Increased plasma concentrations of TGF-beta(1) after hormone replacement therapy

Objectives and design. Hormone replacement therapy (HRT) in postmenopausal women may reduce the cardiovascular risk. A dominant protective role of tra nsforming growth factor beta (TGF-beta(1)) on coronary arteries has been pr oposed. Lp(a) lipoprotein may block the activation of latent TGF-beta(1). G iven this background, we examined the effects of HRT on TGF-beta(1) and Lp( a) lipoprotein in 99 postmenopausal women. The women had angiographically d ocumented coronary heart disease (CHD) and were randomized to either sequen tial transdermal 17 beta-oestradiol for 14 weeks and then medroxyprogestero ne (MPA) for 14 days (HRT) or to a control group (C). Results. Serum levels of TGF-beta(1) were increased in the HRT group compar ed with the C group after 3 months' treatment and this effect was sustained after 12 months. There was a significant reduction in Lp(a) lipoprotein se rum levels after 3 months' treatment in the HRT group compared with the C g roup. However, after 12 months, no significant difference in changes in Lp( a) lipoprotein serum levels was detected between the two groups. Conclusion. The novel observation that transdermal 17 beta-oestradiol in po stmenopausal women increases levels of TGF-beta(1) and lowers the concentra tion of Lp(a) lipoprotein suggests yet another possible mechanism for the c ardioprotective effect of HRT. Whereas combination therapy of oestradiol an d MPA preserves the beneficial effect on TGF-beta(1), it reduces the unoppo sed oestradiol effects on Lp(a) lipoprotein.