Vascular effects of progestogens

Alfred Mueck (DE)

[Mueck] Dept. of Women's Health, Tübingen

Large evidence from clinical and experimental studies supports a cardioprotective effect of estrogens in women. Estrogenic vascular effects depend on the stage of vascular function, i.e. the progress of atherosclerotic damage. Generally, progestogens may reduce or abolish beneficial estrogenic effects by, for instance, vasoconstrictory actions. The magnitude of any possible impact may depend on the ability of the vessel to compensate by counter-regulation. Negative progestogenic effects in atherosclerotic vessels, especially during long-term treatment, cannot be excluded but may be reduced by certain progestogens such as progesterone or dydrogesterone (retro-isomer of progesterone). Studies investigating biochemical markers acting as surrogates for direct vascular function have demonstrated that these progestogens mainly have have neutral effect or may even increase certain beneficial estrogenic effects like vasodilatation. The effects, however, are also related to pharmacokinetic parameters, so using higher dosages even those more "neutral" progestogens can antagonize the estrogenic action. On the other hand progestogens, well known to inhibit positive estrogenic action like MPA may act neutral in lower dosages. Likewise using NETA in combi-patches have shown to be neutral in contrast to oral application of NETA. Numerous studies are available on lipid and carbohydrate metabolism which have also consequences on vascular effects by acting within the complex mechanisms of atherosclerosis changing also vascular function. In addition data are available on clinical parameters such as on blood pressure and blood flow measurements. However, for investigating the effects in at-risk patients (i.e. women with pre-existing cardiovascular diseases) further research is needed.