Changes in apolipoprotein B100-containing lipoprotein metabolism due to an estrogen plus progestin oral contraceptive: a stable isotope kinetic study.
BACKGROUND
Oral contraceptives with estrogen plus progestin are likely to influence apolipoprotein B (apoB)-containing lipoprotein metabolism by changing the expression of different enzymes or receptors that play a major role in this metabolism. However, the precise changes in apoB kinetic parameters induced by oral contraceptives that are now currently used are unknown.


OBJECTIVE
We studied the impact of Moneva, containing 30 microg ethinylestradiol and 75 microg gestodene, on the apoB production rate and fractional catabolic rate of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL).


METHODS
Using a 16-h [(13)C]leucine infusion, we performed an apoB kinetic study in nine normolipidemic women before and 3 months after beginning Moneva.


RESULTS
On Moneva, serum triglycerides increased moderately (+12%, P = 0.04) in the fed state, whereas serum LDL remained unchanged. LDL particles were richer in triglycerides in women on Moneva (7.5 +/- 1.5 vs. 4.3 +/- 1.0% of total LDL mass, P < 0.01). The apoB production rate of VLDL, IDL, and LDL increased by 49 (P = 0.04), 55 (P = 0.05), and 51% (P = 0.01), respectively. The fractional catabolic rate of apoB in LDL increased by 36% (P = 0.04). Consequently, the serum LDL apoB pool size remained unchanged (26.49 +/- 6.98 vs. 23.96 +/- 5.37 mg/kg).


CONCLUSIONS
Oral contraception with ethinylestradiol plus gestodene induces an increase in the production rate of apoB-containing lipoproteins all along the VLDL-->IDL-->LDL cascade. The increased production rate of apoB in LDL is counterbalanced by a higher fractional catabolic rate of apoB in LDL, thus precluding an increase in the concentration of atherogenic LDL particles.
Duvillard
Laurence
L
Institut National de la Santé et de la Recherche Médicale Unité 866, Université de Bourgogne, Faculté de Médecine, Dijon F-21000, France. laurence.duvillard@chu-dijon.fr
Dautin
Guillaume
G
Florentin
Emmanuel
E
Petit
Jean-Michel
JM
Gambert
Philippe
P
Vergès
Bruno
B
D000293:Adolescent; D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D004997:Ethinyl Estradiol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D009652:Norpregnenes / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D053299:Apolipoprotein B-100; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003276:Contraceptives, Oral; D008077:Lipoproteins, LDL; D009652:Norpregnenes; D014280:Triglycerides; C033273:Gestodene; D004997:Ethinyl Estradiol; D002784:Cholesterol; D007930:Leucine