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

Abstract

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

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

“…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.…”

“…In post-menopausal women with untreated stage 1 hypertension (SBP 140-159 mmHg; DBP 90-99 mmHg), treatment with E2 1 mg/DRSP 3 mg decreased both clinic and 24 h ambulatory blood pressure compared with placebo after 12 weeks of therapy [56]. The mean clinic blood pressure was decreased by 14.1/7.9 mmHg (SBP/DBP) from baseline in patients receiving E2/DRSP compared with only 7.1/4.3 mmHg in the placebo group (P< 0.0001).…”

“…Concomitant with the increase in sodium excretion via the RAAS, aldosterone receptor antagonists may also increase serum potassium concentrations, particularly in susceptible individuals [19,37]. However, E2/DRSP has not been associated with hyperkalemia (potassium ≥ 5.5 meq/L), even in high-risk patients [43,55,56]. When compared with placebo, treatment with E2 1 mg/DRSP 3 mg did not increase serum potassium concentrations or the incidence of hyperkalaemia, irrespective of concomitant use of ACE inhibitors, angiotensin II receptors antagonists or nonsteroidal anti-inflammatory drugs, and co-morbid diabetes mellitus [55].…”

PROGRESS IN PRIMARY ALDOSTERONISM: Mineralocorticoid antagonist treatment for aldosterone-producing adenoma

“…Eplerenone is given at doses of 25-50 mg/day to patients with cardiac failure (11,12), and at doses of 50-100 mg once or twice daily to patients with essential hypertension (13,14). It has been tested in patients with PA at doses from 50 to 300 mg/day in one or two daily doses (see below for details) (15,16). In patients with essential hypertension, there were no differences in side effects between eplerenone and placebo (14).…”

The use of lowest doses of menopausal hormone therapy

“…Результаты многих исследований с хорошим ди-зайном показали, что другие режимы терапии, поми-мо тех, что применялись в Womens Health Initiative (WHI): конъюгированные эквинные эстрогены (КЭЭ)/медроксипрогестерона ацетат (МПА), вклю-чающие новейшие прогестины, более низкие дозы гормонов, а также парентеральные формы, могут быть столь же эффективными для лечения менопау-зальных симптомов и при этом более безопасными [12][13][14].…”