Additive effect of drospirenone/17-β-estradiol in hypertensive postmenopausal women receiving enalapril1

Preston, Richard A.; Alonso, Alberto B.; Panzitta, Darlene; Zhang, Paul; Karara, Adel H.

doi:10.1016/s0895-7061(02)02980-1

Cited by 52 publications

(38 citation statements)

References 29 publications

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“…However, one cannot rule out the possibility of a natural ageing effect, such as that observed in the Framingham Heart Study [51], given the absence of a control group or defined endpoints. A number of well-designed trials (see Table 2) have consistently demonstrated a significant blood pressure-lowering effect with DRSP plus E2 in postmenopausal women [43,[54][55][56]. This is consistent with the potent anti-aldosterone activity of DRSP.…”

Section: The Effect Of Drsp On Blood Pressuresupporting

confidence: 56%

“…E2/DRSP significantly reduced 24 h mean (±S.E.) SBP by 9 mmHg (±1.4) and DBP by 5 mmHg (± 1.2) from baseline (both P < 0.05), whereas no change in blood pressure was observed in the placebo plus enalapril group [54]. These findings show that E2/DRSP has added benefits on blood pressure when used in combination with other anti-hypertensive agents.…”

Section: The Effect Of Drsp On Blood Pressurementioning

confidence: 69%

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Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism

2006

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Unlike other currently available progestogens, drospirenone (DRSP) has a pharmacological profile, which closely mimics that of endogenous progesterone, most notably potent anti-aldosterone and anti-androgenic effects. Consequently, DRSP, when combined with 17β-estradiol (E2) as hormone replacement therapy (HRT), offsets E2-related water and sodium retention by blocking the mineralocorticoid receptor. This review evaluates the potential benefits offered by DRSP as the progestin component of HRT with respect to its anti-aldosterone activity, which translates into positive effects on body weight and blood pressure in clinical trials of continuous, combined E2/DRSP in post-menopausal women. In a 1 -year, large-scale, randomised, controlled trial, E2 1 mg/DRSP 2 mg significantly decreased mean body weight by 1.2 kg versus baseline (P < 0.001), whereas patients receiving E2 1 mg gained weight. E2 1 mg/DRSP 2 mg also significantly lowered mean systolic blood pressure (SBP) by 9.0 mmHg from baseline (P < 0.05) versus 3.7 mmHg in the E2 1 mg group (P = 0.220) in a sub-group of hypertensive women. In addition, E2/DRSP was not associated with hyperkalemia (potassium ≥ 5.5 meq/L) irrespective of concomitant use of ACE inhibitors, angiotensin II receptor antagonists or non-steroidal anti-inflammatory drugs, and co-morbid diabetes mellitus. In summary, as well as effectively treating climacteric symptoms, DRSP 2 mg combined with E2 1 mg has shown positive effects on body weight and blood pressure in clinical trials, most likely due to DRSP's anti-aldosterone properties. This combination may therefore offer an alternative therapeutic option with additional benefits beyond current HRT agents for symptomatic postmenopausal women.

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Section: The Effect Of Drsp On Blood Pressuresupporting

confidence: 56%

Section: The Effect Of Drsp On Blood Pressurementioning

confidence: 69%

Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism

2006

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“…The estimated sample SD of 11 mm Hg used in the calculation was obtained from the results of a previous study. 17 The sample size calculation was based on an assumed dropout rate of 10%.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…14 -16 DRSP/E2 has been shown to have significant antihypertensive effects in a shortterm study of postmenopausal, hypertensive women treated with enalapril. 17 When compared with other hormone therapies and oral contraceptives, DRSP yields a much greater rise in plasma aldosterone 14 -16 in response to the antimineralocorticoid effect of the compound.…”

mentioning

confidence: 99%

Antihypertensive Effects of Drospirenone With 17β-Estradiol, a Novel Hormone Treatment in Postmenopausal Women With Stage 1 Hypertension

et al. 2005

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Background-Drospirenone (DRSP) is a novel progestin with antimineralocorticoid activity that has been developed for hormone therapy in combination with 17␤-estradiol (E2) in postmenopausal women. In prior studies with DRSP in postmenopausal women that were focused on relief of menopausal symptoms, DRSP/E2 yielded significant reductions in blood pressure (BP). Methods and Results-The effects of 3 mg DRSP/1 mg E2 on clinic and 24-hour ambulatory BP as well as potassium homeostasis were evaluated in postmenopausal women with stage 1 hypertension (systolic, 140 to 159 and/or diastolic, 90 to 99 mm Hg) in a 12-week, multicenter, double-blind, randomized, placebo-controlled study. Clinic BPs were measured at baseline and at 2, 4, 6, 8, and 12 weeks of therapy, whereas potassium was measured at 2, 6, and 12 weeks of therapy. Ambulatory BP was performed in a substudy at baseline and at the end of the trial. In the intention-to-treat population of 213 women, the clinic BP was reduced significantly on DRSP/E2 (clinic BP, Ϫ14.1/Ϫ7.9 for DRSP/E2 versus Ϫ7.1/Ϫ4.3 mm Hg for placebo, PϽ0.0001). In the subgroup of 43 women with ambulatory BP monitoring, the 24-hour BP fell by Ϫ8.5/Ϫ4.2 mm Hg versus Ϫ1.8/Ϫ1.6 mm Hg on placebo (Pϭ0.002/0.07). There were no significant changes from baseline in potassium levels or in the incidence of hyperkalemia (Ն5.5 meq/L) on DRSP/E2 compared with placebo. Conclusions-Combination

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“…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.…”

mentioning

confidence: 97%

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

et al. 2006

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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 ...

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Additive effect of drospirenone/17-β-estradiol in hypertensive postmenopausal women receiving enalapril1

Cited by 52 publications

References 29 publications

Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism

Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism

Antihypertensive Effects of Drospirenone With 17β-Estradiol, a Novel Hormone Treatment in Postmenopausal Women With Stage 1 Hypertension

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

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