Progestogens and target tissues: vascular systems

Progestogens were mostly used in hormone replacement therapy (HRT) in the postmenopause. Therefore, our knowledge about cardiovascular effects mainly originates from studies using HRT, whereby the progestogen effects were assessed according to clinical endpoints, metabolic effects and influence on vascular markers in vitro or in vivo, respectively. Furthermore, the progestogens can be characterised in terms of their partial receptor properties by specific experimental models. These properties can positively or negatively influence the vascular system. Concerning the direct vascular effects, currently research is focussing on biochemical vascular active markers. Although evidence strongly supports that some of these markers can be used as predictors of certain cardiovascular events, it remains to be established that modifying circulating levels of these markers will influence the outcomes. These experiments, however, strongly indicate that for the progestogens no class-effects can be postulated. In HRT progestogens are primarily used to get endometrial safety, which should be fulfilled by all progestogens. Since in terms of the vascular system it is difficult to predict the net-overall effect due to the different complex partial effects, we preferentially recommend progestogens derived from progesterone which are rather neutral in terms of the vascular system for risk patients but effective in the endometrium, i.e. maintaining atrophic endometrium during long-term continuous combined HRT. For women with hypertension especially HRT regimens can be recommended, which have been shown to stabilize or even lower blood pressure during well designed studies like with 24h-ambulatory blood pressure assessments. Further research is necessary to investigate the possibility of a more differential usage of the various progestogens regarding their effects on vascular systems.