Abstract
Nearly two decades have passed since the release of Women's Health Initiative (WHI) postmenopausal hormone therapy trial findings, yet the medical community, and general public remain unsettled by ongoing debate over the benefits and safety of sex hormone replacement therapy (HRT). Among the contentious issues is the elevated risk of venous thromboembolism (VTE) and stroke observed in HRT users (1). While major guidelines rightly recommend the use of transdermal estradiol in women with risk factors, little attention has been given to the potential impact of the type of estrogen molecule. This review aims to highlight the importance of selecting appropriate estrogen therapy to enhance safety.
Highlights
Two decades have passed since the release of Women’s Health Initiative (WHI) postmenopausal hormone therapy trial findings, yet the medical community, and general public remain unsettled by ongoing debate over the benefits and safety of sex hormone replacement therapy (HRT)
Among the contentious issues is the elevated risk of venous thromboembolism (VTE) and stroke observed in HRT users [1]
In a population-based, case-control study of ∼400 postmenopausal women aged 30–79 years using oral hormone therapy, conjugated equine estrogen (CEE) use was significantly associated with increased venous thrombosis risk and a trend toward increased myocardial infarction (MI) risk when compared with E2 [15]
Summary
Two decades have passed since the release of Women’s Health Initiative (WHI) postmenopausal hormone therapy trial findings, yet the medical community, and general public remain unsettled by ongoing debate over the benefits and safety of sex hormone replacement therapy (HRT). Prior to the landmark WHI trial, several large-scale observational studies were in favor of HRT’s protective effects, as treated women were found to be at lower risk of CHD and mortality [6] To substantiate these observations, WHI postmenopausal hormone trials set out to investigate HRT in women aged 50–79 years; participants randomized to intervention arms received either conjugated equine estrogen (CEE) 0.625 mg alone (absent uterus) or with cyclical medroxyprogesterone acetate (MPA) 2.5 mg (intact uterus). Further investigations demonstrated a higher endogenous thrombin potential-based normalized activated protein C (APC) sensitivity ratio as one of the mechanisms for the elevated clotting propensity observed in CEE users This is in line with a recent large UK observational study of general female population aged 40–79 which found that among oral HRT, CEE(+MPA) had the greatest risk while E2(+dydrogesterone) had the lowest risk [16]. E2 has beneficial effects on several cardiovascular and uterine parameters, which could have far-reaching impact on long-term cardiovascular health and possibly fertility treatment outcomes,
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