Inguinal Hernia in men associated with increase in estrogen

According to a new study, Inguinal Hernia in men may be associated with an age-related increase in estrogen. The study has been published in the journal Proceedings of the National Academy of Sciences.

An inguinal hernia, one of the most common disorders that affect elderly men which often require corrective surgery. It occurs when an internal part of the body pushes through a weakness in the muscle or surrounding tissue wall. It can appear as a swelling or lump in the groin, or as an enlarged scrotum and may be painful.

The researchers 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 they reduced estrogen with a drug compound, it prevented the hernias, suggesting a therapy with preventive potential in humans.

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"It may make sense to treat at-risk men with an aromatase inhibitor that could decrease estrogen and strengthen the muscle," said Bulun, the lead author of the study.

Aromatase hormone converts a larger share of testosterone to estrogen. Bulun was investigating the effects of high estrogen in female mice as he initially focused on breast cancer and gynaecology,.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. But he noticed spotted large hernias developing in only the males.

Bulun 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.

"We realized the lower abdominal muscle is extraordinarily sensitive to estrogen," Bulun said. "Estrogen causes these fibroblasts to divide rapidly, at a much higher pace than the muscle cells."

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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 the potential for an aromatase inhibitor therapy that may be able to prevent surgery in at-risk patients.

“Those patients with greater risk of a hernia often have common factors like age or genetics, but overall the best predictor of a future inguinal hernia is a previous one, ”write the authors.

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. An inguinal hernia is a common malady in elderly men, and hernia repair is the most commonly performed general surgical procedure. Although its pathogenesis is poorly understood, the lifetime risk of an inguinal hernia is 27% in men and 3% in women.

For reference log on to https://doi.org/10.1073/pnas.1807765115