Aromatase Inhibitors: Potential Reproductive Implications

A year ago, I found and posted some old research articles about aromatase and endometriosis. In the first article, dated May 2004, it reads, “Aromatase P450 (P450arom) is the key enzyme for biosynthesis of estrogen, which is an essential hormone for the establishment and growth of endometriosis. There is no detectable aromatase enzyme activity in normal endometrium; therefore, estrogen is not locally produced in endometrium. Endometriosis tissue, however, contains very high levels of aromatase enzyme, which leads to production of significant quantities of estrogen. Moreover, one of the best-known mediators of inflammation and pain, prostaglandin E2, strikingly induces aromatase enzyme activity and formation of local estrogen in this tissue. Additionally, estrogen itself stimulates cyclo-oxygenase-2 and therefore increases the formation of prostaglandin E2 in endometriosis. We were able to target this positive feedback cycle in endometriosis using aromatase inhibitors. In fact, pilot trials showed that aromatase inhibitors could decrease pelvic pain associated with endometriosis“.

In the second article, dated August 2007, researchers confirmed that “molecular alterations such as the presence of aromatase in endometriotic tissues could be involved in the development or maintenance of endometriosis.”

In the third article, dated January 2009, Dr. Serdar Bulun, George H. Gardner Professor of Clinical Gynecology at Northwestern University’s Feinberg School of Medicine said, ““We came up with a new treatment of choice for post-menopausal women with endometriosis,” Bulun said. Moreover, treatment with an aromatase inhibitor is a very good option for premenopausal women with endometriosis not responding to existing treatments, he said“.

Now, it seems people are rethinking that avenue…

Aromatase Inhibitors: Potential Reproductive Implications
Mohamed A. Bedaiwy, MD, PhD, Noha A. Mousa, MD, Robert F. Casper, MD
Received 10 March 2009; accepted 12 May 2009. published online 16 July 2009.

Abstract
MEDLINE, EMBASE, Scopus, and Web of Science databases literature search from inception to March 2009 was performed to identify published clinical trials and cohort, observational, and in vitro studies that evaluated the use of aromatase inhibitors in reproductive medicine for indications other than ovulation induction. Aromatase inhibitors are currently being investigated for breast cancer prevention in women at high risk. Aromatase inhibitors may be used for treatment of symptomatic myomas and endometriosis as an alternative to surgical intervention. Current evidence does not support the routine use of aromatase inhibitors for these conditions without prospective controlled trials. Aromatase inhibitor cotreatment can be used to prevent the initial estrogen flare effect of gonadotropin-releasing hormone agonist treatment to offer flexibility in initiating this therapy.