Effects of a sequential combination of estradiol valerate and cyproterone acetate on the functional properties of the arterial wall in menopausal women

Several studies have shown that estrogen replacement therapy protects postmenopausal women against coronary artery disease. This protective effect has been ascribed to the hormone's effect on serum lipids, as well as a direct action on the vascular wall. Concurrent administration of a progestin to protect women from the risk of endometrial hyperplasia may alter the protective effects of estrogen. The aim of this study was to assess the evolution of the endothelial function in postmenopausal women given a sequential combination of oral 2 mg estradiol valerate for 11 days, followed by 2 mg estradiol valerate associated with 1 mg cyproterone acetate for ten days (Climène). Each 21-day sequence was followed by a seven-day treatment-free interval. The women received a three-month treatment course. Thirty-one healthy postmenopausal women participated in the study (median age: 51 years; range: 45-59 years). Flow-mediated dilatation (FMD), a reflection of endothelium-dependent vasomotor function, increased from 8.47% at baseline (range: 4.57-11.02%) to 9.64% (range: 7.07-13.12%) at the end of the first treatment cycle; i.e., a 15% increase over baseline (P < 0.0001). FMD further increased after three treatment cycles to 10.59% (range: 8.09-15.22%); i.e., a 28.6% increase over baseline (P < 0.0001). FMD at the end of the first combined sequence or after the 11 days of estradiol only were similar (delta = 0.25%; range: -2.31-5.81%; not significant). In conclusion, in postmenopausal women, a three-month sequential treatment combining estradiol valerate and estradiol valerate plus cyproterone acetate (Climène) has beneficial effects on endothelial function as demonstrated by the evolution of the FMD. There was no decrease in the effect of estradiol on FMD when cyproterone acetate was added to estradiol.