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DRUG INFORMATION ROUNDS

Aromatase Inhibitors for Ovulation and Pregnancy in Polycystic Ovary Syndrome

Pharmacy Practice Resident, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, Richmond

Denise R Kockler, PharmD BCPS

Director, Drug Information Services, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals; Associate Clinical Professor, School of Pharmacy, Virginia Commonwealth University

Reprints: Dr. Kockler, Drug Information Services, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals, 401 N. 12th St., PO Box 980042, Richmond, VA 23298, fax 804/628-3919, dkockler{at}mcvh-vcu.edu

OBJECTIVE: To evaluate evidence for use of aromatase inhibitors for ovulation induction and pregnancy in patients with polycystic ovary syndrome (PCOS).

DATA SOURCES: A MEDLINE search (1966-May 2009) was conducted using the search terms anastrozole, aromatase inhibitors, exemestane, letrozole, ovulation, and polycystic ovary syndrome to identify relevant studies.

STUDY SELECTION AND DATA EXTRACTION: Prospective clinical trials published in English and conducted in humans were identified. Trials using intrauterine insemination methods for pregnancy were excluded. The resulting articles were separated into 2 groups: aromatase inhibitor use in clomiphene-resistant patients and use in treatment-naïve patients. Eleven trials were reviewed.

DATA SYNTHESIS: Accepted pharmacologic treatments for women with PCOS and infertility include clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone (GnRH) analogs. Each medication has variable efficacy rates and adverse effects. Therefore, other treatments are needed for a subset of women with PCOS and infertility. Evidence suggests that nonsteroidal aromatase inhibitors, specifically letrozole and anastrozole, may have ovulation-inducing effects by inhibiting androgen-to-estrogen conversion. Select trials with aromatase inhibitors have demonstrated efficacy for increased endometrium thickness, ovulation rates, and pregnancy rates when used in clomiphene citrate-resistant or treatment-naïve patients.

CONCLUSIONS: Further trials comparing aromatase inhibitors with clomiphene citrate are necessary before aromatase inhibitors can be recommended routinely for ovulation induction in women with PCOS and infertility. However, aromatase inhibitors may be considered in a subset of this population, specifically women who are clomiphene citrate resistant or those who, after discussion of risks and benefits, are not candidates for clomiphene citrate, gonadotropins, or GnRH analogs.

Key Words: anastrozole, aromatase inhibitors, exemestane, letrozole, ovulation, polycystic ovary syndrome

Published Online, July 7, 2009. www.theannals.com, DOI 10.1345/aph.1M096