Impact of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol on cardiovascular markers in women diagnosed with premature ovarian insufficiency or an early menopause: a randomised pilot trial.

OBJECTIVE: To compare the difference between micronised progesterone (MP) and medroxyprogesterone acetate (MPA) in combination with transdermal oestradiol (t-E2) on cardiovascular disease (CVD) risk markers in women diagnosed with an early menopause and premature ovarian insufficiency (EMPOI). BACKGROUND: The European Society for Cardiology has identified carotid femoral pulse wave velocity (cfPWV) as the gold standard cardiogenic biomarker for risk stratification of arterial disease. Menopause has been shown to augment the age-dependent increase in arterial stiffness, with hormone replacement therapy (HRT) being the mainstay of management of women diagnosed with EMPOI. STUDY DESIGN: A pilot randomised prospective open-label trial. Women were randomised to either cyclical MP (Utrogestan® 200mg) or MPA (Provera® 10mg) in conjunction with t-E2 (Evorel® Patches 50mcg/day) for 12 months. Seventy-one subjects were screened, and baseline data are available for 57 subjects. MAIN OUTCOME MEASURE: Carotid-femoral pulse wave velocity (cfPWV). RESULTS: PWV did not significantly change from baseline in either treatment arm. MP + t-E2 demonstrated a positive effect on traditional CVD markers, with a significant improvement seen in cardiac output (CO) (0.71±1.01mL/min, 95% CI 0.20 to 1.21) and reduction in diastolic blood pressure (DBP) (-3.43±6.31mmHg, 95% Cl -6.57 to -0.29) and total peripheral resistance (TPR) (-0.15±0.19mmHg⋅min⋅mL-1, 95% CI -0.24 to -0.05) after 12 months. MPA + t-E2, in contrast, did not demonstrate significant changes from baseline in traditional haemodynamic parameters. CONCLUSION: The positive changes in traditional markers were not reflected in the cardiogenic biomarker, cfPWV, which has demonstrated a higher positive predictive value for cardiovascular events than traditional measurements.