The effects of estrogen and hormone replacement therapy on platelet activity: a review

Many studies have shown that an increase in cardiovascular disease in women is related to hormonal changes occurring particularly after menopause with increasing age. While the results of large clinical trials reporting no benefit of hormone replacement therapy (HRT) in cardiovascular disease have been known for some time, there is an increasing body of knowledge regarding the various mechanisms by which estrogen modulates platelet function that could in part explain the higher cardiovascular risk occurring in postmenopausal women and potential benefits of HRT on cardiovascular health. Our review summarizes our current knowledge regarding the effect of endogenous and exogenous estrogen on platelet activity, which can help researchers design future studies. We collected information from 21 peer-reviewed articles published from 1993 to 2021. Studies have indicated that postmenopausal women have higher platelet activity than premenopausal women, which can increase the risk of thrombo-embolic events and cardiovascular disease. Although some studies have reported pro-thrombotic effects of estrogen replacement therapy such as increased platelet activation and adhesion, other studies demonstrated decreased platelet aggregation by inhibiting GP IIb/IIIa receptor expression. This is mediated by estrogen receptors on the platelet membrane in a non-genomic manner and suggests an opportunity for the usage of estrogen replacement therapy with subtle changes in the formulation and route, particularly if started early after menopause. The effect of estrogen on platelet activity is promising as an important factor in reducing the risk of cardiovascular events, warranting further investigation.