Clomiphene and Dexamethasone
October 1, 2006 3 minutes read
Clomiphene and Dexamethasone
Abstract & Commentary
By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: The addition of a high dose of dexamethasone effectively achieves ovulation and pregnancy in clomiphene-resistant patients.
Source: Elnashar A, et al. Clomiphene citrate and dexamethasone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. Hum Reprod. 2006;21:1805-1808.
Elnashar and colleagues in Egypt performed a randomized trial assessing the efficacy of adding dexamethasone to clomiphene citrate treatment (up to 150 mg/day). The subjects were 80 women with polycystic ovaries who had demonstrated resistance to clomiphene induction of ovulation and who had normal levels of dehydroepiandrosterone sulfate (DHAS). Both groups received clomiphene 100 mg/day from days 3 to day 7; in one group dexamethasone 2 mg/day was added from day 3 to day 12 and the other received a placebo. After only one treatment cycle, 75% of the clomiphene-dexamethasone group ovulated compared to 15% in the placebo group, and 40% of the treated group became pregnant compared with 5% of the placebo group.
Commentary
The next step after failing to respond to clomiphene can be expensive and complicated (gonadotropin treatment or laparoscopic surgery). It is worthwhile, therefore, to pursue a less costly and safer alternative. The efficacy of adjuvant treatment with glucocorticoids has been reported for over 20 years. The earliest experience indicated that this treatment was most efficacious in women who had elevated serum levels of DHAS. Subsequently, an effective response was documented in women with normal levels of DHAS and in unselected populations of clomiphene-resistant women.
The largest randomized trial thus far reported included over 200 clomiphene-resistant anovulatory women; 80% of the women receiving combined treatment with clomiphene and dexamethasone ovulated compared with 20% in the placebo group, and the pregnancy rate in the treated group was 40% compared with 4% in the control group.1
Empiric treatment with the combination of clomiphene and dexamethasone is therefore justified for 3 to 6 cycles. The evidence indicates that it is sufficient to limit the addition of the dexamethasone (with the high dose of 2 mg/day) to the follicular phase, thus eliminating side effects. The mechanism of the glucocorticoid effect is unknown. It is probably more than a simple suppression of androgen levels, including direct developmental effects on the ovarian follicle.
Of course many anovulatory women with polycystic ovaries have insulin resistance, and metformin treatment is indicated for this group. Some argue that these women should be treated first with metformin for 3 months and clomiphene added when ovulation fails to occur. Others advocate reserving metformin for those women who have demonstrated clomiphene resistance. Both approaches are acceptable. In view of the lesser cost and the absence of side effects, one can also argue in favor of an initial combination of clomiphene and dexamethasone for clomiphene-resistant patients. At the present time, there are no known laboratory or clinical parameters that can predict which patients are the best candidates for adjuvant dexamethasone. An empiric approach is justified.
Reference
- Parsanezhad ME, et al. Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial. Fertil Steril. 2002;78:1001-1004.
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