An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery. The study, led by Dr. Serdar Bulun, chair and the John J. Sciarra Professor of Obstetrics and Gynecology at Northwestern University Feinberg School of Medicine, found the lower abdominal muscles of mouse models are particularly sensitive to estrogen, developing scar tissue in response to increases in estrogen levels that weakens the abdominal wall and eventually causes a hernia.

When the investigators reduced estrogen with a drug compound, it prevented the hernias, suggesting a therapy with preventive potential in humans. It may make sense to treat at-risk men with an aromatase inhibitor that could decrease estrogen and strengthen the muscle. Inguinal hernias occur when tissue, such as the intestines, protrudes through the inguinal canal, a weak spot near the groin in the human abdominal wall.

These hernias are the most common reason men undergo surgery. There are more than 700,000 inguinal hernia repair surgeries performed each year in the United States, according to the Food and Drug Administration. While the chances of an inguinal hernia increase as men age, the root cause remains unknown. One other consequence of aging in men is that a larger share of testosterone is converted to estrogen by a hormone called aromatase.

Researchers was investigating the effects of high estrogen in female mice. One experiment involved boosting estrogen levels by incorporating the human aromatase gene into the mouse genome, creating mice who would convert testosterone into estrogen throughout the body.

Researcher investigated these mice, finding large swaths of fibroblasts — scar tissue — developing in a small muscular sphincter, a structure analogous to the inguinal canal in humans. He discovered that the lower abdominal muscle is extraordinarily sensitive to estrogen. Estrogen causes these fibroblasts to divide rapidly, at a much higher pace than the muscle cells.

The proliferation of the fibroblasts weakens the integrity of the sphincter and it eventually gives way, causing a hernia. When the investigators gave the mice a drug that blocked aromatase, and therefore the conversion of testosterone to estrogen, the hernias stopped, pointing toward estrogen as the cause and indicating potential for an aromatase inhibitor therapy that may be able to prevent surgery in at-risk patients.
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