Menopausal hormone therapy remains one of the most debated interventions in women’s health. Since the early 2000s, clinicians have navigated evolving evidence on cardiovascular risk, breast cancer, thromboembolism, and overall survival. A new nationwide cohort study published in The BMJ provides important real world data on long term mortality associated with menopausal hormone therapy in a large contemporary population.
This blog reviews the findings of the study titled Menopausal hormone therapy and long term mortality: nationwide, register based cohort study published in The BMJ (2026;392:e085998), and discusses their implications for evidence based clinical decision making.
Most women enter menopause between 45 and 55 years of age. Vasomotor symptoms, sleep disturbance, genitourinary syndrome of menopause, cognitive complaints, and mood changes affect up to 80 percent of women, with many experiencing symptoms for more than seven years. For a substantial proportion, symptoms are severe enough to impair occupational functioning and quality of life.
Despite the well documented efficacy of oestrogen containing regimens for symptom control, prescribing patterns changed dramatically after the 2002 publication of the Women's Health Initiative trial results. That study reported increased risks of breast cancer, stroke, venous thromboembolism, and coronary heart disease among older postmenopausal women receiving combined conjugated equine oestrogen and medroxyprogesterone acetate.
However, important contextual issues were raised:
Since then, clinicians have grappled with reconciling symptom control benefits with long term safety concerns. All cause mortality represents a clinically meaningful endpoint because it integrates competing risks and avoids disease specific attribution bias.
This study used linked Danish nationwide registries to evaluate mortality outcomes in women born between 1950 and 1977 who were alive at age 45. Follow up began at each woman’s 45th birthday and continued until 31 July 2023.
After exclusions for contraindications, prior menopausal hormone therapy use, and bilateral oophorectomy before age 45, 876,805 women were included.
Key features:
Systemic therapy included combined oestrogen and progestogen regimens and oestrogen monotherapy. Low dose vaginal oestrogens were excluded due to negligible systemic absorption.
A total of 47,594 deaths occurred during follow up.
Crude incidence rates:
After adjustment for age, calendar period, parity, socioeconomic variables, cardiovascular comorbidities, diabetes, hypercholesterolaemia, and hospital contact burden:
Adjusted hazard ratio for all cause mortality: 0.96 (95 percent CI 0.93 to 0.98)
Menopausal hormone therapy was not associated with increased mortality. If anything, a modest reduction was observed.
When stratified by cumulative duration:
No duration category showed increased mortality. Intermediate durations were associated with modest reductions.
From a clinical perspective, these findings challenge the persistent assumption that longer duration necessarily confers increased overall mortality risk.
Deaths were classified as:
The study did not find unequivocal differences in cardiovascular or cancer specific mortality between users and non users.
Short term use under five years showed:
However, these differences were not consistent or amplified with longer use.
Clinically, this suggests no strong signal of excess cause specific mortality attributable to systemic therapy within the observed follow up window.
Among women who underwent bilateral oophorectomy between ages 45 and 54, menopausal hormone therapy was associated with a 27 to 34 percent reduction in mortality hazard.
Median age at death:
This aligns with prior observational evidence suggesting premature oestrogen deprivation may increase long term morbidity and mortality if untreated.
Current guidance from the Royal College of Obstetricians and Gynaecologists recommends offering hormone therapy to women undergoing premenopausal bilateral oophorectomy until the average age of natural menopause.
These Danish data strengthen the biological plausibility and survival benefit of systemic therapy in surgically menopausal women.
Stratified analyses suggested:
These subgroup findings should be interpreted cautiously due to potential residual confounding and multiple comparisons.
However, they contribute to ongoing discussions regarding thrombotic risk and first pass hepatic metabolism differences between oral and transdermal formulations.
Three additional approaches tested robustness:
Results were materially unchanged. The as treated model showed a stronger mortality reduction, although this may reflect healthy user bias.
The registry design minimises recall bias and loss to follow up.
It remains possible that very late adverse effects beyond age 70 may not yet be detectable.
This study adds to accumulating evidence that:
For clinicians counselling symptomatic perimenopausal and early postmenopausal women without contraindications, these data provide reassurance.
Importantly, the results align closely with extended follow up from the Women's Health Initiative, which also showed neutral long term mortality.
The narrative that menopausal hormone therapy shortens lifespan is not supported by contemporary large scale data.
When discussing therapy, clinicians should consider:
Mortality risk alone should not be a barrier to appropriate therapy in eligible women.
In this large Danish nationwide cohort study published in The BMJ, systemic menopausal hormone therapy was not associated with increased long term mortality. Women with bilateral oophorectomy between 45 and 54 years experienced a substantial survival benefit with therapy.
For healthcare professionals, these findings reinforce guideline supported prescribing of menopausal hormone therapy for symptomatic women without contraindications, particularly those with surgical menopause.
Ongoing research should explore optimal formulation, timing, and duration strategies, and evaluate outcomes into later decades of life.
Mikkelsen AP, Bergholt T, Lidegaard Ø, Scheller NM. Menopausal hormone therapy and long term mortality: nationwide, register based cohort study. The BMJ. 2026;392:e085998. doi:10.1136/bmj-2025-085998
This blog is intended for healthcare professionals for educational purposes only. It summarises findings from a peer reviewed observational study and does not replace individual clinical judgement. Treatment decisions should be based on comprehensive patient assessment, current clinical guidelines, and shared decision making.
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