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Novel Progestin Plus Estradiol Improves Cardiovascular Markers

October 7, 2005

Novel progestin drospirenone, when administered in combination with estradiol, may spare or even improve cardiovascular markers, including low-density lipoprotein (LDL) levels, blood pressure levels and body weight.

The combined drospirenone-estradiol drug is manufactured by Berlex and marketed under brand name Angeliq.

Results of the double-blind, multi-center study were presented at the annual meeting of the North American Menopause Society and reported by MedPage Today on 3 October. The trial involved 142 post-menopausal women who received either estradiol alone or estradiol in combination with a variety of doses of drospirenone.

Drospirenone is a newly developed progestin derived from 17-alpha-spirolactone; it has progestogenic, anti-androgenic and anti-mineralocorticoid activity.

Study Results

Overall, researchers reported that, in women taking estradiol and drospirenone, total cholesterol and low-density lipoprotein were moderately reduced, and other markers showed some improvement. However, high-density lipoprotein (HDL) levels declined.

The women's weight either did not change or decreased, and the drugs showed no effect on blood pressure (although previous studies of this drug combination have shown improved blood pressure levels).

Previously, Angeliq has demonstrated anti-aldosterone and anti-androgenic properties. In this study, investigators studied the effects of estradiol plus one of four doses of drospirenone (0.5 mg, 1 mg, 2 mg or 3 mg) on blood pressure, serum lipids, and body weight. They then compared the results with results of women taking 1.0 mg of estradiol alone:

  • Body Weight: Women taking estradiol alone (2.1 mg) had an average weight change of a gain of 0.4 kg, whereas women taking estradiol plus the lowest dose of drospirenone had an average weight loss of 0.5 kg.
  • Cholesterol: Women taking only estradiol had a rise in total cholesterol rose of 1.3 mg/dL, whereas women taking both drugs versus had an average decrease of 16.0 mg/dL.
  • HDL: Among women taking only estradiol, HDL levels rose 7.6 mg/dL on average, compared with an average increase of 3.7 mg for women taking both drugs.
  • LDL: Women on estradiol alone showed an average decrease in LDL levels of 5.3 mg/dL, and an average increase in triglycerides of 9.7 mg/dL. For the women on both drugs, LDL decreased an average of 14.8 mg/dL and triglycerides decreased an average of 9.7 mg/dL.

In women taking estradiol plus the higher doses of drospirenone (1 mg, 2 mg and 3 mg, respectively), body weight was either unchanged (1-mg group), decreased an average of 1.2 kg (2-mg group) or increased an average of 1 kg (3-mg group). In these groups, the average reduction in total cholesterol ranged from 13.2 mg/dL to 18.5 mg/dL, while average reductions in LDL ranged from 12.5 mg/dL to 15.9 mg/dL.

Previous studies in hypertensive women treated with estradiol plus drospirenone have resulted in blood pressure reductions averaging approximately 8.6/5.8 mm Hg. However, in all groups in this study, blood pressure effects were neutral in all treatment groups, reported investigator David Archer, MD, of Eastern Virginia Medical School and director of the Contraceptive Research and Development Program at the Jones Institute for Reproductive Medicine.

"This is a highly effective combination for menopausal symptoms, with evidence of safety with minimal impact on weight and blood pressure," said Archer.

Berlex received FDA approval on 28 September for estradiol (2.1 mg) plus drospirenone at the daily dose of 0.5 mg (the lowest of four doses used in this study). Dr. Archer said he has no financial involvement with Berlex, according to MedPage Today.

NAMS: HRT With a Novel Progestin Sidesteps Some Unwanted Heart Effects, MedPage Today, 3 October 2005.
North American Menopause Society, 16th annual meeting, 28 September-1 October 2005, Abstract #S-16.

Posted: October 2005