ovulation
 Menstrual Dysfunction
 Oligomenorrhea : 70-75 %
 Amenorrhea: 20 %
 Regular cycles: 5-10 %
 Infertility : 30-70%

 Oligo or amenorrhea
 Menstrual irregularity typically begins in the peripubertal period
 Reduction in ovulatory events leads to deficient progesterone secretion
 Chronic estrogen stimulation of the endometrium with no progesterone for differentiation — intermittent breakthrough bleeding or dysfunctional uterine bleeding
 Increased risk for endometrial hyperplasia and/or endometrial CA

 Intermittent ovulation or anovulation
 Inherent ovarian disorder — studies show reduced rated of conception despite therapy with clomid

 Prevalence of obesity varies from 30-
75%
 2/3 of patients with PCOS who are not obese have excessive body fat and central adiposity
 Obese patients can be hirsute and/or have menstrual irregularities without having PCOS

 > 80% are hyperinsulinemic and have insulin resistance (independent of obesity)

•
Velvety plaques on nape of neck and intertriginous areas
• Epidermal hyperkeratosis
• Associated with insulin resistance

 Thickened sclerotic cortex
 Multiple follicles in peripheral location
 80% of women with PCOS have classic cysts

 Increased risk of developing Type 2
Diabetes and Gestational diabetes
 Low HDL and high triglycerides
 Sleep apnea
 Nonalcoholic steatohepatitis
 Metabolic syndrome — 43% of PCOS patients (2 fold higher than agematched population)
 Elevated heart disease
 Advanced atherosclerosis

 Short-term consequences
 Irregular menses
 Hirsutism/acne/androgenic alopecia
 Infertility
 Obesity
 Metabolic disturbances : Abnormal lipid levels/glucose intolerance
 Long-term consequences
 Diabetes mellitus (DM)
 Cardiovascular disease(CVD)
 Endometrial cancer

PCOS
hyperandrogen
Elevated insulin
Hirsutism, acne
Menstrual irregularity infertility
Obesity hyperplasia/cancer
CVD
Dyslipidemia diabetes

 Difficult to diagnosis
 Changing criteria
 Varying symptoms over time
 Not all women with PCOS have polycystic ovaries
(PCO), nor do all women with ovarian cysts have
PCOS
 although a pelvic ultrasound is a major diagnostic tool, it is not the only one
 The diagnosis is straightforward using the
Rotterdam criteria

 NIH Criteria(1990)
 Menstrual irregularity due to anovulation or oligo-ovulation
 Evidence of clinical or biochemical hyperandrogenism
 Hirsutism, acne, male pattern baldness
 High serum androgen levels
 Exclusion of other causes (CAH, tumors, hyperprolactinemia)

2003 Rotterdam Criteria (2 out of 3)
 Menstrual irregularity due to anovulation oligo-ovulation
 Evidence of clinical or biochemical hyperandrogenism
 Polycystic ovaries by US
 12 or more follicles measuring 2-9 mm in diameter
 Increased ovarian volume (>10 cm 3 )
 Exclusion of other causes (CAH, tumors, hyperprolactinemia)
European Society of Human Reproduction and Embryology and the
American Society for Reproductive Medicine (ESHRE/ASRM) redefined
PCOS

1.
Hyperprolactinemia
 Prominent menstrual dysfunction
 Little hyperandrogenism
2. Congenital Adrenal Hyperplasia
 morning serum 17-hydroxyprogesterone concentration greater than 200 ng/dL in the early follicular phase strongly suggests the diagnosis
 confirmed by a high dose (250 mcg) ACTH stimulation test: post-ACTH serum 17hydroxyprogesterone value less than 10 00 ng/dL

3. Ovarian and adrenal tumors
 serum testosterone concentrations are always higher than 150 ng/dL
 adrenal tumors: serum DHEA-S concentrations higher than 800 mcg/dL
 LOW serum LH concentrations
4. Cushing ’ s syndrome
5. Drugs: danazol; OCPs with high androgenicity

Clinical history (hair growth rate, onset of symptoms)
• Physical examination (hirsutism or virilization, rounded facies, buffalo hump)
• Laboratory testing (hormones)
• Ultrasonography (ovary, endometrium)

 Fasting glucose: elevated
 2 hour OGTT: elevated
 Fasting insulin: elevated
 Free testosterone: elevated
 DHEA-S: normal
 17-hydroxyprogesterone: normal
 Pelvic US
 Lipids profile

Total Testosterone (T)
DHEA-S (DS)
17-hyroxyprogesterone (17-OHP)
T Elevated
±
DS Elevated
PCOS
DS Elevated
Adrenal
T & DS Normal
Idiopathic
T > 200 ng/dl
DS > 700 μg/dl
Suspect Tumor
17-OHP > 2 ng/ml
Suspect CAH

 Goals of PCOS Treatment
 Restoration a normal cycle and fertility
 Lowering of insulin levels
 Treatment of hirsutism, acne
 Prenvention of endometrial cancer
 Prevention of DM,CVD and metabolic syndrome

 Lifestyle modification
 Anti-androgens
 Insulin lowering agents
 Induced ovulation-for pregnancy desired

 Weight loss:
 Low-carbohydrate diets
 sustained regular exercise
 90% of anovulatory women restored to full ovulation despite relatively small amounts of weight loss following exercise and change of diet
 BMI of 21 is ideal but the patient often respond to much less stringent body mass index

 OCPs: first option when fertility is not desired
 Decrease in LH secretion and decrease in androgen production
 Increase in hepatic production of sex-hormone binding globulin(SHBG)
 Decreased bioavailablity of testosterone
 Decreased adrenal androgen secretion
 Regular withdrawal bleeding
 Prevention of endometrial hyperplasia

 Spironolactone, 50-200 mg per day
 Androgen receptor blockade
 Steroid enzyme inhibition
 Aldosterone antagonism
 Lower blood pressure
 Potassium sparing

 progesterone withdrawal: every 1 to
3 months
 Regular withdrawal bleeding
 Prevention of endometrial hyperplasia and cancer
 regimens include
 MPA: 5 to 10 mg daily for 10-14 days
 Micronized progesterone: 200 mg each evening for 10-14 days

 Induction of ovulation
 Some reduced hair growth
 Improved glucose utilization
 Lowered serum insulin
 Lipid lowering properties

 Metformin
 Dosage: 1500-2550 mg per day
 Clinically significant responses not regularly observed at doses less than 1000 mg per day
 Treat with cyclic progestin to reduce endometrial hyperplasia if regular menses not attained
 10 mg for 7 to 10 days every one to three months

 Weight loss — reduction in serum testosterone concentration and resumption of ovulation
 Clomid: 80% will ovulate, 50% will conceive
 Metformin
 will restore ovulation and menses in > 50% of patients
 added to clomid, improves ovulatory rates
 CC/FSH/hCG
 Laparoscopic surgery: wedge resections, laparoscopic ovarian laser electrocautery
 IVF

 Pathophysiology
 Clinincal Features of PCOS
 Diagnosis criteria
 Treatment Option of PCOS

 References
 John O. Schorge . Williams Gynecology,2008
ISBN 978-0-07-147257-9
 丰有吉 . 妇产科学，八年制本科教材，人民卫
生出版社， 2008
 曹泽毅 .
中华妇产科学 . 人民卫生出版社 .2005