Differential Effects of Estrogen and Progestin on Apolipoprotein B100 and B48 Kinetics in Postmenopausal Women

Abstract

The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B-containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo-controlled, randomized, double-blind crossover study. Each subject received placebo, conjugated equine estrogen (CEE, 0.625 mg/day) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) for 8 weeks in a randomized order, with a 4-week washout between phases. Main outcomes were the fractional catabolic rate (FCR) and production rate (PR) of apo B100 in triglyceride-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low -density lipoprotein (LDL) and of apo B48 in TRL. Compared to placebo, CEE increased TRL apo B100 PR (p = 0.04). CEE also increased LDL apo B100 FCR (p = 0.02), but this effect was offset by a significant increase in LDL apo B100 PR (p = 0.04). Adding MPA to CEE negated the CEE effects resulting in no significant changes in TRL apo B100 PR and LDL apo B100 FCR and PR relative to placebo. Relative to placebo, during CEE there was a trend toward a reduction in plasma apo B48 concentrations and PR (p = 0.07 and p = 0.12, respectively). Compared with CEE, CEE + MPA significantly increased TRL apo B48 FCR (p = 0.02) as well as apo B48 PR (p = 0.01), resulting in no significant changes in apo B48 concentration. Estrogen and progestin have independent and opposing effects on the metabolism of the atherogenic apo B100- and apo B48-containing lipoproteins.

The correlation of the fecal microbiome with the biochemical profile during menopause: a Brazilian cohort study

“…Our results suggest that the increase in LDL observed in premenopausal and postmenopause contributes to an increase of ApoB in these women, as previously described [ 28 ], and women who leave the reproductive phase and go through pre- and postmenopause tend to present increased levels of LDL and ApoB, as previously reported [ 29 ]. Observing these lipidic alterations in Brazilian women is important since higher levels of LDL and ApoB have been correlated with a higher risk of cardiovascular disease [ 30 , 31 ], which, along with the loss of endothelial protection promoted by estrogens, can harm women's health.…”

Sex-Specific Differences in Lipoprotein Production and Clearance

“…The addition of progesterone prevented the increase in these parameters. 80 Endogenous estradiol levels in premenopausal women, however, failed to associate with VLDL-apoB 100 or VLDL-triglyceride production rates. 57…”

“…The addition of progesterone prevented the increase in these parameters. 80 Endogenous estradiol levels in premenopausal women, however, failed to associate with VLDL-apoB 100 or VLDL-triglyceride production rates. 57 During pregnancy, the increase of steroid hormones released by the placenta results in drastic alterations in the circulating lipid profile.…”

Current Diagnosis and Management of Primary Chylomicronemia

“…Plasma TG levels progressively increase in healthy subjects by 2-to 4-fold 67) , and markedly increase in subjects with PCM [68][69][70][71][72][73][74] . Pregnancy increases TGRL (VLDL) production and decreases TGRL clearance [75][76][77][78] .…”