Effects of low dosage progestin-only administration upon plasma triglycerides and lipoprotein metabolism in postmenopausal women.

Wolfe, Benjamin; Huff, Murray W.

doi:10.1172/jci116588

Cited by 17 publications

(6 citation statements)

References 42 publications

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“…Wolfe & Huff [45] observed reduced LDL production and LDL apoB pool size without changes in the LDL clearance rate in postmenopausal women treated with combined oral 17-oestradiol and dl-norgestrel. They have also found that progestin administration alone increases LDL apoB production, but this effect is compensated for by a concomitant increase in the fractional catabolic rate of LDL apoB, resulting in an unchanged LDL apoB pool size [46]. Consistent with these previous findings in the transdermal group, no further alterations were observed in the density distribution and composition of LDL during the MPA phase compared with the oestrogenalone phase.…”

Section: Discussionsupporting

confidence: 68%

Different effects of continuous oestrogen–progestin and transdermal oestrogen with cyclic progestin regimens on low‐density lipoprotein subclasses

Tilly-Kiesi

Lappi

Puolakka

et al. 1996

Eur J Clin Investigation

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Seventy-five postmenopausal women were randomly allocated to receive either continuous oral 17 beta-oestradiol 2 mg day-1 and norethisterone acetate 1 mg day-1 (E2/NETA) or transdermal treatment consisting of 28-day cycles with patches delivering 17 beta-oestradiol 50 micrograms day-1 combined with oral cyclic medroxyprogesterone acetate 10 mg day-1, on days 17-28 (E2/MPA). At baseline, the plasma lipid and lipoprotein concentrations, composition and concentrations of low-density lipoprotein (LDL) subclasses (LDL1, LDL2 and LDL3) isolated by density-gradient ultracentrifugation were similar in the two groups. The post-heparin plasma hepatic lipase activity (HL) correlated inversely with the percentage of total LDL found in LDL1 (buoyant LDL) and directly with the percentage of LDL found in LDL3 (dense LDL). After 12 months of hormone replacement therapy (HRT), the total and LDL-cholesterol concentration of the E2/ NETA group decreased by 14% and 17% respectively (P < 0.001), while in the E2/MPA group these parameters remained unchanged. The lowering of LDL-cholesterol in the E2/NETA group was a consequence of a significant reduction of the large, buoyant LDL particles (LDL1) from 103 mg dL-1 to 60 mg dl-1 (P < 0.001) and of a decrease of cholesterol content of LDL particles in the major LDL subclass, LDL2. In the E2/MPA group, the concentration of LDL1 decreased, but less than in the oral group. In both groups, a significant increase in the concentration of the LDL3 subclass was observed, indicating an overall shift to denser LDL particles. After 12 months, the post-heparin plasma HL activity decreased only in the E2/NETA group (by 12%). The inverse correlation between post-heparin plasma HL activity and LDL1 persisted in both groups, but the direct correlation between HL and LDL3 vanished in the E2/NETA group and subsided in the E2/MPA group. Our results indicate that HRT has multiple effects on LDL subclasses and suggest that these changes cannot be explained by changes in HL activity.

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Section: Discussionsupporting

confidence: 68%

Different effects of continuous oestrogen–progestin and transdermal oestrogen with cyclic progestin regimens on low‐density lipoprotein subclasses

Tilly-Kiesi

Lappi

Puolakka

et al. 1996

Eur J Clin Investigation

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“…In one, progestin had no effect on the efficiency of VLDL-apoB-100 removal in postmenopausal women (60). In another, cross-sectional study, oral contraceptives, containing progestins only or estrogens plus progestins, were associated with higher endogenous and exogenous TG removal from plasma compared with no treatment or estrogens alone (28).…”

Section: Discussionmentioning

confidence: 96%

“…15 and 48). Oral estrogen administration increases VLDL-TG and VLDL-apoB-100 secretion and concentration in plasma (9,15,48), whereas oral administration of progestins elicits the opposite effect and lowers VLDL-TG and VLDL-apoB-100 concentrations and VLDL-apoB-100 secretion (15,48,60), although it apparently has no effect on VLDL-TG secretion (28). The difference between these findings and ours may be due to differences in the amount of sex hormones available: exogenous hormone administration in the earlier published studies resulted in relatively high, steady hormone concentrations in the systemic circulation that were maintained for several weeks.…”

Section: Discussionmentioning

confidence: 99%

No effect of menstrual cycle phase on basal very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics

Magkos¹,

Patterson²,

Mittendorfer³

2006

American Journal of Physiology-Endocrinology and Metabolism

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(TG), increased total and LDL-cholesterol concentrations and decreased HDL-cholesterol concentration, is an important risk factor for cardiovascular disease. Premenopausal women have a less atherogenic plasma lipid profile and a lower risk of cardiovascular disease than men, but this female advantage disappears after menopause. This suggests that female sex steroids affect lipoprotein metabolism. The impact of variations in the availability of ovarian hormones during the menstrual cycle on lipoprotein metabolism is not known. We therefore investigated whether very-low-density lipoprotein (VLDL)-TG and VLDL-apolipoprotein B-100 (apoB-100) kinetics are different during the follicular (FP) and luteal phases (LP) of the menstrual cycle. We studied seven healthy, premenopausal women (age 27 Ϯ 2 yr, BMI 25 Ϯ 2 kg/m 2 ) once during FP and once during LP. We measured VLDL-TG, VLDL-apoB-100, and plasma free fatty acid (FFA) kinetics by using stable isotope-labeled tracers, VLDL subclass profile by nuclear magnetic resonance spectroscopy, whole body fat oxidation by indirect calorimetry, and the plasma concentrations of lipoprotein lipase (LPL) and hepatic lipase (HL) by ELISA. VLDL-TG and VLDLapoB-100 concentrations in plasma, VLDL-TG and VLDL-apoB-100 secretion rates and mean residence times, VLDL subclass distribution, FFA concentration and rate of appearance in plasma, whole body substrate oxidation, and LPL and HL concentrations in plasma were not different during the FP and the LP. We conclude that VLDL-TG and VLDL-apoB-100 metabolism is not affected by menstrual cycle phase. sex hormones; stable isotope; lipid DYSLIPIDEMIA, characterized by increased plasma triglyceride (TG), increased total and LDL-cholesterol, and reduced HDLcholesterol concentrations, is a major risk factor for cardiovascular disease (41). Premenopausal women have a lesser risk of developing cardiovascular disease than age-matched men, but the "female advantage" disappears after menopause (26). Differences in plasma lipid concentrations, particularly plasma TG concentration, between men and women and pre-and postmenopausal women are likely responsible for this phenomenon. The increase in cardiovascular disease risk resulting from a given rise in plasma TG concentration is more than twofold higher for women than for men (23). Premenopausal women have lower plasma TG concentration than men (55); this difference between the sexes is abolished after menopause because of an increase in plasma TG concentration that coincides with the onset of menopause (10). This suggests a beneficial effect of ovarian hormones on plasma TG metabolism. Findings from studies in postmenopausal women receiving hormone replacement therapy and premenopausal women taking hormonal contraceptives indicate that this is likely due to the lack of progesterone rather than estradiol.Hormone replacement therapy providing progestins alone to postmenopausal women decreases fasting plasma TG concentration, whereas estrogens increase fasting plasma TG concentration (19). Also, estroge...

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“…In addition, estrogen administration in rats reduces the expression of the HDL receptor, scavenger receptor class B type I (SR‐B1) on liver cells (for a review see Ref [42]). In contrast to estrogens, androgens are known to inhibit the VLDL triglyceride synthesis [20, 21], whereas they increase HL activity [23, 24] and consequently lower HDL cholesterol levels [22, 43].…”

Section: Discussionmentioning

confidence: 99%

“…VLDL metabolism is strongly in¯uenced by estrogens and androgens, the former enhancing the VLDL triglyceride synthesis in the liver [18,19] and the latter decreasing it [20,21]. Estrogens inhibit hepatic lipase (HL) activity [22,23], whereas androgens have a stimulating effect [23,24].…”

Section: Introductionmentioning

confidence: 99%

The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia

Beer

Smelt

Vark

et al. 2002

Journal of Internal Medicine

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Objective. To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP). Design and intervention. Patients were randomized to receive, in a double-blind cross-over fashion, a ®xed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements. Setting. The Leiden University Medical Center. Subjects. Postmenopausal women with type III HLP (aged £65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the ®ve included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L ±1 . Main outcome measures. A signi®cant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels. Results. Plasma triglyceride and total cholesterol levels decreased from 6.82 3.58 to 2.45 1.36 mmol L ±1 and from 13.53 3.64 to 6.61 2.03 mmol L ±1 , respectively (both P < 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased signi®cantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P < 0.05). Conclusions. Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.

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Effects of low dosage progestin-only administration upon plasma triglycerides and lipoprotein metabolism in postmenopausal women.

Cited by 17 publications

References 42 publications

Different effects of continuous oestrogen–progestin and transdermal oestrogen with cyclic progestin regimens on low‐density lipoprotein subclasses

Different effects of continuous oestrogen–progestin and transdermal oestrogen with cyclic progestin regimens on low‐density lipoprotein subclasses

No effect of menstrual cycle phase on basal very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics

The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia

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