More Research Is Needed on Aromatase Inhibitors in PCOS


PHILADELPHIA — The jury is still out on whether aromatase inhibitors could offer an alternative to clomiphene in the treatment of infertility associated with polycystic ovary syndrome, based on results in two small clinical trials.

Aromatase inhibitors are on the horizon, Dr. Andrea D. Coviello said at Endocrinology in the News, sponsored by Boston University, INTERNAL MEDICINE NEWS, and FAMILY PRACTICE NEWS. Although they have been approved for use in breast cancer, they are still experimental for ovulation induction. Instead of blocking the receptors centrally in the hypothalamus and the pituitary, aromatase inhibitors completely block estradiol production. Like clomiphene, aromatase inhibitor drugs are used during the follicular phase, she said.

The rationale for moving to aromatase inhibitors is that this class of drugs is thought to have fewer antiestrogenic side effects, including a lower risk of ovarian hyperstimulation syndrome and a lower risk of multiple gestation. But there are also significant concerns about fetal development problems in the babies conceived by women who were using aromatase inhibitors, explained Dr. Coviello, of the Endocrinology, Diabetes, and Nutrition Section, Boston University School of Medicine.

A definitive study that would help physicians assess how aromatase inhibitors stack up to clomiphene has yet to be done. The available data are derived from very small studies, she noted.

In a prospective, randomized trial of 74 patients, researchers did not find a significant difference in pregnancy rates between women who received clomiphene and those who received the aromatase inhibitor letrozole (Fertil. Steril. 2006;86:1447–51). However, the researchers found significantly lower estrogen levels in the letrozole group on the day of human chorionic gonadotropin administration, Dr. Coviello said.

Another study, published online, compared the efficacy of letrozole and clomiphene among women who had failed to ovulate when taking 100 mg/day of clomiphene citrate (Fertil. Steril. 2008 January [Epubdoi:10.1016/j.fertnstert.2007.08.044]). Sixty-four patients were randomized to receive either 7.5 mg/day of letrozole or 150 mg/day of clomiphene. The researchers found that letrozole had better ovulation and pregnancy rates compared with clomiphene. However, those results came as no surprise because the women in the study were clomiphene resistant, Dr. Coviello said. So although it showed that letrozole is not inferior in terms of ovulation, it failed to make the case that aromatase inhibitors outperform clomiphene.

Dr. Coviello stated she had no financial conflicts of interest to disclose. INTERNAL MEDICINE NEWS, FAMILY PRACTICE NEWS, and this newspaper are published by the International Medical News Group, a division of Elsevier.

Next Article: