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 replacement therapy (HRT) on endothelial function, measured as intraplatelet cyclic guanosine monophosphate (cGMP, mediator of nitric oxide), cyclic adenosine 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 study for 9 months.

Setting: The study was performed at the Department of Endocrinology, University Hospital, Malmö, Sweden.

Subjects: Fifty-one postmenopausal women participated in part 1 and 46 in part 2. Inclusion criteria included a history of amenorrhoea for at least 6 months before the study and body mass index >/= 24 kg m-2.

Intervention: Randomization for either placebo (n = 24) or HRT (n = 27). HRT was given as 2 mg oestradiol valerate for the first 3 months with the addition 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 (0.35-0.94) to 0.61 (0.42-3. 40) and 0.65 (0.43-1.08) pmol (109 platelets)-1 after 3 and 12 months, respectively (P = 0.01), whereas plasma ET-1 decreased from 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, significant 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 function which may account for anti-atherogenic effects of HRT in postmenopausal women, especially in smokers. No effects of HRT were seen upon monocyte activation.