POLYCYSTIC OVARY SYNDROME

I. Consensus definition of PCOS--2 or more of the following (The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.  Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome  Fertil. Steril. 81:19, 2004)

  1. Oligo- or anovlulation
  2. Clinical and/or biochemical signs of hyperandrogenism
  3. Polycystic ovaries and exclusion of other etiologies (e.g. congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome)

II. Clinical features--Familial tendency has been suggested in some studies

  1. Hyperandrogenism
  1. Hirsutism, acne, male-pattern alopecia
  2. Elevated serum testosterone, androstenedione (us 50-150% higher than nl; can have nl seru, testosterone but elevated free testosterone)
  3. Probably ovarian in origin (as opposed to adrenal)
  1. Anovulation
  1. Not universal! There are women with polycystic ovaries and hyperandrogenism who have nl periods
  2. Amenorrhea, oligomenorrhea, or DUB
  3. Infertility
  4. Elevated LH (FSH us. low or nl); prob. secondary to ovarian dysfunction
  5. Have high levels of unopposed estrogen; this may put women at risk of endometrial carcinoma
  1. Obesity (common but not universal)
  2. Polycystic ovaries
  1. 22% of 257 "nl" volunteers had polycystic ovaries on u/s, but 94% of them had at least 1 symptom of PCOD, e.g. irreg. menses, hirsutism
  1. Hyperinsulinemia and insulin resistance
  1. Unclear why
  1. Doesn't seem to occur in women with polycystic ovaries and hyperandrogenism but nl periods!
  2. Independent of obesity
  1. Can see acanthosis nigricans on Px; this helps to r/o adrenal androgen-secreting tumor as cause of hyperandrogenism
  2. Risk of Type II DM seven times greater than gen'l population!
  3. May be the cause of the hyperandrogenism, both directly from hyperinsulinemia and through decreasing synthesis of sex hormone-binding globulin

III. Diff. dx

  1. Must distinguish from other hyperandrogenic states
  2. If serum testosterone > 200ng/dl suggests androgen secreting tumor
  3. If serum DHEA-S (dehydroepiandrosterone sulfate) > 7,000ng/dl suggests adrenal tumor
  4. If serum 17-hydroxyprogesterone > 800ng/dl suggests 21-hydroxylase deficiency; if < 200-800, suggests CAH
  5. Note that Valproic Acid may cause PCOS

IV. Treatment

  1. Weight loss--Will tend to improve all aspects of the disease
  2. For infertility, try to induce ovulation
  1. Antiestrogens, e.g. Clomiphine
  2. Insulin-Sensitizing agents
    1. Metformin
      1. Metformin 500mg/d resulted in much higher rates of ovulation than placebo in one 5wk study of 61 women with PCOD and infertility (NEJM 338:1876, 1998--JWWH)
      2. Metformin increased ovulation rate in women with PCOS and anovulation (Fertil. Steril. 75:310, 2001--JW)
      3. Metformin 500mg TID ass'd with sig. improvements in hirsutism, obesity, and menstrual cycle frequency (Eur. J. Endocrin. 147:217, 2002--cited in Med. Lett. 45:35, 2003)
    2. 410 pts with PCOD randomized to Troglitazone 150-600mg/d vs. placebo x 44wks. Troglitazone tx ass'd with dose-dependent increase in ovulation rates, sig. more pregnancies, sig. less hirsutism, and sig. lower fasting insulin and free testosterone levels. (J. Clin. Endo. Metab. 86:1626, 2001--JW)
  3. Gonadotropins-low-dose regimens may reduce risk of multiple gestation
  4. Pulsatile GnRH administration
  5. Laparascopic laser diathermy (no better than gonadotropin tx in one head-to-head study; Clin. Endocrinol. 33:585, 1990)
  1. For oligo- or amenorrhea or DUB
  1. Since risk of endometrial Ca is theoretically there, advisable to cycle with Oral Contraceptives or just cyclical progestins
  1. Avoid progestins with intrinsic androgenic activity b/c may worsen androgenic sx of PCOD
  2. OC's may be better than just progestins because the exogenous estrogens may reduce ovarian androgen production
  1. If not, consider regular u/s to monitor endometrial thickness (no clinical trials, just author's suggestion)
  1. For androgenic sx
  1. Spironolactone (may cause erratic uterine bleeding, so sometimes given along with OC's
    1. In a randomized trial in 69 women with PCOS randomized to spironolactone 50mg/d vs. metformin 1000mg/d, spironolactone was ass'd with greater improvements in hirsutism, increased frequency of menstrual periods, and less side effects (J. Clin. Endocr. Metab. 89:2756, 2004--JW)
  2. Note--antiandrogens can cause lethargy, mood swings, loss of libido
  3. Can take up to 5 mos to show change in hair growth; maximal effects may take 18mos or longer

V. Other

  1. Consider screening for glucose intolerance, e.g. w/ HbA1c or GTT, esp. if obese
  2. Screen for dyslipidemias

(NEJM333:853, 1994)