A landmark Danish cohort study tracking over 800,000 women has provided compelling evidence dispelling longstanding concerns about the safety of menopausal hormone therapy (MHT), commonly referred to as hormone replacement therapy (HRT), particularly regarding long-term mortality risk. Published recently in The BMJ, this extensive register-based investigation reveals that MHT does not increase the likelihood of death from any cause, offering new clarity and reassurance to clinicians and women navigating menopausal health management amid ongoing controversy about treatment safety.
Hormone therapy remains the most effective intervention for alleviating a constellation of distressing menopausal symptoms such as vasomotor instability marked by hot flashes, sleep disruption, mood variability, and depressive episodes. Despite its proven symptom control, fear of adverse effects, fueled partially by earlier studies that linked HRT to cardiovascular and oncologic risks, has led to a marked decrease in its utilization over the past two decades. This new Danish research leverages robust real-world data to address vital gaps in understanding the long-term mortality consequences of MHT.
Utilizing the comprehensive national health registers of Denmark, researchers identified women born between 1950 and 1977 who were alive at age 45, excluding those with previous hormone therapy use, bilateral oophorectomy, or histories of conditions known to contraindicate hormonal treatment, including thromboembolic diseases and estrogen-sensitive cancers. This meticulous selection ensured a homogenous study population in which the pure effects of MHT on survival could be observed without confounding from prior treatment or high-risk medical conditions.
Spanning a median follow-up period exceeding 14 years, the observational cohort included 876,805 women, among whom nearly 12% initiated menopausal hormone therapy prescriptions. Deaths were recorded in over 47,000 participants—5.4% of the cohort—providing a substantial dataset for mortality analysis across various subgroups. Adjustments were made for an array of influential variables such as age at initiation, parity, socioeconomic indicators like education and income level, country of origin, and underlying comorbidities including diabetes mellitus, hypertension, and cardiovascular disease, to enhance the validity of findings.
Initial unadjusted mortality rates indicated a higher incidence among women with current or past MHT use compared to never-users. Specifically, 54.9 deaths versus 35.5 deaths per 10,000 person-years were observed, potentially reflecting confounding by indication or selection bias. However, once the multivariate adjustments for influential demographic and clinical factors were accounted for, no statistically significant difference in all-cause mortality emerged between hormone therapy users and non-users. This suggests that underlying health conditions or socioeconomic factors, rather than hormone therapy itself, may explain any observed mortality differences.
Importantly, the study delved into the impact of hormone therapy duration on survival outcomes. Long-term use, defined as spanning a decade or more—which was reported by a small subset of participants (0.8%)—also demonstrated no excess mortality risk. This is a critical observation, as concerns about cumulative HRT exposure contributing to adverse outcomes have often constrained treatment duration in clinical practice. The data therefore provide evidence supporting the safety of both short- and long-term menopausal hormone therapy.
Exploring cause-specific mortality, analyses did not identify robust differences in deaths attributed to cardiovascular disease, cerebrovascular events such as stroke, or malignant neoplasms including breast, uterine, and ovarian cancers. This comprehensive cause-specific mortality assessment underscores the neutrality of menopausal hormone therapy with respect to these clinically significant endpoints, further consolidating its safety profile.
A particularly noteworthy finding emerged in the subgroup of women who underwent bilateral oophorectomy—the surgical removal of both ovaries—between ages 45 and 54 for benign indications. In this group, menopausal hormone therapy conferred a marked survival advantage, with risk reductions ranging from 27% to 34% compared to non-users within the same demographic. This survival benefit highlights the potential protective effect of replacing lost endogenous estrogen in surgically menopausal women and prompts renewed consideration of routine hormone therapy in this high-risk population.
Moreover, the study offers preliminary insights into delivery modality differences of MHT. Use of transdermal formulations, including patches and gels, was tentatively associated with a slightly improved survival outlook in comparison to untreated women. Although encouraging, the authors urge caution in interpreting this finding, advocating for confirmatory research before integrating delivery route preferences decisively into clinical decision-making frameworks.
As an observational investigation, the study cannot definitively establish causal relationships, and residual confounding or unmeasured variables could influence outcomes. The authors acknowledge inherent limitations, including potential selection biases and confounders typical of registry-based data. Nevertheless, the study benefits from an extraordinarily large sample size, near-complete national follow-up, and rigorous statistical adjustments, bolstering the reliability and generalizability of its conclusions.
Importantly, this research was conducted in compliance with the Declaration of Helsinki, utilizing national registers with permission from Danish health authorities. The analyses adhered to STROBE guidelines for cohort studies and were performed using up-to-date statistical software packages, enhancing transparency and methodological soundness.
In summary, this comprehensive nationwide cohort study delivers an impactful message: menopausal hormone therapy, when prescribed appropriately, does not increase mortality risk in women undergoing natural menopause. It offers additional evidence negating causative links to cardiovascular or cancer-specific deaths, alleviating concerns that have historically curtailed hormone therapy use. The demonstrated survival benefit in surgically menopausal women further underscores the therapy’s clinical value in tailored patient management.
This work paves the way for reintroducing menopausal hormone therapy confidently within clinical practice, aligning with current guidelines advocating HRT in women experiencing moderate to severe menopausal symptoms without contraindications. Furthermore, the findings warrant deeper exploration of MHT use post-bilateral oophorectomy to optimize outcomes in this vulnerable subset.
As millions of women worldwide grapple with menopausal changes, these findings inject renewed optimism in leveraging hormone therapy safely and effectively. The research reinvigorates the conversation about individualized, evidence-based menopausal care that balances symptomatic relief against safety—a critical stride toward enhancing women’s health and quality of life during midlife transitions.
Subject of Research: People
Article Title: Menopausal hormone therapy and long term mortality: nationwide, register based cohort study
News Publication Date: 18-Feb-2026
Web References: https://doi.org/10.1136/bmj-2025-085998
Keywords: Menopause, Hormone therapy, Medical treatments
