Early Surgical Menopause and HRT Linked to Increased Long-Term Risk of Cholecystectomy in Women: Study

The use of hormone replacement therapy (HRT) further elevated the risk, particularly in women who underwent surgical menopause and began HRT before menopause, with a hazard ratio of 2.28. Early surgical menopause and HRT use were independently identified as contributors to the increased risk of cholecystectomy. The findings were published online in Frontiers in Medicine on November 27, 2024.

Women have a higher risk of gallbladder disease compared to men, indicating a potential influence of female hormones in its development. For this purpose, Guan-Jun Ding, The Second Department of General Surgery, Ningbo No. 9 Hospital, Ningbo, China, and colleagues aimed to evaluate menopausal characteristics, hormone replacement therapy, and their combined impact on women's long-term risk of cholecystectomy.

The study included 184,677 women from the UK Biobank. Multivariable Cox regression models were employed to analyze the associations between menopausal characteristics, HRT, and the risk of cholecystectomy. Additionally, the combined effects of HRT use, menopausal status, and menopause type on the incidence of cholecystectomy were assessed.

The study led to the following findings:

• Over a median follow-up of 12.7 years, 4,991 cholecystectomy cases were reported.
• Natural menopause, regardless of the age at onset, was not linked to an increased risk of cholecystectomy.
• Surgical menopause at a young age was associated with a higher risk of cholecystectomy.
• Ever using hormone replacement therapy was associated with an elevated risk of cholecystectomy.
• The highest risk was observed in women who underwent surgical menopause and started HRT before menopause, with a hazard ratio of 2.28, compared to naturally menopausal women who never used HRT.

The study's limitations include potential residual confounding and recall bias from self-reported data on menopause and HRT use. The prospective design likely reduces differential misclassification, but the lack of data on HRT formulations limits further analysis. The researchers focused on cholecystectomy without assessing broader gallbladder disease risk. Additionally, the study population, predominantly white, middle-aged, and older UK women, limits the generalizability of results to other groups.

"Surgical menopause at a young age, rather than natural menopause, was linked to a higher risk of cholecystectomy. Independent of menopausal characteristics, HRT use increased this risk, particularly in surgically menopausal women initiating HRT before menopause," the researchers concluded.

Reference:

Ding, G., Jiang, W., Lyu, J., Ma, J., Chen, G., Li, F., Yang, S., Miao, M., & Hua, Y. (2024). Menopausal characteristics and hormone replacement therapy about long-term risk of cholecystectomy in women. Frontiers in Medicine, 11, 1446271. https://doi.org/10.3389/fmed.2024.1446271