Polycystic Ovarian Syndrome
(PCOS)
MBChB yr 6
Introduction
• Polycystic ovary syndrome (PCOS) is the most
common metabolic abnormality reproductive age
women
• One of most common cause of infertility in
women
• A number of genomic variants has been
associated with PCOS
• Non-genetic factors such as nutrition and physical
activity have strong influence on the
development of PCOS
Characteristics
• PCOS characterized by:
• Oligoamenorhoea / amenorrhoea
• Signs androgen excess e.g. acne, hirsutism
• Laboratory criteria of
– Hyperandrogenemia
– Hyperinsulinemia
• Polycystic ovaries on US
Criteria for diagnosis
ROTTERDAM CRITERIA (2003)
• 2 out of 3 of the following
– Polycystic ovaries (>12 peripheral follicles or increased
ovarian volume >10cm3)
– Oligo- or anovulation
– Clinical and/or biochemical signs of hyperandrogenism
– And exclusion of other etiologies such as
hypothyroidism, hyperprolactinemia, congenital
adrenal hyperplasia, cushing syndrome, androgen
secreting tumors
Pathogenesis
• Abnormal Pituitary Function— Altered Negative
Feedback Loop
– Increased GnRH from hypothalamus
– Excessive LH secretion relative to FSH by pituitary
gland
– Ineffective suppression of the LH pulse frequency by
estradiol and progesterone
• LH stimulates excessive androgen production
– Intraovarian androgen excess causes excessive growth
of small ovarian follicles
– Inhibition of follicular maturation
– Thecal and stromal hyperplasia in ovary
Pathogenesis
• Hyperandrogenism causes:
– Reduced sex-hormone-binding globulin (SHBG) resulting in
more free testosterone
– Insulin insensitivity
– Lipid abnormalities
– Abdominal obesity
– Symptoms of androgen excess
• 50-90% patients have elevated serum androgen levels
• Causes hirsutism, acne, male pattern balding, alopecia
• Deepening voice, clitoromegaly
Pathogenesis
• Insulin resistance
– Genetic link
– Mutation of the insulin receptor gene in the peripheral
target tissues, results in hyperinsulinemia
– Favors anovulation, reduced SHBG and androgen excess
– Insulin resistance in PCOS is independent of obesity
– Increased risk for impaired glucose tolerance and type 2
DM in PCOS women
– Obese women with PCOS tend to be more insulin resistant
than normal-weight counterparts
– Linked with metabolic syndrome and abdominal obesity
Presentation
• MENSTRUAL DYSFUNCTION
– Oligo or amenorrhea typically begins in the
peripubertal period
– Reduction in ovulatory events leads to deficient
progesterone secretion
– Chronic estrogen stimulation of the endometrium
with no progesterone results in intermittent
breakthrough bleeding or DUB
– Increased risk for endometrial hyperplasia and/or
endometrial CA
Presentation
• Hirsutism, male type hair growth
– Ferriman Gallaway score >8
• 9 areas(upper lip, chin, chest, back, abdomen, arms,thighs)
• Score 1-4
• 0-absence of terminal hair
• 4-extensive terminal hair growth
• Acne
• Baldness
• Central Obesity
• Acanthosis Nigricans
Investigations
• Hyperandrogenism
– Elevated total testosterone
• Most values in PCOS <150 ng/dl (if >200 ng/dl, consider
ovarian or adrenal tumor)
– LH/FSH ratio
– Levels vary over menstrual cycle, released in
pulsatile fashion, affected by OCPs
– LH/FSH ratio >2 has little diagnostic sensitivity
Lab investigations
• Hyperinsulinemia
– Fasting glucose level of 5.6 to 6.9 mmol/L
– Glucose level of 7.8 mmol/L to 11.0 mmol/L after
75 gm glucose challenge test
– Stimulated testing with OGTT may be more
sensitive than fasting measurements
– Levels above that suggests diabetes
Investigations
• Metabolic Syndrome
– Waist circumference:
• Women>88 cm (>35 in)
– Triglycerides >150 mg/dL
– HDL cholesterol:
• Women<50 mg/dL
– Blood pressure 130/ 85 mm Hg
– Fasting glucose > 5.6 mmol/L
Presence of any 2 of 5 criteria
Investigations
• Ultrasound
– Increased ovarian area (>5.5 cm2) or volume (>11 ml)
with presence of:
– >12 follicles measuring 2-9 mm in diameter
– Thickened sclerotic cortex
– Multiple follicles in peripheral location
– Polycystic ovaries not specific for PCOS
– 80% of women with PCOS have classic cysts
– Approx 20% normal women have incidental polycystic
ovaries
Polycystic ovaries, US
Polycystic ovaries; lapscope
Differential Diagnosis
• 1. Hyperprolactinemia/ hypothyroidism
– Prominent menstrual dysfunction
– mild hyperandrogenism
• 2. Congenital Adrenal Hyperplasia
– morning serum 17-hydroxyprogesterone
concentration greater than 200 ng/dL in the early
follicular phase strongly suggests the diagnosis
Differential Diagnosis
• 3. Ovarian and adrenal tumors
– serum testosterone concentrations > than 150
ng/dL
– adrenal tumors: serum DHEA-S concentrations >
800 mcg/dL
– LOW serum LH concentrations
• 4. Cushing’s syndrome
• 5. Drugs: danazol; OCPs with high
androgenicity
Treatment
• Depends on the main symptom to be addressed
• Acne
• Obesity
• Menstrual abnormality
• Hisrutism
• Long-term issues
– Insulin resistance
– Cardiovascular risk
– Obstructive sleep apnea
– Malignancy risk
Treatment
• Life style modification
• Diet and exercise
– In patients with PCOS who are obese, endocrine
metabolic parameters markedly improve after 4-12
weeks of dietary restriction
– Their SHBG levels rise and free testosterone levels fall
by 2-fold
– Serum insulin and IGF-1 levels also decrease
– Weight loss in patients with PCOS who are obese is
associated with a reduction of hirsutism and a return
of ovulatory cycles in 30% of women
– Target weight loss is 5% or more
Treatment
• Metformin
– Useful particularly in those who are overweight or obese
– Improves many metabolic abnormalities in PCOS and may
improve menstrual cyclicity and the potential for
pregnancy
– Improves insulin resistance and decreases
hyperinsulinemia in patients with PCOS
– Pretreatment with metformin has been shown to enhance
the efficacy of clomiphene for inducing ovulation
– The usual starting dose is 500 mg BD
– Target—1500-1800 mg / day
Treatment
• Combination estrogen-progestin pill first line
when fertility is not desired. MOA:
– Decrease in LH secretion and decrease in androgen
production
– Increase in hepatic production of sex-hormone
binding globulin
– Decreased bioavailablity of testosterone
– Decreased adrenal androgen secretion
– Regular withdrawal bleeds
– Prevention of endometrial hyperplasia
Treatment
• Anti androgens
• Mechanical hair removal
Plucking/shaving/electrolysis/laser
• Long term effects
– Cardiovascular Risk
• Increased prevalence of HTN
• Dyslipidemia (↑ TG, ↓ HDL, ↑ LDL)
• Predisposition to macrovascular disease and
thrombosis
• Multidisciplinary management
Treatment
Long term effects
• Obstructive Sleep Apnea (OSA)
– 30-fold increased risk of OSA, not explained by obesity
alone
– Insulin resistance strongest predictor of OSA (not BMI,
age, testosterone)
• Risk for malignancy
– 3 fold increased risk endometrial carcinoma in PCOS
– Increased risk of ovarian and breast cancer
– Warrants regular screening