Effects of a new oral contraceptive containing an antimineralocorticoid progestogen, drospirenone, on the renin-aldosterone system, body weight, blood pressure, glucose tolerance, and lipid metabolism

J Clin Endocrinol Metab. 1995 Jun;80(6):1816-21. doi: 10.1210/jcem.80.6.7775629.

Abstract

Combined hormonal oral contraceptives (OCs) may lead to a mild rise in blood pressure and body weight. In rare instances, large increments in blood pressure are measured. We investigated the effect of a combination of ethinyl estradiol (EE) plus a progestogen with antimineralocorticoid, i.e. natriuretic, properties [Drospirenone (DRSP)] on body weight, blood pressure, the renin-aldosterone system, atrial natriuretic factor, plasma lipids, and glucose tolerance. It is anticipated that this will lead to the development of an OC that does not raise body weight or blood pressure. Four groups of 20 women each received 30 micrograms EE plus 3 mg DRSP (group A), 20 micrograms EE plus 3 mg DRSP (group B), 15 micrograms EE plus 3 mg DRSP (group C), and, as a control OC, 30 micrograms EE plus 150 micrograms levonorgestrel (Microgynon, Schering; group D) for 6 months. During the OC-free control cycles before and after treatment and throughout treatment, the target parameters were measured. Between the pretreatment cycle and the sixth treatment cycle, mean body weight fell by 0.8 to 1.7 kg in groups A, B, and C (P < 0.05 vs. D), whereas it rose by 0.7 kg in group D. Systolic and diastolic blood pressures fell by 1-4 mm Hg in groups A, B, and C (significant for A and C vs. D) and increased by 1-2 mm Hg in group D. Renin substrate rose equally in all groups (P < 0.05), whereas PRA and plasma aldosterone rose significantly only in the DRSP groups, presumably due to sodium loss. In the DRSP groups, high density lipoprotein cholesterol rose (P < 0.05), in contrast to group D. Low density lipoprotein cholesterol fell slightly (P > 0.05), whereas triglyceride levels showed a stronger increase in the DRSP groups (P < 0.05) than in group D. All groups attained good cycle control; group A had the best. Side-effects were minimal. To our knowledge, this is the first report on a combined OC that leads to a small decrease in body weight and blood pressure. It may be especially beneficial for women susceptible for a gain in weight and a rise in blood pressure.

PIP: The potential of a new oral contraceptive (OC) containing drospirenone (DRSP) to avert the moderate increases in body weight and blood pressure often associated with use of existing combined OCs was investigated in a study of four groups of 20 German women each. Group A received 30 mcg of ethinyl estradiol (EE) and 3 mg of DRSP, Group B was administered 20 mcg of EE and 3 mg of DRSP, Group C received 15 mcg of EE and 3 mg of DRSP, and Group D was given a standard OC containing 30 mcg of EE and 150 mcg of levonorgestrel. Between the pretreatment cycle and the last (sixth) treatment cycle, mean body weight fell by 0.8-1.7 kg in Groups A, B, and C, but rose by 0.7 kg in Group D. Systolic and diastolic blood pressures fell by 1-4 mm Hg in Groups A, B, and C and rose by 1-2 mm Hg in Group D. Renin substrate rose equally in all four groups, while plasma renin activity, plasma aldosterone, and high density lipoprotein cholesterol rose significantly only in the three DRSP groups and serum triglyceride levels were significantly higher in Group D than in the three DRSP groups. Glucose tolerance increases were similar in all four groups. Finally, all groups--but especially Group A--experienced good cycle control and there were no serious side effects. These findings suggest that a combined OC containing DRSP may be especially beneficial for women who have a tendency to gain weight or experience a rise in blood pressure while taking OCs.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aldosterone / blood
  • Androstenes / administration & dosage
  • Androstenes / adverse effects
  • Androstenes / pharmacology*
  • Angiotensin I / blood
  • Blood Pressure / drug effects*
  • Body Weight / drug effects
  • Contraceptives, Oral, Combined / adverse effects
  • Contraceptives, Oral, Combined / pharmacology*
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / adverse effects
  • Ethinyl Estradiol / pharmacology
  • Female
  • Glucose Tolerance Test
  • Humans
  • Lipids / blood*
  • Mineralocorticoids / antagonists & inhibitors*
  • Renin / blood
  • Renin-Angiotensin System / drug effects*

Substances

  • Androstenes
  • Contraceptives, Oral, Combined
  • Lipids
  • Mineralocorticoids
  • Ethinyl Estradiol
  • Aldosterone
  • Angiotensin I
  • Renin
  • drospirenone