Hormone Replacement Therapy Lowers Plasma Lp(a) Concentrations

To study the responses of serum lipoproteins, apoproteins (apo's), and lipoprotein(a) (Lpa) to two frequently used hormone replacement therapies (HRTs), 120 postmenopausal women were randomly allocated to receive either transdermal therapy consisting of 28-day cycles with patches that delivered 17 beta-estradiol (50 micrograms/d) combined with cyclic oral medroxyprogesterone acetate (10 mg/d for 12 days per cycle) or continuous oral 17 beta-estradiol (2 mg/d) together with norethisterone acetate (1 mg/d) for 12 months. Blood samples were taken before and at 6 and 12 months of HRT. Concentrations of serum total, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol decreased by 14% (P < .001), 17% (P < .001), and 9% (P < .001) in the oral HRT group. Respective changes were 5.7% (P < .001), 4.8% (P < .05), and 4.7% (NS) in the transdermal group. Serum triglycerides remained unchanged in the oral group but decreased by 15.7% (P < .001) in the transdermal group. We observed only trivial changes in serum apo B levels. The changes in apo A-I levels paralleled those of HDL cholesterol in the oral HRT group. The concentration of serum Lp(a) decreased by 31% (P < .001) and 16% (P < .001) in the two groups. The combination of progestin and transdermal estrogen was not associated with any further change of Lp(a). The decrement in Lp(a) during therapy was positively associated with baseline Lp(a) levels in both groups (r = .96, P < .001 and r = .88, P < .001). Thus, both HRT regimens were highly effective in lowering elevated Lp(a) levels in postmenopausal women. The divergent responses of LDL and HDL cholesterol in the two HRT groups may influence the potential cardioprotective effects of the two HRT regimens. Prospective trials are needed to define the long-term effects with respect to coronary heart disease risk.