Health outcomes of hormone therapy initiated or continued after age 65

Menopausal hormone therapy (HT) is effective for alleviating vasomotor symptoms but remains controversial regarding long-term safety, particularly in women over 65. Despite guidelines recommending initiation before age 60, a notable proportion of older women continue or begin HT later in life. The health outcomes of HT in women aged 65 and older, especially those initiating therapy after 65, compared with younger users and nonusers were evaluated.

This retrospective cohort study included 83,147 women aged 50 years or older enrolled in Clalit Health Services (2000-2022). Women were categorized by age at HT initiation: never-users, initiators at 50-65 years, initiators 65 years or older, or initiators after 50 continuing beyond 65. Outcomes included malignancies, cardiovascular events, osteoporosis, and dementia. Group differences were evaluated using χ 2 tests, and time-to-event associations were examined using Cox proportional hazards models with age as the underlying time scale. To evaluate the health outcomes of HT in women aged 65 and older, especially those initiating therapy after 65, compared with younger users and nonusers.

HT use was associated with increased risks of several malignancies, including both hormone-sensitive and non-hormone-sensitive cancers. In crude analyses, women initiating HT at 50-65 years had lower ischemic heart disease/myocardial infarction prevalence (3.6% vs. 9.2%) but higher hypertension (11.0% vs. 6.2%). In adjusted Cox models, initiation at 65 years or older was associated with increased hazards of any cancer (hazard ratio [HR]: 2.216, 95% confidence interval [CI]: 1.833-2.677) and cerebrovascular accident (HR: 2.695, 95% CI: 2.358-3.079). Among women initiating HT at 50-65 years, hazards were markedly elevated for cerebrovascular accident (HR: 16.692, 95% CI: 15.571-17.893), cancer (HR: 8.490, 95% CI: 7.281-9.900), and ischemic heart disease/myocardial infarction (HR: 9.169, 95% CI: 8.321-10.102); the crude cardiovascular advantage was not observed after adjustment.

Initiation of HT after age 65 is linked to significantly increased risks of cancer and vascular events, supporting current guidelines discouraging late initiation. While HT may offer some cardiovascular benefits when started earlier, use in older women should involve individualized risk-benefit assessment and close monitoring. These findings underscore the need to align clinical practice with evolving evidence and guideline recommendations. Given the retrospective design, incomplete pre-2000 medical history, and potential residual confounding, findings should be interpreted with caution.