Nejm 2005;352:1223

Cause: Probable genetic autosomal dominant

Pathophys:

Hyperandrogenism + anovulation

Obesity induces and/or exacerbates by increased conversion of androstenedione to estrone in fatty tissues, which causes pituitary FSH suppression and increased LH; this leads to ovarian LH-stimulated androgen production, which in turn causes follicle atrophy and further stimulation of peripheral fat conversion to more estrone. More common in insulin-dependent diabetes because insulin resistance stimulates ovarian conversion of steroids to androgens (Nejm 1998;338:1876; 1996;325:617, 657); or IDDM may cause the syndrome by deficiency of a D-chiro-inositol–containing phosphoglycan, which mediates insulin action (Nejm 1999;340:1314)

Abnormally high LH levels induce ovarian thecal cell synthesis of 17-hydroxylase and C-17,20-lyase (see Important Steroid Pathways), causing increases in 17-OH progesterone, estrone, and androstenedione, which in turn cause further LH surges and masculinization (Nejm 1992;327:157; 1989;320:559)

Present in 1.5% of infertile patients, 75% of anovulatory women, 87% w hirsutism; only 2.8% of patients with polycystic ovaries by laparoscopy have the syndrome. Increased prevalence in obesity, seizure pts, esp those on valproic acid, 50% of whom have it (Nejm 1993;329:1383); and in IDDM often w insulin resistance

Sx: Syndrome onset at menarche. Oligo- or amenorrhea (80%); infertility (35-75%); obesity (37%); hirsutism (65%); acne (25%); visual acuity sx. Dysfunctional uterine bleeding.

Si:Withdrawal bleeding with progesterone; large ovaries, palpable if not too obese; hirsutism usually without masculinization. Astigmatism, myopia, hyperopia? Obesity

Endometrial cancer; possibly higher incidence of coronary artery disease (Ann IM 1997;126:32) and ASCVD in general; HT; diabetes; infertility

Lab:

Usually unnecessary; diagnose clinically

Chem: Total testosterone (>2 SD above mean); LH elevated, or high normal; glucose intolerance, incr lipids. Androstenedione level if suspect adrenal tumor, eg, onset in 30s; to r/o other causes: TSH and prolactin

Path: Ovaries 2-3 × normal size, cystic follicles; microscopically show variable theca cell hyperplasia and luteinization

Xray: Pelvic ultrasound may show polycystic ovaries

Rx:

Weight reduction and exercise, if obese, is 50% effective;

Meds:

• Birth control pills, esp those w minimally androgenic progesterones like norgestimate and desogestrel, plus:
• Spironolactone 200 mg po qd; or similar, drospirenone w ethinyl estradiol in bcp (Yasmin)
• Metformin 500-850 mg po tid decr testosterone and incr menses, improves LDL (Arch Peds Adolesc Med 2006;160:241; Nejm 1996;335:617, 657), esp if insulin-resistant diabetes present, as it often is
• Glitazones, which lower insulin levels that drive peripheral estrogen to androgen conversion, but cause weight gains
• Medroxyprogesterone 10 mg qd or other progesterone × 10 d q 1-3 mo to prevent endometrial cancer

of hirsutism (above plus Hirsutism/Hypertrichosis)

of infertility Female Infertility: clomiphene 50-100 mg po bid best, 22% pregnancy rate in 6 mo; and/or insulin secretion inhibition w metformin XR 1 gm po bid (Nejm 2007;356:551), 7% pregnancy rate in 6 mo; or human gonadotropin/menotropins (Pergonal); rarely wedge resections or laser drill holes of ovary done