Effects of menopausal hormone therapy vary after age 65 years

Key takeaways:

• From 2007 to 2020, the number of U.S. women aged 65 years or older using hormone therapy decreased.
• Risks for mortality, certain cancers and cardiovascular outcomes varied by hormone therapy type.

Outcomes of using menopausal hormone therapy beyond age 65 years varied based on hormone therapy types, administration and strengths among women on Medicare, researchers reported in Menopause.

“Until recently, it was often thought that women do not need hormone therapy much after menopause because no serious menopausal symptoms persist in women aged 65 years or older,” Seo H. Baik, PhD, computational health research branch biostatistician at the Lister Hill National Center for Biomedical Communications at the National Library of Medicine within the NIH, and colleagues wrote. “However, studies reported that menopausal vasomotor symptoms persisted for 7 to 12 years in many women, and some vasomotor symptoms persisted in 42.1% of women aged 60 to 65 years, which suggests that not few numbers of women continue to suffer from vasomotor symptoms even after age 65 years.”

Baik and colleagues obtained prescription drug and encounter records from 10,944,328 women aged 65 years or older on Medicare from 2007 to 2020 from the CMS to evaluate the use of menopausal hormone therapy beyond age 65 years and possible health implications based on types of estrogen and progestogen, administration routes and dose strengths. Researchers evaluated the effects of different menopausal hormone therapy preparations on all-cause mortality; cancers such as breast, lung, endometrial, colorectal and ovarian; ischemic heart disease; heart failure; venous thromboembolism; stroke; atrial fibrillation; acute myocardial infarction; and dementia.

Overall, 14% of women ever used any hormone therapy during the study period. The proportion of women aged 65 years or older using any hormone therapy declined from 11.4% in 2007 to 5.5% in 2020.

Compared with never use or discontinuation of hormone therapy, overall estrogen monotherapy use beyond age 65 years was associated with significant risk reductions of:

• 19% for mortality (adjusted HR = 0.81; 95% CI, 0.79-0.82);
• 16% for breast cancer (aHR = 0.84; 95% CI, 0.83-0.86);
• 13% for lung cancer (aHR = 0.87; 95% CI, 0.84-0.9);
• 12% for colorectal cancer (aHR = 0.88; 95% CI, 0.84-0.91);
• 5% for congestive heart failure (aHR = 0.95; 95% CI, 0.94-0.96);
• 3% for venous thromboembolism (aHR = 0.97; 95% CI, 0.96-0.98);
• 4% for atrial fibrillation (aHR = 0.96; 95% CI, 0.95-0.98);
• 11% for acute myocardial infarction (aHR = 0.89; 95% CI, 0.87-0.92); and
• 2% for dementia (aHR = 0.98; 95% CI, 0.97-1).

Conjugated estrogen was associated with a 23% reduced breast cancer risk and estradiol was associated with a 12% reduced breast cancer risk. Most estrogen monotherapy types, routes and dose combinations were associated with an increased ischemic heart disease risk, with injectables associated with the highest increased risk of 17%. High-dose estrogen monotherapy was associated with an increased risk for stroke by 8% and increased risk for dementia by 3%.

Estrogen plus progestin combination therapy were associated with significant risk reductions of:

• 45% for endometrial cancer (aHR = 0.55; 95% CI, 0.5-0.6);
• 21% for ovarian cancer (aHR = 0.79; 95% CI, 0.71-0.89);
• 5% for ischemic heart disease (aHR = 0.95; 95% CI, 0.93-0.97);
• 5% for congestive heart failure (aHR = 0.95; 95% CI, 0.91-0.98); and
• 5% for venous thromboembolism (aHR = 0.95; 95% CI, 0.91-0.99).

Conversely, estrogen plus progesterone was associated with a risk reduction of 4% for congestive heart failure (aHR = 0.96; 95% CI, 0.92-1).

Estrogen plus progestogen therapy, regardless of progestogen type, had no significant association with mortality. Both estrogen plus progestin and estrogen plus progesterone combination therapies were associated with a 10% to 19% increased risk for breast cancer. However, risk was mitigated when using low-dose vaginal and transdermal estradiol plus progestin combination therapy.

Progesterone monotherapy was associated with a 22% reduced risk for mortality, a 10% reduced risk for breast cancer and a 19% reduced risk for lung cancer. Progestin monotherapy was associated with an 11% increased risk for mortality, a 21% increased risk for breast cancer and a 14% increased risk for lung cancer.

“Our findings offer important insights into the variations among different menopausal hormone therapies, which could assist in tailoring postmenopausal hormone therapy on an individual basis,” the researchers wrote.