Effect of hormone replacement therapy with the anti-mineralocorticoid progestin Drospirenone compared to tibolone on endothelial function and central haemodynamics in post-menopausal women Cristiana Vitale a, ⁎, Caterina Mammi a , Marco Gambacciani b , Novella Russo a , Ilaria Spoletini a , Massimo Fini a , Maurizio Volterrani a , Giuseppe M.C. Rosano a,c a Department of Medical Sciences, IRCCS San Raffaele, Roma, Italy b Department of Obstetrics and Gynecology, University of Pisa, Italy c Cardiovascular & Cell Sciences Institute, St Georges Hospital Medical School, London, UK abstract article info Article history: Received 22 August 2016 Accepted 6 November 2016 Available online xxxx Drospirenone (DRSP) is an antialdosterone agent with progestogenic and antiandrogenic effects. This compound, has been recently used in combination with 17β-estradiol (E2) as hormonal therapy in postmenopausal women and has been shown to exert a significant antihypertensive effect in hypertensive post-menopausal women. Aim of the present study was to compare the effect of DRSP/E2 with those of Tibolone (T) on endothelial function, ar- terial stiffness, and lipid profile of early postmenopausal women naïve on post-menopausal hormonal therapy. Twenty-four women met the inclusion criteria and entered the study. Women were randomized to receive either DRSP/E2 or T for 6 months. Blood pressure and heart rate were similar in both groups at baseline and at the end of the study. Compared to baseline, endothelial function assessed by Reactive Hyperemia (RH) significantly im- proved in women receiving E2/DRSP, whereas no significant differences between baseline and follow up were detected in women receiving Tibolone. Women receiving E2/DRSP showed a significant decrease in pulse wave velocity and Augmentation Index compared to baseline while no changes were observed in women receiv- ing Tibolone. The capacity of sera to trigger endothelial cells apoptosis in vitro measured by cell death assay was significantly reduced by E/DRSP but not by T (HFA-E 70 ± 5,6% vs HFD-E 41 ± 4,5%, p b 0,001). In conclusion, the present study shows that the association of Estradiol and Drospirenone as hormonal replacement therapy signif- icantly improves vascular parameters and the composition of sera relevant for vascular protection in early post- menopausal normotensive women. These effects are not shared by Tibolone. © 2016 Elsevier Ireland Ltd. All rights reserved. Keywords: Hormone replacement therapy Prognosis Endothelial function Drospirenone Pulse wave velocity Augmentation index 1. Introduction Post-menopausal estrogen deficiency is associated with an increased cardiovascular risk linked, among others, to the negative effect of ovar- ian hormones deprivation on cardiac functions and risk factors [1]. De- spite early studies have consistently reported the effectiveness of hormone replacement therapy (HRT) in reducing cardiovascular events in early postmenopausal women, the cardiovascular benefits of HRT have been questioned by the results of one single randomized con- trolled study conducted mainly in late post-menopausal women [2–4]. Although the reasons for these conflicting results are not readily appar- ent, and are possibly related to patient selection and the progestin used, new alternative HRT strategies for postmenopausal women are clearly warranted [1–18]. The increased cardiovascular risk in post-menopause is mainly relat- ed to the change in blood pressure and lipid profiles and in vascular re- activity coupled with a progressive impairment of glucose tolerance [1–19]. An important step in the development of post-menopausal hy- pertension and glicaemic disorders is the activation of the renin- angiotensin-aldosterone system (RAAS) that, in addition to its effect on target organ damage and progression of atherosclerosis, plays a key role in the impairment of vascular stiffness and endothelial function [1–22]. Although studies on the RAAS focused mainly on angiotensin II and its inhibition, experimental and clinical studies have shown that also aldosterone has an independent and relevant role in the pathogen- esis of cardiovascular and renal disease [23]. Drospirenone (DRSP) is a novel antialdosterone agent with proges- togenic and antiandrogenic effects. This compound, has been recently used in combination with 17β-estradiol (E2) as hormonal therapy in postmenopausal women and has been shown to exert a significant an- tihypertensive effect in hypertensive post-menopausal women [24]. However, whether DRSP/E2 could exert protective cardiovascular International Journal of Cardiology xxx (2016) xxx–xxx ⁎ Corresponding author at: Dipartimento di Scienze Internistiche Motorie e Sensoriali, Centro Ricerca Clinica e Sperimentale, IRCCS San Raffaele, Via della Pisana 235, Roma, Italy. E-mail address: cristiana.vitale@sanraffaele.it (C. Vitale). IJCA-24011; No of Pages 5 http://dx.doi.org/10.1016/j.ijcard.2016.11.149 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: C. Vitale, et al., Effect of hormone replacement therapy with the anti-mineralocorticoid progestin Drospirenone com- pared to tibolone on endothelial function and central..., Int J Cardiol (2016), http://dx.doi.org/10.1016/j.ijcard.2016.11.149