CoChat
Sign Up
Cited by 1,152Menopause: Health Impacts and TreatmentsLipoproteins and Cardiovascular HealthEstrogen and related hormone effects

Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins.

Open access
Walsh, Brian W., Schiff, Isaac, Rosner, Bernard, Greenberg, Louise, Ravnikar, Veronica, Sacks, Frank M.·1991·New England Journal of Medicine
DOI 10.1056/nejm199110243251702
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Postmenopausal estrogen-replacement therapy may reduce the risk of cardiovascular disease, and this beneficial effect may be mediated in part by favorable changes in plasma lipid levels. However, the effects on plasma lipoprotein levels of postmenopausal estrogens in the low doses currently used have not been precisely quantified, and the mechanism of these effects is unknown. METHODS: We conducted two randomized, double-blind crossover studies in healthy postmenopausal women who had normal lipid values at base line. In study 1, 31 women received placebo and conjugated estrogens at two doses (0.625 mg and 1.25 mg per day), each treatment for three months. In study 2, nine women received placebo, oral micronized estradiol (2 mg per day), and transdermal estradiol (0.1 mg twice a week), each treatment for six weeks. The metabolism of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was measured by endogenously labeling their protein component, apolipoprotein B. RESULTS: In study 1, the conjugated estrogens at doses of 0.625 mg per day and 1.25 mg per day decreased the mean LDL cholesterol level by 15 percent (95 percent confidence interval, 11 to 19 percent; P less than 0.0001) and 19 percent (95 percent confidence interval, 15 to 23 percent; P less than 0.0001), respectively; increased the HDL cholesterol level by 16 percent (95 percent confidence interval, 12 to 20 percent; P less than 0.0001) and 18 percent (95 percent confidence interval, 14 to 22 percent; P less than 0.0001), respectively; and increased VLDL triglyceride levels by 24 percent (95 percent confidence interval, 8 to 40 percent; P less than 0.003) and 42 percent (95 percent confidence interval, 26 to 58 percent; P less than 0.0001), respectively. In study 2, oral estradiol increased the mean concentration of large VLDL apolipoprotein B by 30 +/- 10 percent (P = 0.05) by increasing its production rate by 82 +/- 18 percent (P less than 0.01). Most of this additional large VLDL was cleared directly from the circulation and was not converted to small VLDL or LDL. Oral estradiol reduced LDL cholesterol concentrations by 14 +/- 3 percent (P less than 0.005), because LDL catabolism increased by 36 +/- 7 percent (P less than 0.005). The oral estradiol increased the HDL cholesterol level by 15 +/- 2 percent (P less than 0.0001). Transdermal estradiol had no effect. CONCLUSIONS: The postmenopausal use of oral estrogens in low doses favorably alters LDL and HDL levels that may protect women against atherosclerosis, while minimizing potentially adverse effects on triglyceride levels. The decrease in LDL levels results from accelerated LDL catabolism; the increase in triglyceride levels results from increased production of large, triglyceride-rich VLDL.

Integrity signals

Registry

Crossref · 10.1056/nejm199110243251702

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Oral estrogen in the form of estrogen replacement therapy or oral contraceptives has a triglyceride-increasing effect due to increased hepatic VLDL production; this effect does not occur with transdermal estrogen due to lesser exposure to the liver.

    “Oral estrogen in the form of estrogen replacement therapy or oral contraceptives has a triglyceride-increasing effect due to increased hepatic VLDL production.This effect does not occur with transdermal estrogen due to its lesser exposure to the liver (87, 88).”

    From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [87]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Walsh, B. W., Schiff, I., Rosner, B., Greenberg, L., Ravnikar, V., & Sacks, F. M.
Affiliations
Harvard University (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1991-10-24
Volume
325
Issue
17
Pages
1196-1204
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199110243251702
OpenAlex
W1987144846
Cited by
1,152
References
46
Citations by year
2026: 15 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 15 · 2021: 19 · 2020: 13 · 2019: 11 · 2018: 13 · 2017: 16 · 2016: 16 · 2015: 15 · 2014: 7 · 2013: 15 · 2012: 25
FWCI
32.57
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion)
Funders
  • National Institutes of Health (5r01hl034980-07)
  • National Heart, Lung, and Blood Institute (HL34980)
  • National Center for Research Resources (RR02635, M01RR002635)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
conjugated estrogens, transdermal estradiol, serum lipoproteins, LDL cholesterol, HDL cholesterol, VLDL triglycerides, apolipoprotein B, lipoprotein metabolism, cardiovascular risk, postmenopausal women, dose-response relationship
MeSH terms
Administration, Cutaneous, Administration, Oral, Adult, Apolipoproteins, Arteriosclerosis, Double-Blind Method, Estradiol, Female, Humans, Individuality, Lipoproteins, Lipoproteins, LDL, Lipoproteins, VLDL, Menopause, Middle Aged, Triglycerides, Estrogen Replacement Therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review