Effects of a New Hormone Therapy, Drospirenone and 17-β-Estradiol, in Postmenopausal Women With Hypertension

Abstract

Abstract-Drospirenone (DRSP), a progestin with antialdosterone activity, has been developed for hormone therapy in combination with 17-␤-estradiol (E2) in postmenopausal women. We evaluated the antihypertensive efficacy and safety of various doses of DRSP and E2 and estradiol alone in postmenopausal women with hypertension using ambulatory and clinic blood pressure (BP) monitoring. This was a randomized, double-blind clinical trial of 3 doses of DRSP combined with estradiol, estradiol alone, and placebo in 750 postmenopausal women with stage 1 to 2 hypertension between 45 to 75 years. Ambulatory and clinic BPs, potassium, aldosterone, and lipid measurements and adverse events were evaluated in postmenopausal women with stages 1 to 2 hypertension during 8 weeks of double-blind therapy. DRSP and E2 induced dose-related reductions in the ambulatory and clinic systolic BP with physiological increases in serum aldosterone. Significant decreases in 24-hour systolic pressure were observed at doses of 2 and 3 mg of DRSP combined with estradiol but not by estradiol alone or 1 mg of DRSP with estradiol. There were no significant changes from baseline in potassium in any treatment group. Small, significant reductions in total and low-density lipoprotein cholesterol occurred on all of the active treatments, and serum triglycerides did not change. Adverse event rates were low and similar across treatment groups. In conclusion, these data show that DRSP combined with E2 significantly reduces BP in postmenopausal women with hypertension and did not induce significant increases in serum potassium. These characteristics may lead to a new benefit for this novel hormone therapy in postmenopausal women with hypertension. Recently, experimental and clinical studies have implicated aldosterone, independent of angiotensin II, in the pathogenesis of significant cardiovascular and renal disease and demonstrated the benefit of aldosterone blockade in reducing a variety of cardiovascular and renal events. 6 -13 Drospirenone (DRSP) is a novel progestin with antialdosterone effects that, in combination with 17-␤-estradiol (E2), has been developed for use in postmenopausal women as a hormone therapy. 14 -16 The combination DRSP/E2 is approved for estrogen deficiency symptoms in postmenopausal women. During its development for relief of menopausal symptoms, DRSP/E2 was shown to have significant antihypertensive effects in studies of postmenopausal, hypertensive women alone or in combination with enalapril. [17][18][19] Furthermore, DRSP/E2 was found to have a significant antihypertensive effect in patients with and without type 2 diabetes mellitus and concomitant use of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. 20 When compared with other hormone therapies and oral contraceptives, DRSP results in a significantly greater increase in plasma aldosterone 14 -16 in response to the antialdosterone effect of the compound.The primary objective of this study was to determine whether this new hormone therapy has ...

Contracepção hormonal e sistema cardiovascular

“…Even so, it is still not possible to determine the beneficial effects of this contraceptive formulation on the blood pressure of users with high blood pressure 66 . This conclusion differs from that reached for HT in postmenopausal women, in which the compound (drospirenone and estradiol) was associated with decreased blood pressure in women that suffer from high blood pressure 67 . This does not apply to the association of drospirenone with EE in contraception.…”

Hypertension in women

“…2 Similar to oral contraceptives, HRT containing drospirenone seems to reduce BP due to its antimineralocorticoid receptor effects. The combination of 17-b-estradiol and drospirenone was tested in 27 Overall, HRT induces, if any, small changes in BP and should not preclude HRT use in either normotensive or hypertensive women. Nevertheless, all hypertensive women treated with HRT should have their BP measured initially and then at 3-6-month intervals depending on the difficulty of control.…”

Menopause, Estrogens, and Endothelial Dysfunction: Current Concepts

“…For instance, progestin molecules with androgenic properties may antagonize estrogen-dependent beneficial effects on lipids, 83 and a new molecule with antimineralocorticoid activity may reduce blood pressure in postmenopausal women with hypertension. 84 Progestins added to estrogen therapy seem to increase inflammatory markers. 72 In addition, medroxyprogesterone acetate associated with conjugated equine estrogens produces no effects 85 or inhibits endothelium-dependent vasodilatation stimulated by estrogens.…”