Menopausal Hormone Therapy Shows Persistent Bone Protection Despite Temporary Risk Increase After Discontinuation
核心洞察
A large-scale study of nearly 3 million women found that menopausal hormone therapy provides persistent bone protective effects even after treatment discontinuation.
Fracture risk temporarily increases for 1-10 years after stopping MHT, peaking around 3 years, before declining to levels lower than never-users.
Longer MHT treatment duration (5+ years) was associated with better long-term fracture protection compared to shorter treatment periods.
A comprehensive analysis of nearly 3 million women has revealed that menopausal hormone therapy (MHT) provides lasting bone protection that persists even after treatment discontinuation, despite a temporary period of increased fracture risk following cessation. The findings, published in The Lancet Healthy Longevity, offer new insights into the long-term skeletal benefits of hormone therapy.
Study Design and Population
Researchers from the University of Nottingham conducted a nested case-control study using U.K. primary and secondary care data from the Clinical Practice Research Datalink. The analysis compared 648,747 women who experienced their first fracture during the study period (January 1, 1998, to February 28, 2023) with 2,357,125 women with no fracture history. The average age of patients in the fracture cohort was 68.5 years, with a median MHT use duration of 3.6 years among cases and 3.9 years among controls.
Current Use Provides Strong Protection
The study demonstrated that current MHT use was associated with significantly reduced fracture risk compared with never-use. Women receiving estrogen-only therapy showed a 24% reduction in fracture risk (OR, 0.76; 95% CI, 0.74 to 0.78), while those on estrogen-progestogen combinations experienced a 25% reduction (OR, 0.75; 95% CI, 0.73 to 0.76).
Post-Discontinuation Risk Pattern
Following treatment cessation, a distinct pattern emerged. Fracture risk among former MHT users became elevated at 1 to 10 years after discontinuation, with estrogen-progestogen users showing a 6% increased risk (OR, 1.06; 95% CI, 1.05 to 1.08) compared to never-users. However, this temporary elevation reversed after 10 years, with fracture risk becoming lower than that of women who had never used MHT.
"Even after stopping MHT, women should benefit from notably reduced fracture risk in their later decades," said lead author Yana Vinogradova, PhD, of the Centre for Academic Primary Care in the University of Nottingham School of Medicine.
Duration-Dependent Benefits
The analysis revealed that treatment duration significantly influenced long-term outcomes. Women who used MHT for less than 5 years experienced an estimated 14 extra fracture cases per 10,000 women-years from 1 to 10 years following estrogen-progestogen treatment discontinuation. In contrast, those with 5 or more years of exposure had only 5 extra fracture cases per 10,000 women-years during the same period.
The protective effects were even more pronounced in the long term. Women with shorter treatment duration (less than 5 years) had 3 fewer fracture cases at more than 10 years following discontinuation, while those with longer exposure (5+ years) experienced 13 fewer fracture cases compared to never-users.
Clinical Implications
The findings have important implications for clinical decision-making regarding MHT use and discontinuation strategies. "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.
The researchers suggest that anticipating periods of increased risk might prompt clinicians to monitor bone health more closely at discontinuation, particularly for patients with additional fracture risk factors such as smoking or physical inactivity.
Risk Assessment Framework
The study's comprehensive analysis across different MHT formulations and treatment durations provides a framework for understanding fracture risk trajectories. While the pattern of initial protection followed by temporary elevation and eventual long-term benefit was consistent across all menopausal hormone treatments, risk levels varied based on specific MHT types and duration of 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 noted.
These findings may stimulate further clinical and biological research into hormone therapy mechanisms and optimal treatment strategies for maintaining bone health throughout the menopausal transition and beyond.