Effects of Hormone Therapy on survival, cancer, cardiovascular and
dementia risks in 1.5 million women over age 65: a retrospective
observational study
Abstract
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.