Differential Effects of Type, Route and Dose of Menopausal Hormone
Therapy on survival, cancer, cardiovascular and dementia risks in 10
million women age over 65: a retrospective case-control study
Abstract
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.