Changes in apolipoprotein B100-containing lipoprotein metabolism due to an estrogen plus progestin oral contraceptive: a stable isotope kinetic study

J Clin Endocrinol Metab. 2010 May;95(5):2140-6. doi: 10.1210/jc.2009-2480. Epub 2010 Mar 3.

Abstract

Context: 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.

Objectives: 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).

Design: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Apolipoprotein B-100 / blood
  • Apolipoprotein B-100 / metabolism*
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / drug effects
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects
  • Contraceptives, Oral / therapeutic use*
  • Ethinyl Estradiol / therapeutic use*
  • Female
  • Humans
  • Kinetics
  • Leucine / blood
  • Lipoproteins, LDL / blood*
  • Lipoproteins, LDL / drug effects
  • Norpregnenes / therapeutic use*
  • Triglycerides / blood
  • Young Adult

Substances

  • Apolipoprotein B-100
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Contraceptives, Oral
  • Lipoproteins, LDL
  • Norpregnenes
  • Triglycerides
  • Gestodene
  • Ethinyl Estradiol
  • Cholesterol
  • Leucine