Effect on biochemical vasoactive markers during postmenopausal hormone replacement therapy: estradiol versus estradiol/dienogest

Objectives: Aim was to compare the effects of estradiol-only?; therapy with combined estradiol:progestin treatment on the excretion of vasoactive medi ators surrogating on possible effects in the vascular system. The progestin used was dienogest, a new C19-progestin with antiandrogenic properties. Me thods: Prospective. randomized trial, 25 healthy postmenopausal women treat ed for 3 months with estradiol valerate (2 mg/day) and 27 women with estrad iol valerate (2 mg/day) continuously combined with dienogest (2 mg/day). As sessment of the following markers or their stable metabolites in nocturnal urine: cGMP. serotonin. prostacyclin acid thromboxane. and urodilatin. Resu lts: Estradiol alone increased the excretion of cGMP and serotonin signific antly suggesting vasodilating effects. The prostacyclin/thromboxane ratio k nown to be crucial for the relation of vasorelaxation to vasoconstriction s ignificantly increased. No significant changes were found for urodilatin, w hich is known to elicit different effects in the cardiovascular and renal s ystem. respectively. Combined estradiol:dienogest therapy also led to signi ficant increases in cGMP and serotonin excretion suggesting that progestin addition for three months does not affect these markers. However, in contra st to estrogen-only treatment, there was no significant increase For the pr ostacyclin/thromboxane ratio, which can be explained by antagonistic action of the progestin. The excretion of urodilatin was increased significantly, which might be due to counterbalancing progestin effects in the renal vasc ular system. Conclusions: The changes in vasoactive markers suggest an estr ogen effect that is vasorelaxant. Since there were no significant differenc es between the two groups, possible vascular effects of the progestin dieno gest. fur the first time evaluated. might not be of clinical relevance, at least not in women without cardiovascular diseases. (C) 2001 Elsevier Scien ce Ireland Ltd. All rights reserved.