Effect of oral estradiol on Lp(a) and other lipoproteins in postmenopausal women. A randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND Lp(a) lipoprotein level is an independent risk factor for premature coronary artery disease and cerebrovascular accident. Concentrations of this lipoprotein tend to increase after menopause. OBJECTIVE To determine whether oral estrogen was effective in lowering concentrations of Lp(a) lipoprotein in postmenopausal women. METHODS A double-blind, placebo-controlled, cross-over study was conducted during a 12-month period in 100 postmenopausal women who had undergone hysterectomy. They were randomized into two groups: group 1 received oral estradiol, 2 mg/d, for the first 6 months and placebo for the second, and group 2 received these treatments in the reverse order. After completion of the crossover study, the effect of prolonged administration of oral estradiol was examined by placing all patients on active treatment and repeating the lipoprotein measurements approximately 12 months later. RESULTS No significant differences were noted between the two groups at the commencement of the study (median concentration of Lp[a] lipoprotein, 10.78 mg/dL [range, 2.2 to 108.5 mg/dL] in group 1 and 12.74 mg/dL [range, 0.8 to 98.1 mg/dL] in group 2). Crossover analysis showed a 9.62% reduction in values of Lp(a) lipoprotein with estradiol treatment compared with placebo during 12 months of treatment (P < .001). With prolonged treatment, the median concentration of Lp(a) lipoprotein for those in group 1 decreased from 8.12 mg/dL (range, 1.05 to 57.4 mg/dL) to 5.77 mg/dL (range, 0.84 to 75.39 mg/dL) (P < .001). In group 2, the median concentration decreased from 8.19 mg/dL (range, 2.52 to 99.82 mg/dL) to 7.07 mg/dL (range, 0.70 to 48.79 mg/dL), but this difference was not significant (P = .63). CONCLUSIONS The results of this study confirm the beneficial effect of oral estradiol on the basic lipoprotein pattern and demonstrate that this treatment is effective in reducing concentrations of Lp(a) lipoprotein in postmenopausal women.

[1]  W. Kannel,et al.  Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. , 2020, Annals of internal medicine.

[2]  B. Tomlinson,et al.  The effect of percutaneous oestrogen replacement therapy on Lp(a) and other lipoproteins. , 1995, Maturitas.

[3]  D. Illingworth,et al.  Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial. , 1994, Archives of internal medicine.

[4]  F. Sacks,et al.  Effect of postmenopausal estrogen replacement on plasma Lp(a) lipoprotein concentrations. , 1994, Archives of internal medicine.

[5]  Y. Min,et al.  Effects of hormone replacement therapy on lipoprotein(a) and lipids in postmenopausal women. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[6]  M. Whitehead,et al.  Effect of Continuous Combined Estrogen and Desogestrel Hormone Replacement Therapy on Serum Lipids and Lipoproteins , 1994, Obstetrics and gynecology.

[7]  G. Tomkin,et al.  Altered Regulation of Cholesterol Metabolism in Type I Diabetic Women During the Menstrual Cycle , 1993, Diabetic medicine : a journal of the British Diabetic Association.

[8]  P. Crosignani,et al.  The lowering of lipoprotein[a] induced by estrogen plus progesterone replacement therapy in postmenopausal women. , 1993, Archives of internal medicine.

[9]  J. Beaumont,et al.  Lp(a) levels and antiestrogen antibodies in women with and without thrombosis in the course of oral contraception. , 1993, Atherosclerosis.

[10]  A. Folsom,et al.  Association of Hormone-Replacement Therapy with Various Cardiovascular Risk Factors in Postmenopausal Women , 1993 .

[11]  P. Demacker,et al.  Beneficial effects on serum lipoproteins by 17 beta-oestradiol-dydrogesterone therapy in postmenopausal women; a prospective study. , 1992, European journal of obstetrics, gynecology, and reproductive biology.

[12]  B. Wren The effect of oestrogen on the female cardiovascular system , 1992, The Medical journal of Australia.

[13]  T. Montine,et al.  Massive pulmonary embolus and anabolic steroid abuse. , 1992, JAMA.

[14]  T. Kobayashi,et al.  Reduction of serum lipoprotein(a) using estrogen in a man with familial hypercholesterolemia. , 1992, JAMA.

[15]  B. Angelin,et al.  Hormonal regulation of serum Lp (a) levels. Opposite effects after estrogen treatment and orchidectomy in males with prostatic carcinoma. , 1992, The Journal of clinical investigation.

[16]  L. Bernstein,et al.  Lp(a) lipoprotein: Relationship to cardiovascular disease risk factors, exercise and estrogen , 1992, American journal of obstetrics and gynecology.

[17]  K. Anderson,et al.  Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease. , 1992, Journal of the American College of Cardiology.

[18]  M. Panteghini,et al.  Serum concentrations of lipoprotein(a) during normal pregnancy and postpartum. , 1991, Clinical Chemistry.

[19]  G. Hortin,et al.  Cross-reactivity of a vancomycin degradation product in three immunoassays of vancomycin. , 1991, Clinical chemistry.

[20]  J. F. Barnes,et al.  Lipoprotein (a) concentrations in postmenopausal women taking norethisterone. , 1991, BMJ.

[21]  W. Willett,et al.  A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. , 1991, The New England journal of medicine.

[22]  S. Haffner,et al.  Decrease of Lipoprotein(a) With Improved Glycemic Control in IDDM Subjects , 1991, Diabetes Care.

[23]  L. Levitsky,et al.  Lipoprotein(a) Levels in Black and White Children and Adolescents With IDDM , 1991, Diabetes Care.

[24]  A. Silman,et al.  Observer agreement of categorical assessments , 1991, The Lancet.

[25]  P. Crosignani,et al.  Plasma Lp(a) concentration after oestrogen and progestagen in postmenopausal women , 1991, The Lancet.

[26]  J. Woo,et al.  Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. , 1991, Stroke.

[27]  J. Larosa,et al.  Effects of Conjugated Equine Estrogen With and Without Three Different Progestogens on Lipoproteins, High-Density Lipoprotein Subfractions, and Apolipoprotein A-I , 1991, Obstetrics and gynecology.

[28]  A. Hamsten,et al.  Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid , 1989, Journal of internal medicine.

[29]  A. Benadé,et al.  Serum lipoprotein effects of conjugated estrogen and a sequential conjugated estrogen-medrogestone regimen in hysterectomized postmenopausal women , 1989 .

[30]  J. Fruchart,et al.  Lp(a) lipoprotein in patients with chronic renal failure treated by hemodialysis. , 1987, Clinical chemistry.

[31]  W. Willett,et al.  Menopause and the risk of coronary heart disease in women. , 1987, The New England journal of medicine.

[32]  N. Morton,et al.  Lp(a) lipoprotein as a risk factor for myocardial infarction. , 1986, JAMA.

[33]  A. Gotto,et al.  CORONARY ARTERY DISEASE Association of levels of lipoprotein Lp ( a ) , plasma lipids , and other lipoproteins with coronary artery disease documented by angiography , 2022 .

[34]  K. Pfeiffer,et al.  Fluctuations of plasma liproprotein-a concentrations during pregnancy and post partum , 1986 .

[35]  R. Lobo,et al.  Comparison of Lipid and Androgen Levels After Conjugated Estrogen or Depo- Medroxyprogesterone Acetate Treatment in Postmenopausal Women , 1985, Obstetrics and Gynecology.

[36]  W. Hazzard,et al.  Reduction of lecithin-cholesterol acyltransferase, apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid stanozolol. , 1984, Biochimica et biophysica acta.

[37]  E. Barrett-Connor,et al.  Estrogen use and all-cause mortality. Preliminary results from the Lipid Research Clinics Program Follow-Up Study. , 1983, JAMA.

[38]  M. Hills,et al.  The Two‐Period Crossover Trial , 1982 .

[39]  K. Berg,et al.  Lp(a) lipoprotein enters cultured fibroblasts independently of the plasma membrane low density lipoprotein receptor , 1981, Clinical genetics.

[40]  C. Florén,et al.  Uptake of Lp (a) lipoprotein by cultured fibroblasts. , 1981, Biochemical and biophysical research communications.

[41]  D. Jacobs,et al.  Lipoprotein‐Cholesterol Distributions in Selected North American Populations: The Lipid Research Clinics Program Prevalence Study , 1980, Circulation.

[42]  M C Hjortland,et al.  High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. , 1977, The American journal of medicine.

[43]  W. Kannel,et al.  Some atherogenic concomitants of menopause: The Framingham Study. , 1976, American journal of epidemiology.

[44]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[45]  W Young,et al.  Ischemic Heart Disease, Atherosclerosis, and Longevity , 1966, Circulation.

[46]  W. März,et al.  Effect on lipid metabolism of a biphasic desogestrel-containing oral contraceptive: divergent changes in apolipoprotein B and E and transitory decrease in Lp(a) levels. , 1993, Contraception.

[47]  M. Seed,et al.  Lipoprotein Lp(a) levels are reduced by danazol, an anabolic steroid. , 1992, Atherosclerosis.

[48]  M. Sandkamp Chapter 14 – Lipoprotein(a) in PROCAM Participants and Young Myocardial Infarction Survivors , 1990 .

[49]  H. Brewer Chapter 15 – Effectiveness of Diet and Drugs in the Treatment of Patients with Elevated Lp(a) Levels , 1990 .

[50]  J. Poloniecki,et al.  The Two Period Cross Over Trial , 1982 .

[51]  E Marth,et al.  Lipoprotein Lp(a) and the risk for myocardial infarction. , 1981, Atherosclerosis.