Clomiphene Citrate and Dexamethasone in Treatment of Clomiphene Citrate-Resistant Polycystic Ovary Syndrome: A Prospective Placebo-Controlled Study

Abstract

Traditionally, clomiphene citrate (CC) is the first-line treatment for the chronic anovulation that is part of polycystic ovary syndrome (PCOS). As many as one fourth of affected women, however, fail to ovulate in response to incremental doses of CC, and conception rates are far lower than ovulation rates. Many women resistant to CC lack overt signs of a treatable disorder. This study evaluated a short course of high-dose dexamethasone (DEX) when added to CC in 80 infertile women with CC-resistant PCOS. All participants had been infertile for at least 2 years and had normal levels of dehydroepiandrosterone sulfate (DHEAS). CC resistance was defined as failure of ovulation after 3 treatment cycles reaching 150 mg daily. CC was given in a dose of 100 mg daily from cycle day 3 to day 7. In addition, patients received either 2 mg daily of DEX orally from day 3 to day 12 of the cycle or folic acid placebo tablets. Transvaginal ultrasonography was used to detect ovarian follicles more than 18 mm in size. Human chorionic gonadotropin (hCG) was given in a dose of 10,000 U when at least one follicle of this size was detected, and women were advised to have timed intercourse. The actively treated and placebo patients did not differ significantly at the outset with regard to age, duration of infertility, body mass index (BMI), menstrual pattern, hirsutism, serum DHEAS, or day of hCG treatment. Steroid-treated women had more large follicles and significantly greater endometrial thickness than did placebo recipients. They also had significantly higher rates of ovulation and pregnancy. Three fourths of women given DEX and 15% of placebo recipients ovulated, and 40% and 5%, respectively, became pregnant. No patient described side effects from DMX. Women responding to DEX did not differ from nonresponders in age, time of infertility, or BMI. Responders did, however, have significantly higher rates of oligomenorrhea/amenorrhea and hirsutism. The investigators conclude that a significant number of CC-resistant infertile women with PCOS will benefit from adding a brief, high-dose course of DEX and that such treatment does not have adverse antiestrogenic effects. A trial of DEX would be appropriate before resorting to gonadotropin therapy or laparoscopic ovarian drilling.