Effect of hormone replacement therapy on lipoprotein(a) and lipid levels in postmenopausal women. Influence of various progestogens and duration of therapy.

BACKGROUND

Estrogen replacement therapy in postmenopausal women reduces the risk of coronary artery disease. One of the possible mechanisms of this effect is the modification of lipid profiles. However, there is controversy concerning the effects on lipoprotein(a) [Lp (a)] and lipid levels of progestogens administered with estrogen.

METHODS

Five hundred fifty-one postmenopausal women were divided into 5 groups: group 1, 0.625 mg of conjugated equine estrogen (CEE) (n = 140); group 2, 0.625 mg of CEE plus 5 mg of medroxyprogesterone acetate (MPA) (n = 97); group 3, 0.625 mg of CEE plus 10 mg of MPA (n = 109); group 4, 2 mg of estradiol valerate plus 0.5 mg of norgestrel (n = 134); and group 5, control (n = 71). The Lp(a) and lipid levels were measured before and 2, 6, and 12 months after hormone replacement therapy.

RESULTS

Estrogen replacement therapy for 12 months lowered the Lp(a) level by 37.1%. The addition of progestogen attenuated the Lp(a)-lowering effect of estrogen. The high-density lipoprotein cholesterol (HDL-C) level was markedly increased in group 1 (16.5%), was moderately increased in groups 2 (10.8%) and 3 (11.3%), and was not changed in group 4. The low-density lipoprotein cholesterol level was decreased by 10.9% to 17.6% in all the treatment groups. Estrogen replacement therapy for 2, 6, and 12 months raised the HDL-C level by 7.2%, 17.4%, and 17.8%, respectively. In the group with combined estradiol plus norgestrel therapy, the HDL-C level was decreased after 2 months and was not changed after 6 and 12 months. The groups that received CEE plus MPA showed intermediate effects between the group that received CEE only and the group that received estradiol plus norgestrel.

CONCLUSIONS

Combined estrogen and progestogen therapy may have effects on the heart different from those of estrogen therapy alone because of adverse impact of progestogens on Lp(a) and HDL-C levels. The effects of progesterones were dependent on the androgenic potency of progestogen and the duration of therapy.