Menopausal Hormone Therapy Not Linked to Increased Mortality Risk

A nationwide cohort study published in The BMJ on February 18, 2026, found that menopausal hormone therapy (MHT) is not associated with an increased risk of death. The findings support existing medical guidelines that recommend hormone therapy for women who have recently entered menopause and experience moderate to severe symptoms, provided they have no contraindications.

The research comes at a time when the use of MHT, also known as hormone replacement therapy (HRT), has steadily declined over the last two decades. This decline has been driven primarily by safety concerns, while real-world evidence regarding the therapy’s effect on overall mortality has remained limited.

Study Design and Participant Cohort

Researchers led by Anders Pretzmann Mikkelsen, MD, from Copenhagen University Hospital Herlev in Denmark, utilized nationwide Danish registers to track the health outcomes of a large group of women. The study included 876,805 women born between 1950 and 1977 who were alive at age 45.

To ensure the accuracy of the results, the researchers excluded women with specific medical histories, including liver disease, a history of blood clots, or cancers of the womb, ovaries, or breasts. Women who had previously used menopausal hormone therapy or those who had undergone surgery to remove both ovaries (bilateral oophorectomy) were also excluded from the main analysis.

The follow-up period for each participant began on their 45th birthday and concluded on July 31, 2023, resulting in a median follow-up duration of 14.3 years. The analysis accounted for several potentially influential factors, such as income, education, country of birth, number of children, age, and underlying health conditions including heart disease, high blood pressure, and diabetes.

Mortality Findings and Hazard Ratios

Of the women included in the main analysis, 104,086 (11.9%) redeemed a prescription for menopausal hormone therapy. During the follow-up period, 47,594 (5.4%) of the total participants died.

The study found that the incidence rate of death was 35.5 deaths per 10,000 person-years for women who used MHT, compared to 54.9 deaths per 10,000 person-years for those who were unexposed. The adjusted hazard ratio was 0.96, with a 95% confidence interval of 0.93 to 0.98.

The researchers further analyzed mortality based on the cumulative duration of MHT use. The adjusted hazard ratios were as follows:

• Less than 1.0 year of use: 1.01 (0.98 to 1.05)
• 1.0 to 2.9 years of use: 0.94 (0.89 to 0.98)
• 3.0 to 4.9 years of use: 0.90 (0.84 to 0.95)
• 5.0 to 9.9 years of use: 0.89 (0.84 to 0.95)
• 10 years or more of use: 0.98 (0.90 to 1.07)

Impact on Bilateral Oophorectomy Patients

The study also examined a specific subgroup of 703 women who underwent bilateral oophorectomy between the ages of 45 and 54. Among this group, those who used menopausal hormone therapy experienced a 27% to 34% lower mortality hazard than those who did not.

The data showed a notable difference in the median age at death for this subgroup, with MHT users having a median age at death of 60.9 years, compared to 56.6 years for those not using the therapy.

The magnitude of survival difference found in our study should prompt further discussion as to whether more women should be offered systemic menopausal hormone therapy after undergoing bilateral oophorectomy

Anders Pretzmann Mikkelsen and colleagues

Clinical Context and Application

MHT is used to treat a variety of menopausal symptoms, including depression, mood swings, sleep disturbance, and hot flashes. Despite its efficacy in relieving these symptoms, safety concerns have led to a decrease in prescriptions over the last 20 years.

The results of this Danish study align with current guidelines that recommend the use of hormone therapy for women who have recently begun menopause and suffer from moderate to severe symptoms, provided there are no contraindications to the treatment.