For millions of postmenopausal women managing chronic symptoms well into their sixties and beyond, the question of whether to continue or begin hormone therapy after 65 carries enormous practical weight — yet clinical guidance has remained stubbornly sparse for this age group. A large retrospective analysis now offers some of the most granular data yet on what actually happens to these women over time.
Drawing on records from 83,147 Israeli women enrolled in Clalit Health Services between 2000 and 2022, researchers stratified participants into four groups based on hormone therapy (HT) timing: never-users, initiators between ages 50 and 65, those starting at 65 or later, and women who began earlier but continued past 65. Using Cox proportional hazards models with age as the underlying timescale, the study tracked malignancies, cardiovascular events, osteoporosis, and dementia. Notably, HT use was associated with elevated risks for multiple malignancies — including both hormone-sensitive and non-hormone-sensitive cancers. In unadjusted analyses, women who initiated HT between 50 and 65 showed substantially lower rates of ischemic heart disease and myocardial infarction (3.6% vs. 9.2% in never-users) but higher hypertension prevalence (11.0% vs. 6.2%).
This study is significant precisely because it addresses a population that most landmark trials — including the Women's Health Initiative — either excluded or underrepresented. The cancer signal across hormone-sensitive and non-hormone-sensitive types is a finding that warrants scrutiny, as it suggests mechanisms beyond simple estrogen-receptor stimulation may be at play. That said, retrospective observational designs are inherently constrained: healthy-user bias, indication bias, and unmeasured confounders could substantially shift the adjusted estimates. The Israeli Clalit cohort is large and longitudinally tracked, lending reasonable statistical power, but generalizability to other ethnicities, healthcare systems, and HT formulations (oral vs. transdermal, estrogen-only vs. combined) remains uncertain. Overall, this is a confirmatory-plus-cautionary contribution — incrementally useful for individualized clinical conversations, but far from settling the debate on extended HT safety.