|Lamon-fava, Stefania - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Diffenderfer, Margaret - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Barrett, P. Hugh - University Of Western Australia|
|Wan, Wing Yee - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Postfai, Borbala - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Nartsupha, Chorthip - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Dolnikowski, Gregory - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Schaefer, Ernst - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Lipids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2018
Publication Date: 3/14/2018
Citation: Lamon-Fava, S., Diffenderfer, M.R., Barrett, P.R., Wan, W., Postfai, B., Nartsupha, C., Dolnikowski, G.G., Schaefer, E.J. 2018. Differential effects of estrogen and progestin on apolipoprotein B100 and B48 kinetics in postmenopausal women. Lipids. 53(2):167-175. https://doi.org/10.1002/lipd.12011.
DOI: https://doi.org/10.1002/lipd.12011 Interpretive Summary: Postmenopausal hormonal replacement therapy (HT) has been shown to affect plasma levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), also known as "bad cholesterol." Our study examined the independent mechanisms by which the estrogen and progestin in HT affect TG and LDL-C. We studied the rate of production and clearance of apoB, the protein that carries TG and LDL-C in plasma, in 7 postmenopausal women. Our study indicates that estrogen causes an increase in TG, and this is caused by an increased production of the apo B that carries TG, while progestin counteracts this effect. We also found that estrogen tended to reduce LDL-C, and this was associated with a significant increase in the clearance of apo B in LDL. Progestin also counteracted this effect. Our results indicate that the estrogen and the progestin contained in common post-menopausal hormonal replacement therapy have different and independent effects on lipoproteins that cause cardiovascular disease.
Technical 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/d) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/d) 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 lipoprotein (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.