Hormone replacement therapy with estradiol valerate and cyproterone acetate: effects on endothelium-dependent vasodilatation and arterial wall compliance.
OBJECTIVE
to evaluate changes in vasomotor endothelium function and elastic properties of the brachial artery in postmenopausal women beginning hormone replacement therapy (HRT) with Climen(R), a 28-day sequential therapy combining estradiol valerate (E2V) 2 mg/day D1-D21 with cyproterone acetate (CPA) 1 mg/day D12-D22, followed by a 7-day treatment-free interval.


METHODS
Thirty-one women with natural or surgical menopause were included in an open multicenter study. Before treatment, at the end of the estrogen-only phase of cycle 1, and after the combined phase in cycles 1 and 3, endothelium-dependent vasodilatation (EDVD%) in the brachial artery was measured by the post-ischemia increase of the inner diameter, and pulse wave velocity (PWV) was measured in the same artery by simultaneous continuous wave Doppler and photo-plethysmography.


RESULTS
compared to pre-treatment values, the median increase in EDVD was 14.3% after cycle 1 (P=0.0001) and 27.9% after cycle 3 (P=0.0001). CPA did not alter the effect of E2V on EDVD in cycle 1. Median arterial systolic pressure was unchanged, but median diastolic pressure fell from 70 to 67.5 mmHg (P=0.04) after cycle 3. Median PWV was reduced by 0.76 m/s after cycle 3 (relative reduction -9.3%) (P=0.035). There was a significant correlation between PWV and EDVD changes from pre-treatment values at the end of the 3rd cycle.


CONCLUSIONS
treatment of postmenopausal women with E2V/CPA led to an immediate and significant improvement in endothelium-dependent vasodilatation. The estrogen-related vasomotor effect was not suppressed by the progestogen CPA. The WV changes are consistent with slower improvement of arterial compliance in some women. The non-invasive measurement of EDVD and PWV is a convenient method for the evaluation of both mechanical and functional effects of combination HRT on the arterial wall.
Mares
Pierre
P
Department of Gynecology and Obstetrics, University Hospital Center, Nîmes, France.
Dauzat
Michel
M
Abramovici
Yves
Y
D000284:Administration, Oral; D001916:Brachial Artery / Q000187:drug effects* / Q000502:physiology; D016022:Case-Control Studies; D017373:Cyproterone Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D005602:France; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011673:Pulsatile Flow; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D017373:Cyproterone Acetate; D004958:Estradiol