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Oral vs. Transdermal HRT to Reduce Lipoprotein(a) Levels

Am Fam Physician. 1999 Feb 15;59(4):988-991.

Lipoprotein(a) [Lp(a)] contains structural elements similar to low-density lipoprotein (LDL) and plasminogen that may impart both atherosclerotic and thrombogenic activity. Epidemiologic investigations have reported that Lp(a) plasma levels are higher in post-menopausal women than in premenopausal women. Treatment of postmenopausal women with hormonal therapy has been shown to significantly lower Lp(a) levels, by up to 50 percent. Meschia and associates conducted a prospective randomized trial to compare the effects of oral and transdermal hormone replacement therapy on Lp(a) and other plasma lipid levels in healthy post-menopausal women.

A total of 120 postmenopausal women were randomized to one of two therapeutic regimens: 60 women received 17b-estradiol transdermal patches, in a dosage of 50 mg daily, plus medroxyprogesterone acetate (MPA), in a dosage of 10 mg daily for 12 days every three months; the other 60 women received oral conjugated equine estrogen in a dosage of 0.625 mg daily plus MPA, in a dosage of 10 mg daily for 12 days every three months. Forty-one women served as control subjects. Baseline clinical characteristics were similar in both groups.

The mean plasma Lp(a) level decreased significantly (22 percent) after three months in women receiving oral estrogen, but no further decrease was observed after six and 12 months of therapy. Women treated with transdermal estrogen also showed a significant decrease (12 percent) in Lp(a) levels after three months. No further reduction in Lp(a) levels was observed after six and 12 months of therapy. The Lp(a) levels in the control group remained unchanged during the study period.

Plasma concentrations of total cholesterol were decreased with both transdermal and oral estrogen after three months of treatment. No additional reduction was demonstrated at six and 12 months. The LDL-cholesterol levels were decreased significantly with both treatments after three months of therapy. Increases in high-density lipoprotein (HDL) cholesterol were seen throughout the study in the group receiving oral estrogen. However, HDL levels did not change during transdermal estradiol therapy.

Results of this study demonstrate that both oral and transdermal hormone replacement therapy reduces the serum concentration of Lp(a) in postmenopausal women. Oral conjugated estrogen decreased Lp(a) levels by 22 percent after three months of treatment, but no further reduction was seen during the following months, confirming that the lowering effect is achieved soon after initiation of therapy and that there is no additive effect over time. For this study, both estrogen regimens were combined with oral MDA, which, when administered at 10 mg daily for 12 days every three months, had negligible effects on the antiatherogenic effects of estrogen.

The authors conclude that both oral and transdermal hormonal therapy effectively lower Lp(a) in postmenopausal women. The findings suggest that the hepatic first-pass of estrogen does not influence to a greater extent the effect of hormone replacement therapy on Lp(a) plasma concentrations. Lengthening the treatment interval also does not appear to achieve better outcomes. The addition of a progestational agent was not associated with any negative or confusing effects on lipoprotein levels.

Meschia M, et al. Effects of oral and transdermal hormone replacement therapy on lipoprotein(a) and lipids: a randomized controlled trial. Menopause. Fall 1998;5:157–62.


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