Expert Commentary

Dexamethasone-clomiphene citrate (CC) treatment in CC-resistant PCOS patients

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References

The question:

Does dexamethasone-clomiphene citrate (CC) treatment improve ovulation rates in CC-resistant patients with polycystic ovary syndrome?

Past studies

This paper pays homage to the pioneering work of Riddick and colleagues who, almost 20 years ago, demonstrated that dexamethasone (DEX) therapy increased the rate of ovulation and conception in clomiphene citrate (CC)-resistant anovulatory patients with normal serum dehydroepiandrosterone sulfate (DHEAS) levels.1 Since then, several mechanisms have been proposed to explain this phenomenon, including the ability of glucocorticoids to lower hypothalamo-pituitary luteinizing hormone (LH) secretion,2,3 suppress adrenal androgen production,4 and therefore reduce circulating androgen levels in hyperandrogenic women.5,6 Reducing ovarian androgen production while suppressing circulating DHEAS as a prehormone for ovarian steroidogenesis4 presumably lowers elevated intrafollicular androgen levels, which appear to impair folliculogenesis.

This study

Parsanezhad et al examined the efficacy of DEX in conjunction with CC for inducing ovulation in CC-resistant polycystic ovary syndrome (PCOS) patients. Two hundred thirty infertile PCOS patients who failed to ovulate during CC therapy (250 mg/day orally for 5 days) and human chorionic gonadotropin (hCG) administration (10,000 units, intramuscularly) were randomized to CC (200 mg/day, cycle days 5-9) with or without DEX (2 mg/day, cycle days 5-14). Serum DHEAS levels, semen analysis, postcoital testing, and hysterosalpingography were normal in all cases. Basal serum hormone levels were measured before CC therapy (cycle days 3-5). Clinicians performed ultrasound-timed hCG administration on cycle days 16 and 17, and serum hormone determinations 1 week later. Treatment persisted for a maximum of 6 cycles.

Eighty-eight percent of PCOS patients receiving combined DEX-CC therapy ovulated, as determined by serum progesterone values, compared with 20% of PCOS patients receiving CC alone. Participants receiving DEX-CC therapy also demonstrated significant decreases in serum levels of LH, DHEAS, and testosterone, with a significant increase in serum progesterone concentrations. In addition, 40.5% and 4.2% of PCOS patients conceived while receiving CC with and without DEX, respectively. The authors conclude that the combination of DEX and CC in the treatment of CC-resistant anovulatory PCOS patients should be considered before gonadotropin therapy or surgical intervention.

Find this study

Parsanezhad EM, Alborzi S, Motazedian S, Omrani G. 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.

Who may be affected by these findings?

CC-resistant PCOS patients who have difficulty conceiving.

Expert commentary

This study confirms the previous observation that DEX therapy can increase the rate of ovulation and conception in CC-resistant anovulatory patients with normal serum DHEAS levels.1 While 88% of the PCOS patients receiving combined DEX-CC therapy in this study ovulated and had “regular ” menstrual cycles, the proportion of women resuming normal menstrual cyclicity on a monthly basis is not addressed. Using weekly serum progesterone measurements, the ratio of luteal phase weeks to total observed weeks (with a ratio of 0.5 denoting a 4-week ovulatory menstrual cycle)7 along with a description of menstrual cycle intervals (by days) would address this important question.

In addition, the authors do not discuss the proportion of patients who experienced side effects from intermittent DEX therapy or the rate of patient dropout over the study interval, leaving some practical aspects of this DEX administration unresolved. The authors do recommend that clinicians use combined DEX-CC therapy to treat CC-resistant anovulatory PCOS patients before gonadotropin therapy or surgical intervention, but this is not new. What is new, however, is how this recommendation fits with other advice regarding the use of insulin sensitizers in similar PCOS patients to reduce ovarian hyperandrogenism for ovulation induction.7,8 This issue is crucial because reversal of hyperinsulinemia in anovulatory PCOS women receiving insulin sensitizers may improve both ovulation and pregnancy outcome by ameliorating possible adverse effects of insulin excess on oocyte development.9,10

Bottom line

Future studies examining the safety, side effects, and efficacy of these agents will determine whether combined DEX-CC therapy for treating CC-resistant anovulatory PCOS patients may be a possible alternative to insulin sensitizers.

Dr. Dumesic reports no financial relationship with any companies whose products are mentioned in this article.

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