••• Chapter 58^ Hyperandrogenism^585
❍ What are metformin’s mechanisms of action?
(1) To suppress hepatic glucose output; (2) to decrease intestinal absorption of glucose; (3) to increase insulin-
mediated glucose utilization in peripheral tissues; and (4) has an antilipolytic effect that decreases fatty acid
concentrations, as a result decreasing gluconeogenesis.
❍ What are the therapeutic effects of combined OCPs?
(1) A decrease in LH secretion and as a result a decrease in ovarian androgen production; (2) increased hepatic
production of SHBG with decreased free testosterone as a result; (3) decrease in adrenal androgen secretion;
(4) regular menses, resulting in preventing endometrial hyperplasia; and (5) progestins inhibit 5a-reductase activity
in skin that decreases DHT.
❍ Why should a birth control method always be used with spironolactone?
It has anti-androgen effects and may inhibit normal development of the external genitalia in a male fetus.
❍ For women who desire pregnancy and have PCOS with infertility, what would be some management
options?
(1) Weight loss and dietary modification, (2) Clomid, and (3) metformin and combined Clomid/metformin.
❍ What is the effect of metformin treatment during IVF in women with PCOS?
Metformin has been shown to improve pregnancy and live birth rates as well as reduce the risk of ovarian
hyperstimulation syndrome.
❍ How should metformin be dosed and what are some contraindications?
Because of GI side effects, the dose should be increased slowly to a maximum of 2000 mg qd with 1 to 2 weeks
elapsing between increases in doses. Contraindications: avoid in renal insufficiency, CHF, sepsis; it should be
stopped prior to IV contrast; should not be given with cimetidine as it competes for renal clearance; and creatinine
should be checked prior to starting metformin (and should be <1.4) and make sure normal fluid intake.
❍ What surgical treatments are available for the treatment of PCOS/hirsutism?
Historically, wedge resection was used, now in disfavor due to postoperative adhesions. Laparoscopic YAG
laser drilling of the ovary has been used with some success in otherwise medically refractory patients to induce
ovulation. Laparoscopic ovarian diathermy (electrocautery) was compared with gonadotropin therapy in two
randomized controlled trials, resulting in similar success rates (approximately 55% pregnancy rates), with lower
multiple gestation rates.
❍ When should surgical treatments be used?
When the only cause of infertility is PCOS and additional tubal factors, endometriosis and oligospermic male
partners have been excluded. Then the pregnancy rates are 80% to 87% compared with 14% to 29%. In addition,
Clomid and metformin should first be attempted, BMI should be <30, and women should have an increased LH
concentration of >10 IU/L.