Initiation of Menopausal Hormone therapy later in life tied to adverse cardiovascular outcomes: Study

Menopausal HT is still one of the most effective treatments for vasomotor symptoms such as hot flashes and night sweats, but its long-term safety profile is still controversial, especially in women over 65 years of age. The analysis included 83,147 women aged 50 years or older who were enrolled in Clalit Health Services between 2000 and 2022. Women were divided into four groups according to age at HT initiation: never-users, initiators between 50 and 65 years of age, initiators at 65 years or older, and women who initiated therapy after age 50 and continued use beyond 65 years of age. The main outcomes of interest were malignancies, cardiovascular events, osteoporosis, and dementia.

Comparisons between baseline groups were conducted by chi-square tests, and associations between time-to-events were investigated by Cox proportional hazard models with age as the underlying timescale. The main objective was to evaluate the health outcomes in women aged 65 years or older who initiated HT after the age of 65, compared with younger women.

Key findings

• During the study period, the use of HT was found to be significantly associated with an increased risk of various malignancies, including both hormone-sensitive and non–hormone-sensitive cancers.

• In the crude analysis, women who started HT between 50 and 65 years of age had a lower prevalence of ischemic heart disease or myocardial infarction than never-users, at 3.6% and 9.2%, respectively.

• However, these women also had a higher prevalence of hypertension, at 11.0% compared with 6.2% in never-users.

• Adjusted Cox proportional hazards models showed that women who initiated HT at 65 years or older had a significantly increased risk of adverse outcomes.

• The hazard ratio for any cancer was 2.216, with a 95% confidence interval of 1.833 to 2.677.

• The hazard ratio for cerebrovascular accident was 2.695, with a 95% confidence interval of 2.358 to 3.079.

• The hazard ratio for cerebrovascular accident was 16.692 (95% confidence interval 15.571 to 17.893), for cancer was 8.490 (95% confidence interval 7.281 to 9.900), and for ischemic heart disease or myocardial infarction was 9.169 (95% confidence interval 8.321 to 10.102).

The onset of menopausal hormone therapy at or after the age of 65 years is linked to a significantly higher risk of cancer and cerebrovascular events, consistent with current recommendations against late initiation. Although HT can alleviate symptoms and has been considered to potentially offer cardiovascular benefits, the adjusted results in this large database underscore the importance of individualized risk-benefit assessment.

Reference:

Carney, Alon MD1,2; Gluzman, Milana MD2; Kolushev-Ivshin, Ilona MPH2; Amar, Shimon MD1,2. Health outcomes of hormone therapy initiated or continued after age 65. Menopause ():10.1097/GME.0000000000002721, February 3, 2026. | DOI: 10.1097/GME.0000000000002721