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Oral 17ß-Estradiol Continuously Combined with Dydrogesterone Lowers Serum Lipoprotein(a) Concentrations in Healthy Postmenopausal Women¹

Departments of Obstetrics and Gynecology (V.M., P.K., E.R.A.P.-M., G.A.V., P.H.M.v.d.W., M.J.v.d.M.), Endocrinology (J.C.N.), and Clinical Chemistry (G.J.v.K.), Project Ageing Women and the Institute for Cardiovascular Research-Vrije Universiteit, University Hospital, Vrije Universiteit, Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Prof. Dr. P. Kenemans, University Hospital, Vrije Universiteit, Department of Obstetrics and Gynecology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. Serum Lp(a) concentrations increase after menopause, and postmenopausal estrogen replacement appears to decrease Lp(a) levels. In a randomized, double blind study, we examined the effects of 6-month treatment with daily 17ß-estradiol (E₂; 2 mg, orally) continuously combined with one of four dosages [2.5 mg (n = 41), 5 mg (n = 38), 10 mg (n = 38), and 15 mg (n = 20)] of dydrogesterone on fasting serum Lp(a) concentrations in 137 healthy postmenopausal women.

At baseline, no significant differences were noted among the four treatment groups. During the study period of 6 months the median serum Lp(a) concentration decreased significantly from 128 mg/L (range, 5–1660) to 110 mg/L (range, 1–1530) in the total population, corresponding to a reduction of 13% (P < 0.001). The percent changes in serum Lp(a) correlated positively with the percent changes in serum E₂ at 3 as well as 6 months of therapy (r = 0.38; P < 0.001 and r = 0.35; P < 0.001, respectively). A dose response of dydrogesterone on serum Lp(a) was not found. In addition, serum lipids and (apo)lipoproteins improved significantly in all four treatment groups.

In conclusion, oral E₂ continuously combined with dydrogesterone has beneficial effects on the lipid and lipoprotein profile and is effective in lowering Lp(a) concentrations in postmenopausal women.

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