WASHINGTON — The combination of drospirenone (a progestin with antialdosterone effects) and 17-β-estradiol as hormone therapy for hypertensive postmenopausal women not only reduces their hot flashes, but lowers their blood pressure as well, according to a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.
Treatment with the combination of drospirenone and 17-β-estradiol for an 8-week period produced significant reductions in systolic and diastolic 24-hour ambulatory and clinic blood pressure at 2- and 3-mg doses of drospirenone, reported Dr. William B. White, professor of medicine at the University of Connecticut, Farmington.
Drospirenone plus estradiol has been used for the treatment of menopausal symptoms and is Food and Drug Administration-approved for this indication at a dose of 0.5 mg drospirenone/1 mg estradiol (marketed in the United States as Angeliq by Berlex Laboratories Inc.). During its development, it was noted that at a higher drospirenone dose, the combination also had antihypertensive properties. It is currently being used in Europe, Asia, and the rest of the world at a dose of 2 mg drospirenone/1 mg estradiol, Dr. White told this news organization.
In a multicenter (42 U.S. centers and 22 European centers) trial, Dr. White and his colleagues evaluated the blood pressure-lowering efficacy of various doses of drospirenone (1, 2, or 3 mg) combined with 1 mg of estradiol in 750 postmenopausal women aged 45–75 years, with an untreated systolic blood pressure of 140–179 mm Hg and untreated diastolic blood pressure of 90–109 mm Hg. They also evaluated estradiol alone to elicit data on the effects of estrogen on ambulatory blood pressure, about which little is known, wrote Dr. White.
In addition, because drugs which induce aldosterone blockade have been shown to increase serum potassium, the researchers evaluated the metabolic effects of the combination therapy.
Following a single-blind, placebo phase for 3–4 weeks to establish baseline blood pressure and laboratory values, the women were randomized to one of the three combination treatment arms, to estradiol alone, or to placebo. Twenty-four-hour ambulatory blood pressure monitoring was done at baseline and at 8 weeks.
Drospirenone at the 2-mg dose reduced clinical systolic and diastolic blood pressures by a mean of 12.1 and 9.2 mm Hg, respectively; and by a mean of 13.8 and 8.5 mm Hg, respectively at the 3-mg dose. Drospirenone at the 1-mg dose was less effective, reducing systolic BP by a mean of 9.8 mm Hg and diastolic BP by a mean of 7.0 mm Hg. The blood pressure-lowering effect of estradiol (−7.6 mm Hg systolic and −5.9 mm Hg diastolic) was similar to that seen with placebo, Dr. White wrote.
Reductions in ambulatory blood pressure showed findings similar to clinic readings, although the combination with 1 mg of drospirenone also had marginal benefits compared with placebo and estradiol alone, he added.
Changes in potassium levels were similar in all groups: Five patients in each of the drospirenone groups and five in the placebo group developed a serum potassium less than or equal to 5.5 mEq/L. The mean maximal change from baseline in drospirenone-treated patients was not significantly different among the five treatment groups and ranged between 0.29 mEq/L and 0.37 mEq/L.
Regarding the combination's effect on lipid levels, total and LDL cholesterol levels also were lowered significantly in women taking drospirenone and estradiol, with a 13.6-mg/dL drop in LDL cholesterol at the 3-mg dose, a 10.4-mg/dL drop at the 2-mg dose, and a 12.2 drop at the 1-mg dose. Triglyceride levels were not affected, Dr. White wrote.
Side effects varied according to drospirenone dose; those seen with a frequency greater than 2% included breast discomfort, vaginal bleeding or spotting, and upper respiratory infection, according to the researchers.
“This is a novel progestin which actually impacts upon aldosterone and therefore has a dose-related reduction in blood pressure—especially the systolic blood pressure—which is associated with cardiovascular risk. We actually studied a full spectrum of doses, along with estradiol alone and placebo, so the strength of the study is that we actually had these two control groups showing that, in fact, it was the drospirenone that was the important component that lowered the blood pressure. And it did that without any significant metabolic consequences,” Dr. White said in an interview. Dr. White disclosed that he serves as a consultant for Berlex Laboratories Inc., which markets Angeliq, as well as other pharmaceutical companies.