Hormone therapy and cardiovascular risk markers and disease: focus on progestagens

Biological studies have demonstrated estrogen's beneficial effect on cardiovascular risk factors, including plasma lipoproteins, atherogenesis, vascular reactivity, inflammation and antioxidative activity. Additionally, observational studies have supported a cardioprotective effect of hormone therapy (HT), although an underlying healthy-user effect may account for these observations. Progestagens are added to protect against an increased risk of endometrial cancer observed with unopposed estrogen treatment. The inclusion of progestagen in HT has been associated with possible adverse cardiovascular outcomes. Recent, large-scale, randomized clinical studies did not confirm a beneficial cardiovascular effect of HT. On the contrary, an increased risk was found with continuous combined estrogen-progestagen regimens. The progestagen used in these trials was medroxyprogesterone acetate and other progestagen components have only been sparsely elucidated. The purpose of the present review is to outline some of the modifying effects of different progestagens on the actions of estrogen on cardiovascular risk markers and clinical end points observed in biological, observational and clinical studies.