Hormone replacement therapy in healthy postmenopausal women. Effects on intraplatelet cyclic guanosine monophosphate, plasma endothelin-1 and neopterin

Objectives. To evaluate beneficial effects of postmenopausal hormone replac ement therapy (HRT) on endothelial function, measured as intraplatelet cycl ic guanosine monophosphate (cGMP, mediator of nitric oxide), cyclic adenosi ne monophosphate (cAMP, mediator of prostacyclin) and plasma endothelin-1 ( ET-1), and on monocyte activation, measured as plasma neopterin. Design. Part 1: double-blind randomized trial for 3 months; part 2: open st udy for 9 months. Setting. The study was performed at the Department of Endocrinology, Univer sity Hospital, Malmo, Sweden. Subjects. Fifty-one postmenopausal women participated in part 1 and 46 in p art 2. Inclusion criteria included a history of amenorrhoea for at least 6 months before the study and body mass index greater than or equal to 24 kg m(-2). Intervention. Randomization for either placebo (n = 24) or HRT (n = 27). HR T was given as 2 mg oestradiol valerate for the first 3 months with the add ition of 10 mg medroxyprogesterone for 10 days every third month thereafter . Measurements. Performed at baseline and after 3 and 12 months of the study. Results. In the HRT group, intraplatelet cGMP increased from 0.56 (0.35-0.9 4) to 0.61 (0.42-3.40) and 0.65 (0.43-1.08) pmol (10(9) platelets)(-1) afte r 3 and 12 months, respectively (P = 0.01), whereas plasma ET-1 decreased f rom 3.2 (1.1-6.8) to 2.0 (0.8-5.1) and 1.8 (0.4-15.4) pg mL(-1) (P < 0.001) . Intraplatelet cAMP and plasma neopterin were unchanged. When smokers (n = 15) and non-smokers (n = 12) in the HRT group were analysed separately, si gnificant effects were seen only amongst smokers. The control group showed unchanged levels of cGMP, cAMP, ET-1 and neopterin. Conclusions. These data suggest beneficial effects of HRT on endothelial fu nction which may account for anti-atherogenic effects of HRT in postmenopau sal women, especially in smokers. No effects of HRT were seen upon monocyte activation.