Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hyperandrogenism, oligoovulation/anovulation, and/or the presence of polycystic ovaries. The diagnosis of PCOS is made following exclusion of disorders that may present with a similar clinical picture (e.g., congenital adrenal hyperplasia), most commonly by hormone analysis. Up to 50% of PCOS patients have metabolic syndrome, which is associated with obesity, insulin resistance, hypercholesterolemia, and an increased risk for endometrial cancer. PCOS primarily manifests with hirsutism, acne, and virilization. Diagnostic methods include a pelvic exam, blood tests for specific hormones, and ultrasound. Management consists of weight loss via lifestyle changes, and oral contraception pills are indicated in women who do not wish to conceive. The aim of treatment in women who desire to conceive is to normalize ovarian function and stimulate follicular growth (e.g., with clomiphene).
- Prevalence: 6–12% of women in their reproductive years in the US 
Epidemiological data refers to the US, unless otherwise specified.
- The exact pathophysiology is unknown.
- Strong association with obesity → ↑ in peripheral estrogen synthesis from adipose tissue and ↓ in peripheral sensitivity to insulin 
Reduced insulin sensitivity (peripheral insulin resistance) and the consequent hyperinsulinemia result in:
- Epidermal hyperplasia and hyperpigmentation (acanthosis nigricans) 
- ↑ Androgen production in ovarian theca interna cells → imbalance between androgen precursors and the resulting estrogen produced in granulosa cells
- Inhibition of SHBG in the liver → ↑ free androgens and estrogens 
Hyperandrogenism in women is most commonly caused by PCOS.
Onset of symptoms typically occurs during adolescence.
- Menstrual irregularities
- Insulin resistance and associated conditions
- Skin conditions
- Anxiety disorders
Voice change may occur in severe forms of PCOS. However, it typically suggests a different underlying cause of hyperandrogenism.
- Multiple, brown cysts arranged in a circular pattern in the subcapsular region of the ovary
- Cysts are relatively small and of approximately the same size
- Ovarian hypertrophy with thick capsule
- Stromal hyperplasia and fibrosis
- Multiple enlarged cystic follicles
- Hyperluteinized theca cells
- Decreased granulosa cell layer
- Definition: A state of excess androgen levels that causes symptoms such as growth of facial hair, deepening of the voice, and male-pattern baldness.
- For more information about physiological causes of hyperandrogenism, see “Pregnancy”
|Differential diagnosis of hyperandrogenism in females|
|PCOS|| || |
|Nonclassic CAH|| || || |
|CAH|| || |
|Cushing disease|| |
|Hypothyroidism|| || |
|Hyperprolactinemia|| || |
|Androgen-secreting tumor (e.g., Sertoli-Leydig cell tumor, adrenal)|| || |
|Acromegaly|| || |
| || |
| || |
|Drug-induced (e.g., exogenous steroid and androgen intake)|| || |
- Virilization: The appearance of male secondary sexual characteristics in a female individual
- Rapid onset of virilization is suggestive of exogenous androgen intake or androgen-secreting tumors
- Manifestations of the underlying condition
- Laboratory tests to identify hyperandrogenemia
- Investigate for the underlying cause
- Medication to suppress or block androgen and manage symptoms of virilization
- Treat the underlying cause (e.g., surgery for androgen-secreting tumors)
The differential diagnoses listed here are not exhaustive.
According to the American Association of Clinical Endocrinologists, at least two of three of the criteria below are required for diagnosis of PCOS after excluding other causes of irregular bleeding and elevated androgen levels.
- Hyperandrogenism (clinical or laboratory)
- Oligoovulation and/or anovulation
Enlarged, polycystic ovaries on transvaginal ultrasound
12 or more (sclerotic) cystic follicles with a diameter between 2 and 9 mm with “string of pearls” appearance
- Relative increase of stromal tissue with increased ovarian size (at least 10 mL)
- 12 or more (sclerotic) cystic follicles with a diameter between 2 and 9 mm with “string of pearls” appearance
Ovarian cysts are not required to diagnose PCOS.
Blood hormone levels
- ↑ Testosterone (both total and free) or free androgen index
- ↑ LH (LH:FSH ratio > 2:1)
- Estrogen is normal or slightly elevated
A clinical picture of hyperandrogenism fulfills a diagnostic criterion of PCOS, even in the absence of hormonal abnormalities.
Evaluate for metabolic disease
The therapeutic approach in PCOS is broadly based on whether the patient is seeking treatment for infertility.
- Weight loss: if patient is overweight (BMI ≥ 25 kg/m2) in order to reduce estrone production by the adipose tissue
- Dietary changes (especially through caloric restriction)
- Ovulation induction with letrozole; : higher clinical pregnancy and live birth rate when compared to clomiphene
- Alternative: clomiphene (inhibits hypothalamic estrogen receptors → disruption of normal negative feedback effect of estrogen → ↑ pulsatile secretion of GnRH → ↑ FSH and LH → stimulation of ovulation)
- Special consideration: metformin
If treatment for infertility is not sought
If no treatment for infertility is sought, therapy should be aimed at controlling menstrual, metabolic, and hormonal irregularities.
- Insulin-sensitizing drugs (metformin, pioglitazone, rosiglitazone)
- Combined oral contraceptive therapy (see above) and progestin
Treatment of hirsutism
- Cardiovascular disease
- Type 2 diabetes mellitus
- Increased cancer risk (before menopause) 
- Increased miscarriage rate
We list the most important complications. The selection is not exhaustive.