Effect of an oral contraceptive containing drospirenone on the renin-angiotensin-aldosterone system in healthy female volunteers.
Drospirenone is a new synthetic progestogen with both progestational, antimineralocorticoid and antiandrogenic properties. In combination with ethinylestradiol, it is being developed as an oral contraceptive which will contain 30 micrograms ethinylestradiol and 3 mg drospirenone (Yasmin, Schering AG, Germany). The effects of drospirenone alone, and in combination with ethinylestradiol, upon the renin-angiotensin-aldosterone system (RAAS) have been evaluated in healthy female volunteers. RAAS activity was assessed by measurement of plasma renin substrate (PRS) concentration (otherwise known as angiotensinogen), plasma renin activity (PRA), and plasma aldosterone (P-Aldo) concentration. An antimineralocorticoid effect was observed when volunteers received drospirenone alone at doses in the range 0.5-3.0 mg/day for one cycle. The effect was dose-dependent for P-Aldo but was not dose-dependent for PRA. When ethinylestradiol (30 micrograms) was combined with either 2 mg or 3 mg drospirenone and given to volunteers for three cycles, an increase in PRS was observed with both preparations, which was indicative of estrogenic stimulation, and increases in PRA and P-Aldo were shown which were indicative of an antimineralocorticoid effect of drospirenone. Increases in PRA and P-Aldo were significantly higher with the preparation containing 3 mg drospirenone in cycle 1 but not in cycle 3. The effect of the preparation containing 30 micrograms ethinylestradiol/3 mg drospirenone upon RAS activity was also compared with that of a commercially available preparation also containing 30 micrograms ethinylestradiol but combined with 150 micrograms desogestrel (Marvelon). Over a period of 13 cycles, increases in PRS were seen with both treatments, the effect being slightly more pronounced with 30 micrograms ethinylestradiol/150 micrograms desogestrel. A markedly greater increase in PRA was seen following treatment with 30 micrograms ethinylestradiol/3 mg drospirenone, and, in cycle 3, this difference was statistically significant. In contrast, P-Aldo was increased markedly with 30 micrograms ethinylestradiol/3 mg drospirenone in all measured cycles, whereas, in the 30 micrograms ethinylestradiol/150 micrograms desogestrel group, changes were minimal. The increases in PRA and P-Aldo are interpreted as endogenous counter-regulation against the antimineralocorticoid activity of drospirenone. PRS increases under all combinations are an expression of estrogenic stimulation. Measurement of body weight and blood pressure in the studies with combined ethinylestradiol and drospirenone revealed that drospirenone was associated with either stable body weight or with a slight loss in body weight, while blood pressure remained largely unchanged. Overall, the results indicate that 30 micrograms ethinylestradiol/3 mg drospirenone has a distinct antimineralocorticoid effect.
Department of Internal Medicine, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany.
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W
Oelkers
F M
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Helmerhorst
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W
Wuttke
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R
Heithecker
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D000736:Androstenes / Q000008:administration & dosage / Q000494:pharmacology*; D000808:Angiotensinogen / Q000097:blood; D003276:Contraceptives, Oral / Q000494:pharmacology*; D017135:Desogestrel / Q000008:administration & dosage / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000736:Androstenes; D003276:Contraceptives, Oral; D000451:Mineralocorticoid Receptor Antagonists; D000808:Angiotensinogen; D004997:Ethinyl Estradiol; D000450:Aldosterone; D017135:Desogestrel; D012083:Renin; C035144:drospirenone