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This version published online on October 26, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-1402
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Submitted on July 2, 2009
Accepted on September 25, 2009

Increased Apolipoprotein AI Production Rate and Redistribution of High-Density Lipoprotein Size Induced by Estrogen plus Progestin as Oral Contraceptive

Laurence Duvillard*, Guillaume Dautin, Emmanuel Florentin, Aline Jeannin, Jean-Paul Pais de Barros, Laurent Lagrost, Jean-Michel Petit, Philippe Gambert, and Bruno Vergès

Institut National de la Santé et de la Recherche Médicale Unité 866-Université de Bourgogne (L.D., G.D., E.F., A.J., J.-P.P.d.B., L.L., J.-M.P., P.G., B.V.), Faculté de Médecine, Dijon F-21000, France; Institut Fédératif de Recherche 100 (E.F., P.G.), Faculté de Médecine, Dijon F-21000, France; and Department of Endocrinology and Metabolic Diseases (J.-M.P., B.V.), Centre Hospitalier Universitaire Dijon, Hôpital du Bocage, Dijon F-21000, France

* To whom correspondence should be addressed. E-mail: laurence.duvillard{at}chu-dijon.fr.

Context: The impact of estrogen plus progestin as an oral contraceptive on high density lipoprotein (HDL) apolipoprotein (apo) AI metabolism in humans is poorly understood.

Objectives: This study was designed to measure the in vivo effect of Moneva (30 μg ethinylestradiol, 75 μg gestodene) on HDL apoAI production rate and fractional catabolic rate.

Design: Using 13C-leucine, we performed two kinetic studies in the fed state in 10 normolipidemic young women, before and 3 months after beginning Moneva.

Results: On Moneva, serum triglycerides increased by 12% (P = 0.03) in the fed state, whereas low-density lipoprotein and HDL cholesterol remained unchanged. HDL apoAI pool size and production rate were increased by 9.2% (67.3 ± 7.1 vs. 61.6 ± 6.7 mg ·1 kg-1; P = 0.05) and 26.5% (14.3 ± 2.7 vs. 11.3 ± 2.2 mg ·1 kg-1 ·1 d-1; P = 0.02), respectively. HDL apoAI fractional catabolic rate was not significantly modified. Three-month treatment by Moneva induced a shift of HDL size distribution from HDL2 toward HDL3 (HDL3 = 51.5 ± 8.1 vs. 46.5 ± 9.2% of total HDL; P = 0.02) and an increase in the proportion of apoAI among HDL components (38.8 ± 4.3 vs. 34.4 ± 2.8%; P = 0.01).

Conclusion: Oral contraception by estrogen plus progestin induces changes in HDL apoAI metabolism characterized by an increase in production rate and pool size, with a higher proportion of HDL3 particles. Whether or not these changes are beneficial to prevent atherosclerosis has to be explored further.







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