Progesterone attenuates the beneficial effects of hormone replacement therapy on large artery elasticity in hypertensive postmenopausal women

Abstract

Nowadays, based mainly on the results of the Heart and Estrogen/progestin Replacement Study (HERS), the cardiovascular beneficial effects of hormonal replacement therapy (HRT) on cardiovascular morbidity and mortality, are in doubt. In the present study we sought to define the possible differential effects of combined and uncombined HRT on large artery elastic properties in hypertensive postmenopausal women. Towards this end, we studied aortic compliance in 56 postmenopausal women (aged 52 years, 3.4years after menopause) with untreated, mild essential hypertension. Our pooled population was randomized to conjugated estrogen alone (n=20), estrogen plus medroxyprogesterone (n=20) or placebo (n=16) and classified into three groups respectively. At baseline and after 12 weeks of treatment, we evaluated the aortic elasticity non-invasively on the basis of pulse wave velocity (PWV) measurements. In the entire study population BMI was 27.2 Kgr/m2, office BP146/93 mmHg, left ventricular mass index (LVMI) 104±26 gr/m2, and mean plasma levels of total cholesterol 230mg/d. At baseline the three groups were matched for age, time since menopause, smoking status, office blood pressure, BMI, LVMI and PWV values. At 12 weeks of treatment, in the women receiving estrogen alone, aortic PWV was significantly reduced (231 vs 209 cm/sec, p<0.005), while in the women receiving combined HRT or placebo, PWV did not change (232 vs 228 and 233 vs 230 cm/sec, respectively, p=NS for both cases). In all three groups, blood pressure and heart rate values did not change significantly after treatment. At baseline, aortic PWV had a positive correlation with the age of women (r=0.32, p<0.05) and LVMI (r=0.29, p<0.05). In conclusion, long-term combined HRT has no beneficial effects on the augmented large artery stiffness in hypertensive postmenopausal women. These findings confirms the view that progesterone may attenuate the beneficial effects of unopposed HRT on vascular function in the above-mentioned essential hypertensive patients.