• Clinical science

Polycystic ovary syndrome (Stein–Leventhal syndrome…)

Abstract

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).

Epidemiology

  • Frequency: 6–10% of women in their reproductive years

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

  • The exact pathophysiology is unknown.
  • Reduced insulin sensitivity (peripheral insulin resistance) is present in PCOS, as in metabolic syndromehyperinsulinemia
    • Hyperinsulinemia results in:

Hyperandrogenism in women is most commonly caused by PCOS!References:[1][2][3]

Clinical features

Voice change may occur in severe forms of PCOS. However, it typically suggests a different underlying cause of hyperandrogenism!

References:[4][5][6]

Diagnostics

Diagnostic criteria

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

Diagnosis of PCOS is possible without the presence of ovarian cysts!
Rule out any other causes of hyperandrogenism and anovulation (see “Differential diagnoses” below).

Blood hormone levels

A clinical picture of hyperandrogenism overrules any normal hormone levels and can fulfill a diagnostic criterium of PCOS!

Evaluate for metabolic disease

Transvaginal ultrasound

  • 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

References:[7][5][8][9]

Pathology

The histological characteristics of PCOS are:

References:[5][10][11]

Differential diagnoses

All conditions that are associated with menstrual cycle changes and signs of virilization should be ruled out before diagnosing PCOS:

The differential diagnoses listed here are not exhaustive.

Treatment

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): combined oral contraceptive therapy ± metformin therapy (off-label)
    • If the patient is not overweight: combined oral contraceptive therapy
    • Adjunct treatment for hirsutism: eflornithine cream and/or laser ablation
  • If seeking treatment for infertility
    • First-line
      • Ovulation induction with clomiphene citrate or letrozole (off-label)
        • Clomiphene inhibits hypothalamic estrogen receptors, thereby blocking the normal negative feedback effect of estrogen → increased pulsatile secretion of GnRH → increased FSH and LH, which stimulates ovulation
      • If the patient is overweight: advise weight loss
    • Second-line: ovulation induction with exogenous gonadotropins (low-dose regimen) or laparoscopic ovarian drilling
    • Third-line: assisted reproductive technology

References:[5][12][13][14][15][16][17][18][19]

Complications

References:[5]

We list the most important complications. The selection is not exhaustive.