Drospirenone in combination with estrogens: for contraception and hormone replacement therapy

Abstract

Progesterone has a high affinity for the mineralocorticoid receptor and is an antagonist of aldosterone. Almost all synthetic progestogens are devoid of an antimineralocorticoid effect, and are unable to antagonize the salt-retaining effect of estrogens. This property could be one cause of the weight gain and increase in blood pressure associated with the use of combined oral contraceptives and, in some susceptible women, with postmenopausal hormone replacement therapy (HRT). This review illustrates the results of clinical studies with drospirenone, a new progestogen with antialdosterone activity.In normally menstruating women, 3 mg drospirenone per day, taken from day 5 to day 25 of the cycle, inhibits ovulation. A combination of 3 mg drospirenone with 30 μg ethinylestradiol (Yasmin®, Schering AG, Berlin, Germany) is a highly effective and well-tolerated oral contraceptive, with an overall Pearl Index of 0.57 and an adjusted Pearl Index of 0.09. In addition, this combination leads to mild natriuresis and a slight compensatory activation of the renin–aldosterone system. This effect hasbeen clinically demonstrated: compared with an oral contraceptive containing 30 μg ethinylestradiol and 150 μg levonorgestrel, 30 μg ethinylestradiol/3 mg drospirenone, given over 6 months, led to slight decreases in body weight and blood pressure.For postmenopausal HRT, 2 mg drospirenone was combined with 1 mg 17β-estradiol (Angeliq®, Schering AG, Berlin, Germany) for continuous treatment. To evaluate the endometrial safety of this combination, data were assessed from 520 postmenopausal women receiving 1 mg 17β-estradiol and drospirenone (1, 2 or 3 mg per day) for at least 100 weeks. There were no cases of hyperplasia or carcinoma during the entire study period, and 85–92% of women had an atrophic/inactive endometrium.Data from two studies, with a treatment duration of at least 6 months, demonstrated adecrease in mean systolic blood pressure of 1.8 mmHg and a decrease in mean diastolic blood pressure of 3.8 mmHg, after treatment with 1 mg 17β-estradiol/2 mg drospirenonefor 28 weeks. However, in a subgroup of slightly hypertensive women (initial blood pressure of more than 140/90 mmHg), the mean decrease in systolic bloodpressure after 28 weeks of treatment with 1 mg 17β-estradiol/2 mg drospirenonewas 12.5 mmHg, and the mean decrease in diastolic blood pressure was 9.4 mmHg.Since high blood pressure is a cardiovascular risk factor, the use of drospirenone may exert a beneficial effect in this regard. More prolonged studies need to be performed, in order to demonstrate whether negative cardiovascular end-points can be reduced by the new progestogen.In conclusion, drospirenone is not only a safe option for women using oral contraceptives or HRT, but it may offer new medical benefits, via its antimineralocorticoid and antialdosterone effects and its potential to decrease water retention and blood pressure.