Hormone Therapy After Age 65 Linked to Increased Cancer and Stroke Risk
A study of over 83,000 women found that initiating hormone therapy after age 65 significantly increases risks for cancer and cerebrovascular events, reinforcing current guidelines that discourage starting systemic hormone therapy after age 60.
Initiation of menopausal hormone therapy (HT) after age 65 is linked to significantly increased risks for cancer and vascular events, according to a study published online Feb. 3 in Menopause. The analysis included 83,147 women aged 50 years and older in an Israeli health system during 2000-2022, of whom 6.6% initiated HT at ages 50-65 years and 1% initiated HT at age 65 or older.
The researchers found that HT use was associated with increased risks for several malignancies, including both hormone-sensitive and non-hormone-sensitive cancers. Initiation of HT at 65 years or older was associated with increased risks for any cancer (hazard ratio [HR], 2.216) and cerebrovascular accidents (HR, 2.695).
Among women initiating HT at 50 to 65 years, hazards were markedly elevated for cerebrovascular accidents (HR, 16.692), cancer (HR, 8.490), and ischemic heart disease/myocardial infarction (HR, 9.169) in an adjusted analysis. For women initiating HT at 50 to 65 years, prevalence was lower for ischemic heart disease/myocardial infarction (3.6 versus 9.2 percent) but higher for hypertension (11.0 versus 6.2 percent).
Study participants were divided by age of HT initiation: those who initiated HT at ages 50-65 years (n = 5500), those who initiated HT after age 50 and continued use beyond age 65 (n = 854), those who initiated HT at age 65 or older (n = 847), and those who never used HT (n = 75,946). Those who initiated at ages 50-65 and continued use beyond age 65 had significantly increased risks for cerebrovascular accidents (HR, 4.15, P < .001), cancer (HR, 1.36, P = .048), and ischemic heart disease or myocardial infarction (HR, 2.34, P < .001).
Nearly 40% of women in the 50-65 group continued therapy for over 10 years. Longer duration of therapy was associated with even greater morbidity risks.
The findings largely reinforce current guidelines, which discourage initiating systemic HT after age 60 or more than 10 years post-menopause. The significantly elevated risks of stroke and cancer observed in late initiators aged 65 and older provide strong empirical support for these cautious recommendations.
Although the crude analysis suggested that women who initiated HT at ages 50-65 had lower risks for both ischemic heart disease or myocardial infarction (3.6% vs 9.2% in never-users, P < .001) and cancer (19.2% vs 31.9%, P < .001), those lost significance after adjustment, indicating residual confounding in unadjusted comparisons.
The findings are limited by a lack of information about the formulation (including concomitant use of a progestogen), dose, and route of administration of hormone therapy used and subject to the usual limitations of an observational study. The study authors reinforce current recommendations for a personalized approach to hormone therapy use with regular reassessment of risks and benefits for women as they age.