- Clinical science
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).
- Frequency: 6–10% of women in their reproductive years
Epidemiological data refers to the US, unless otherwise specified.
- The exact pathophysiology is unknown.
Reduced insulin sensitivity (peripheral insulin resistance) is present in PCOS, as in metabolic syndrome → hyperinsulinemia
Hyperinsulinemia results in:
- Epidermal hyperplasia and hyperpigmentation (acanthosis nigricans)
Increased androgen production in ovarian theca cells → imbalance between androgen precursors and the resulting estrogen produced in granulosa cells
- Increased LH secretion disrupts the LH/FSH balance → impaired follicle maturation and anovulation/oligoovulation
- Increased androgen precursor release → virilization and a reactive increase in estrogen production in adipose tissue
- Inhibits the production of SHBG (sex hormone-binding globulin) in the liver → ↑ free androgens and estrogens
- Hyperinsulinemia results in:
Hyperandrogenism in women is most commonly caused by PCOS!References:
- Onset typically during adolescence
- Menstrual irregularities (primary or secondary amenorrhea, oligomenorrhea)
- Difficulties conceiving or infertility
- Obesity and possibly other signs of
- Androgenic alopecia
- Acne vulgaris and oily skin
- : hyperpigmented, velvety plaques (axilla, neck)
- Mood and anxiety disorders
Voice change may occur in severe forms of PCOS. However, it typically suggests a different underlying cause of hyperandrogenism!
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)
- Oligo- and/or anovulation
- Polycystic ovaries on ultrasound
Blood hormone levels
- ↑ Testosterone (both total and free) or free androgen index
- ↑ LH (LH:FSH ratio > 2:1)
- ↑ DHEA-S (dehydroepiandrosterone sulfate)
- ↑ 17-HPO (17-hydroxyprogesterone), ↓ progesterone
- Estrogen is normal or slightly elevated
A clinical picture of hyperandrogenism overrules any normal hormone levels and can fulfill a diagnostic criterium of PCOS!
Evaluate for metabolic disease
- Test for hypertension
- Monitor BMI
- Assess for insulin resistance or type 2 diabetes mellitus → oral glucose tolerance test
- Assess for hyperlipidemia → measure serum lipids
- Enlarged ovaries with numerous anechoic cysts (polycystic ovaries)
- "String of pearls” appearance
- At least 12 subcapsular cysts
- Maximum diameter of the cysts: 9 mm
- Relative increase of stromal tissue with increased ovarian size: at least 10 mL
All conditions that are associated with menstrual cycle changes and signs of virilization should be ruled out before diagnosing PCOS:
- Thyroid disorder
- Follicular insufficiency
- Congenital adrenal hyperplasia
- Cushing's disease
- Pituitary adenoma
- Exogenous androgen intake
- Exogenous steroid intake
The differential diagnoses listed here are not exhaustive.
The therapeutic approach in PCOS is broadly based on whether or not the patient is seeking treatment for infertility.
If treatment for infertility is not sought: therapy aimed at controlling menstrual, metabolic, and hormonal irregularities
If the patient is overweight (BMI ≥ 25 kg/m2)
- First-line: weight loss via lifestyle changes (e.g., dietary modifications, exercise)
- Second-line (as an adjunct): ± metformin therapy (off-label)
- If the patient is not overweight:
- Adjunct treatment for hirsutism: eflornithine cream and/or laser ablation
- If the patient is overweight (BMI ≥ 25 kg/m2)
If seeking treatment for infertility
- Ovulation induction with clomiphene citrate or letrozole (off-label)
- If the patient is overweight: advise weight loss
- Second-line: ovulation induction with exogenous gonadotropins (low-dose regimen) or laparoscopic ovarian drilling