Study shows persistent bone protective effect of menopausal hormone therapy

Study shows persistent bone protective effect of menopausal hormone therapy | Image Credit: © tilialucida - © tilialucida - stock.adobe.com.

Recent findings published in Lancet Health Longevity point to persistent bone protective effects of menopausal hormone therapy (MHT) even after stopping treatment.¹

However, treatment discontinuation was associated with a medium-term elevation of fracture risk compared with never users, with data showing that bone fracture protection disappears completely at 1 year following treatment discontinuation. Fracture risk then peaks at about 3 years before declining again, falling to become similar to, and then lower than women who have never used MHT.

“Even after stopping MHT, women should benefit from notably reduced fracture risk in their later decades,” saidlead author Yana Vinogradova, PhD, of the Centre for Academic Primary Care in the University of Nottingham School of Medicine, UK, in a news release on the findings.²

For the study, the investigators compared data from 648,747 women who had a first fracture record during the study period (Jan 1, 1998, and Feb 28, 2023) with 2,357,125 women with no previous or contemporaneous fracture record. The average age of patients in the fracture cohort was 68.5 years (SD, 14). The median duration of MHT use was 3.6 years (IQR, 1.3 to 6.8) among cases and 3.9 years (IQR, 1.4 to 7.3) among controls.

Data showed that current use of MHT was associated with reduced fracture risk compared with never-use (estrogen-only, OR, 0.76; 95% CI, 0.74 to 0.78; estrogen–progestogen, OR, 0.75; 0.73 to 0.76). Fracture risk among MHT users then became higher at 1 to 10 years following treatment discontinuation (estrogen-only, OR, 0.99; 95% CI, 0.98 to 1.01; estrogen–progestogen, OR, 1.06; 95% CI, 1.05 to 1.08), but became lower at more than 10 years following cessation (estrogen-only, OR, 0.93; 95% CI, 0.91 to 0.94; estrogen–progestogen, OR, 0.95; 95% CI, 0.94 to 0.96).

This pattern was observed across all menopausal hormone treatments, although risk levels differed based on MHT types and the length of MHT use.

“The findings of our study confirmed that women on MHT show a progressively reducing fracture risk compared with women not using MHT. More importantly, we also observed a clear pattern of risk change after therapy was discontinued,”Vinogradova explained.²

Specifically, longer-term MHT use was associated with lower risk profiles than shorter use. Data showed that patients who had less than 5 years of MHT exposure had an estimated 14 extra fracture cases per 10,000 women-years from 1 to 10 years following estrogen–progestogen treatment. Comparatively, patients who had 5 or more years of MHT exposure had an estimated 5 extra fracture cases per 10,000 women-years from 1 to 10 years following treatment.

Similarly, patients who received estrogen–progestogen therapy for less than 5 years had an estimated 3 fewer fracture cases at more than 10 years following treatment discontinuation, compared with 13 fewer fracture cases for those with 5 or more years of MHT exposure.

According to the authors, these findings have important implications for patients and clinicians.

“Our comparative illustration of observed patterns of fracture risk for short and long use can help doctors and patients when discussing MHT treatment options, and to consider how fracture risk may change after stopping MHT use,” Vinogradova explained.² “Anticipating periods of increased risk might prompt doctors to check patients’ bone health at discontinuation, particularly for patients most at risk with other fracture risk factors such as smoking or inactivity. These novel findings may also usefully stimulate further clinical and biological research into these treatments.”

This article was published by our sister publication Urology Times.

REFERENCES

1. Discontinuation of menopausal hormone therapy and risk of fracture: nested case–control studies using routinely collected primary care data. The Lancet Healthy Longevity. 2025. doi:10.1016/j.lanhl.2025.1007

2. Stopping HRT leads to a period of higher risk of bone fracture for most women. News release. July 23, 2025. Accessed July 25, 2025. https://www.eurekalert.org/news-releases/1092022