Many reports have shown that hormone replacement therapy(HRT) in postmenopausal women decreases lipoprotein(a)[Lp(a)]. However these had small numbers of subjects, short duration of therapy, or comparisons of only a few regimens. The influences of progesterone on Lp(a) and lipids, administered with estrogen, are controversial.

Five hundred and fifty-one postmenopausal women were divided into 4 groups : group A ; 0.625mg conjugated equine estrogen(CEE)(m=140), group B ; 0.625mg CEE plus 5mg medroxyprogesterone acetate(MPA)(m=97), group C ; 0.625mg CEE plus 10mg MPA(n=109), and group D ; 2mg estradiol valerate(E2) plus 0.5mg norgestrel(N)(n=134) and group E ; control(n=71). Lp(a) and lipids levels were measured before and 12 months after HRT.

Estrogen replacement therapy(ERT) for 12 months lowered Lp(a) level by 37.1%. The addition of progesterone attenuated the Lp(a)-lowering effect of estrogen and decreased by 27.7%, 29.6%, and 30.3% in groups B(p<0.05), C(p<0.05), and D(p<0.0001) respectively. High density lipoprotein cholesterol(HDL-C) was increased markedly in group A(16.5%), increased moderately in groups B(10.8%) and C(11.3%), and not changed in group D. Low density lipoprotein cholesterol was decreased by 10.9%, 13.7%, 11.3%, and 17.6% in groups A, B, C, and D respectively.

Reduction of Lp(a) with estrogen replacement therapy may be one of mechanisms for cardioprotective effect in postmenopausal women. The combined therapy of estrogen and progesterone may reveal different effects on heart due to adverse actions of progesterone on Lp(a) and HDL-C. The variations in the androgenic potency of progesterone may explaine inconsistent results on HDL-C in previous studies.