VCU news

By Sathya Achia Abraham

Physicians may have a new drug to treat infertility in women with polycystic ovary syndrome, according to a national, multi-center clinical trial.

The cancer drug letrozole, which has been approved by the Food and Drug Administration to treat postmenopausal women with breast cancer, has been found to improve live birth and ovulation rates in infertile women with PCOS when compared head-to-head with gold-standard clomiphene.

The findings could change the current medical protocol for the treatment of fertility in women with PCOS.

The study, which was published last week in the New England Journal of Medicine, was led by researchers at Penn State College of Medicine and included 15 other medical institutions, including Virginia Commonwealth University.

Polycystic ovary syndrome, a leading cause of infertility, affects approximately 10 percent of women of reproductive age. PCOS is a disorder of the endocrine system that causes hormone imbalances and leads to irregular menstrual cycles.

For decades, clomiphene has been prescribed, but overall has poor efficacy, a relatively high multiple-pregnancy rate, and side effects that may include mood changes and hot flashes.

In the study, 750 women with PCOS were randomly assigned either letrozole or clomiphene, for up to five treatment cycles. The team found that the pregnancy rates were better with letrozole (28 percent) compared to clomiphene (19 percent).

“The study is significant – this is the study to change practice,” said lead investigator for the VCU-portion of the study Richard S. Lucidi, M.D., associate professor in the Department of Obstetrics and Gynecology in the VCU School of Medicine.

“If there is a better drug for treating fertility associated with PCOS, that’s important to know. Then we can change pregnancy rates and live birth rates in that population by switching to a different medication. … Physicians will switch from clomiphene to letrozole to treat infertility in women with PCOS,” he said.

Previously, research by other groups reported that letrozole works to treat infertility in women with PCOS, but, until this study, none had directly compared them head-to-head examining the live birth outcomes.

According to Lucidi, on the molecular level, clomiphene works by blocking the effects of estrogen and tricking the brain into thinking there is no estrogen around. This activity results in the production of follicle-stimulating hormone which stimulates the ovaries to trigger ovulation and release an egg.

Lucidi said letrozole has a slightly different mechanism of action and prevents the body from making estrogen.

“So instead of blocking the estrogen receptor, there really is no estrogen. But, the result is the same – the brain, in an attempt to get more estrogen made, makes FSH,” he said.

Further studies are needed to examine long-term outcomes of the offspring conceived while on letrozole.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; clinicaltrials.gov number NCT00719186.

To read more about the study: http://www.nejm.org/doi/full/10.1056/NEJMoa1313517

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