Objectives: To examine the variation in patient’s health outcomes across different type, route, and strength of menopausal hormone therapy (HT). Design: Retrospective case-control study Setting: United States 2007-2020 Population: 10 million women aged 65 or more in US Medicare. Methods: Cox regression models with time-varying type, route, and strength of HT as well as patient characteristics. Main Outcome(s): all-cause mortality; 5 cancers- breast, lung, endometrial, colorectal, ovarian cancers; 6 CV conditions- ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, acute myocardial infarction; and dementia. Results Estrogen monotherapy (ET) exhibited a significant, 19% (HR=0.81; 95% CI 0.79-0.82), relative risk reduction on mortality. The reduction was greater with estradiol and vaginal/transdermal than conjugated estrogen and oral preparations. ET also exhibited significant risk reductions for all study cancers; breast (15%), lung (13%), endometrial (29%), colorectal (13%) and ovarian (14%). All ET preparations except low-dose slightly increased risk of ischemic heart diseases (1-4%). Both combination therapy and progestogen monotherapy exhibited significantly increased risk of breast cancer (7-14%). Oral ET exhibited moderately increased risk of stroke (6%) and dementia (2%). Conclusions: Among senior Medicare women, the effect of menopausal HT varies by type, route, and strength. The use of estradiol, vaginal/transdermal, and low/medium for menopausal care is safer than its counterparts.

Objectives: To examine the effects of estrogen on all-cause mortality, cancers, cardiovascular (CV) conditions, and dementia. Design: Retrospective observational study Setting: United States 2007-2018 Population: 1.5 million women aged over 65 in Medicare. Method: Cox regression with time-varying estrogen type, route, and strength as well as patient’s characteristics. Main Outcome(s): all-cause mortality; 5 cancers- breast, lung, endometrial, colorectal, ovarian cancers; 6 CV conditions- ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, acute myocardial infarction; and dementia. Results: Compared to counterparts, estrogen monotherapy (ET) exhibited a significant, 21% (HR=0.79; 95% CI 0.77-0.81), reduction in mortality risk. The reduction was greater with estradiol (HR=0.76; 95% CI 0.73-0.78) than conjugated estrogen (HR=0.83; 95% CI 0.80-0.86), and with topical (HR=0.69; 95% CI 0.66-0.71) than oral preparations (HR=0.86; 95% CI 0.83-0.89). ET also exhibited significant risk reductions for all study cancers, breast (HR=0.83; 95% CI 0.80-0.85), lung (HR=0.89; 95% CI 0.85-0.93), endometrial (HR=0.68; 95% CI 0.63-0.73), colorectal (HR=0.87; 95% CI 0.82-0.92) and ovarian (HR=0.86; 95% CI 0.80-0.92). Different dose levels exhibited similar risk reduction in mortality and cancers. ET slightly increased the overall CV risk, mostly risks of ischemic heart diseases and stroke. However, such risks occurred with CEE, oral, and high dose ET. Both combination therapy (HR=1.19; 95% CI 1.08-1.31) and progestogen monotherapy (HR=1.16; 95% CI 1.08-1.26) exhibited a significantly increased risk of breast cancer. No HT exhibited an increased risk of dementia. Conclusions: Among senior female Medicare beneficiaries, the effect of hormone therapy varies by type, route, and strength of estrogen.