Background Postmenopausal estrogen therapy has favorable effectson serum lipoproteins in women with normal serum lipid levels,but the effect of combined estrogen and progestin therapy onlipoproteins in women with hypercholesterolemia has not beendetermined, nor has it been directly compared with the effectof conventional lipid-lowering therapy.
Methods In a randomized crossover trial, we studied 58 postmenopausalwomen with fasting serum total cholesterol levels greater than250 mg per deciliter. Each woman received simvastatin (10 mgdaily) for eight weeks and postmenopausal hormone therapy (upto 1.25 mg of conjugated equine estrogens daily, along with5 mg of medroxyprogesterone acetate daily) for eight weeks,with an eight-week washout period between the two treatmentphases.
Results At base line, the mean (±SD) cholesterol valueswere as follows: total cholesterol, 305±39 mg per deciliter;high-density lipoprotein (HDL) cholesterol, 62±19 mgper deciliter; and low-density lipoprotein (LDL) cholesterol,217±39 mg per deciliter. For total cholesterol, the meandecrease with hormone therapy was 14 percent (95 percent confidenceinterval, 11 to 16 percent) and the mean decrease with simvastatinwas 26 percent (95 percent confidence interval, 23 to 29 percent).For LDL cholesterol, the mean decrease was 24 percent (95 percentconfidence interval, 20 to 28 percent) with hormone therapyand 36 percent (95 percent confidence interval, 32 to 40 percent)with simvastatin. The effect of simvastatin was significantlygreater than that of hormone therapy (P<0.001). HDL cholesterolincreased similarly with hormone therapy (mean increase, 7 percent;95 percent confidence interval, 2 to 12 percent) and simvastatin(mean increase, 7 percent; 95 percent confidence interval, 4to 10 percent). Triglyceride levels increased with hormone therapy(mean increase, 29 percent; 95 percent confidence interval,15 to 42 percent) but decreased with simvastatin (mean decrease,14 percent; 95 percent confidence interval, 8 to 20 percent).Lp(a) lipoprotein decreased with hormone therapy (mean decrease,27 percent; 95 percent confidence interval, 20 to 34 percent),but not with simvastatin.
Conclusions In postmenopausal women with hypercholesterolemia,therapy with estrogen plus progestin has beneficial effectson lipoprotein levels. Hormone therapy may be an effective alternativeto treatment with simvastatin, especially in women with normaltriglyceride levels.
Source Information
From the Jean Hailes Foundation (G.M.D., S.R.D.); the Department of Cardiology, Austin and Repatriation Medical Centre (G.M.D., J.A.J.); and the Department of Mathematics, Monash University (P.I.M.) — all in Melbourne, Victoria, Australia.
Address reprint requests to Dr. Darling at the Jean Hailes Foundation, 291 Clayton Rd., Clayton, Victoria 3168, Australia.
The ESHRE Capri Workshop Group,
(2006). Hormones and cardiovascular health in women. Hum Reprod Update
12: 483-497
[Abstract][Full Text]
Holmes, D. T., Schick, B. A., Humphries, K. H., Frohlich, J.
(2005). Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia. Clin. Chem.
51: 2067-2073
[Abstract][Full Text]
Davis, S R, Dinatale, I, Rivera-Woll, L, Davison, S
(2005). Postmenopausal hormone therapy: from monkey glands to transdermal patches. J Endocrinol
185: 207-222
[Abstract][Full Text]
Liu, L., Zhao, S.-P., Cheng, Y.-C., Li, Y.-L.
(2003). Xuezhikang Decreases Serum Lipoprotein(a) and C-reactive Protein Concentrations in Patients with Coronary Heart Disease. Clin. Chem.
49: 1347-1352
[Abstract][Full Text]
Davison, S., Davis, S. R.
(2003). New Markers for Cardiovascular Disease Risk in Women: Impact of Endogenous Estrogen Status and Exogenous Postmenopausal Hormone Therapy. J. Clin. Endocrinol. Metab.
88: 2470-2478
[Abstract][Full Text]
Kuller, L. H.
(2003). Hormone Replacement Therapy and Risk of Cardiovascular Disease: Implications of the Results of the Women's Health Initiative. Arterioscler. Thromb. Vasc. Bio.
23: 11-16
[Abstract][Full Text]
Evans, M. J., Harris, H. A., Miller, C. P., Karathanasis, S. K., Adelman, S. J.
(2002). Estrogen Receptors {alpha} and {beta} Have Similar Activities in Multiple Endothelial Cell Pathways. Endocrinology
143: 3785-3795
[Abstract][Full Text]
Prati, D., Taioli, E., Zanella, A., Torre, E. D., Butelli, S., Del Vecchio, E., Vianello, L., Zanuso, F., Mozzi, F., Milani, S., Conte, D., Colombo, M., Sirchia, G.
(2002). Updated Definitions of Healthy Ranges for Serum Alanine Aminotransferase Levels. ANN INTERN MED
137: 1-10
[Abstract][Full Text]
Mikkola, T. S, Clarkson, T. B
(2002). Estrogen replacement therapy, atherosclerosis, and vascular function. Cardiovasc Res
53: 605-619
[Abstract][Full Text]
Teede, H. J., Dalais, F. S., Kotsopoulos, D., Liang, Y.-L., Davis, S., McGrath, B. P.
(2001). Dietary Soy Has Both Beneficial and Potentially Adverse Cardiovascular Effects: A Placebo-Controlled Study in Men and Postmenopausal Women. J. Clin. Endocrinol. Metab.
86: 3053-3060
[Abstract][Full Text]
Naessen, T., Rodriguez-Macias, K., Lithell, H.
(2001). Serum Lipid Profile Improved by Ultra-Low Doses of 17{beta}-Estradiol in Elderly Women. J. Clin. Endocrinol. Metab.
86: 2757-2762
[Abstract][Full Text]
Jones, M. E. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., Simpson, E. R.
(2000). Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc. Natl. Acad. Sci. USA
97: 12735-12740
[Abstract][Full Text]
Park, J. S., Jung, H. H., Yang, W. S., Kim, S. B., Min, W. K., Chi, H. S.
(2000). Effects of hormonal replacement therapy on lipid and haemostatic factors in post-menopausal ESRD patients. Nephrol Dial Transplant
15: 1835-1840
[Abstract][Full Text]
Mosca, L.
(2000). The Role of Hormone Replacement Therapy in the Prevention of Postmenopausal Heart Disease. Arch Intern Med
160: 2263-2272
[Abstract][Full Text]
Shlipak, M. G., Simon, J. A., Vittinghoff, E., Lin, F., Barrett-Connor, E., Knopp, R. H., Levy, R. I., Hulley, S. B.
(2000). Estrogen and Progestin, Lipoprotein(a), and the Risk of Recurrent Coronary Heart Disease Events After Menopause. JAMA
283: 1845-1852
[Abstract][Full Text]
Wight, E., Kung, C. F., Moreau, P., Takase, H., Bersinger, N. A., Luscher, T. F.
(2000). Aging, Serum Estradiol Levels, and Pregnancy Differentially Affect Vascular Reactivity of the Rat Uterine Artery. Reproductive Sciences
7: 106-113
[Abstract]
Fak, A.S, Erenus, M, Tezcan, H, Caymaz, O, AtagunduZ, P, Oktay, S, Oktay, A
(2000). Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on serum lipid levels in hypercholesterolaemic post-menopausal women. Eur Heart J
21: 190-197
[Abstract]
Brehme, U., Bruck, B., Gugel, N., Wehrmann, M., Hanke, S., Finking, G., Schmahl, F. W., Hanke, H.
(1999). Aortic Plaque Size and Endometrial Response in Cholesterol-Fed Rabbits Treated With Estrogen Plus Continuous or Sequential Progestin. Arterioscler. Thromb. Vasc. Bio.
19: 1930-1937
[Abstract][Full Text]
Pinkerton, J. V., Santen, R.
(1999). Alternatives to the Use of Estrogen in Postmenopausal Women. Endocr. Rev.
20: 308-320
[Abstract][Full Text]
Herrington, D. M., Werbel, B. L., Riley, W. A., Pusser, B. E., Morgan, T. M.
(1999). Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease. J Am Coll Cardiol
33: 2030-2037
[Abstract][Full Text]
Harper, C. R., Jacobson, T. A.
(1999). New Perspectives on the Management of Low Levels of High-Density Lipoprotein Cholesterol. Arch Intern Med
159: 1049-1057
[Abstract][Full Text]
Koh, K. K., Cardillo, C., Bui, M. N., Hathaway, L., Csako, G., Waclawiw, M. A., Panza, J. A., Cannon, R. O. III
(1999). Vascular Effects of Estrogen and Cholesterol-Lowering Therapies in Hypercholesterolemic Postmenopausal Women. Circulation
99: 354-360
[Abstract][Full Text]
Sbarouni, E., Kyriakides, Z. S., Kremastinos, D. T.
(1998). The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease. J Am Coll Cardiol
32: 1244-1250
[Abstract][Full Text]
McCredie, R. J., McCrohon, J. A., Turner, L., Griffiths, K. A., Handelsman, D. J., Celermajer, D. S.
(1998). Vascular reactivity is impaired in genetic females taking high-dose androgens. J Am Coll Cardiol
32: 1331-1335
[Abstract][Full Text]
Su, W., Campos, H., Judge, H., Walsh, B. W., Sacks, F. M.
(1998). Metabolism of Apo(a) and ApoB100 of Lipoprotein(a) in Women: Effect of Postmenopausal Estrogen Replacement. J. Clin. Endocrinol. Metab.
83: 3267-3276
[Abstract][Full Text]
(1998). Treatment of Estrogen Deficiency Symptoms in Women Surviving Breast Cancer. J. Clin. Endocrinol. Metab.
83: 1993-2000
[Full Text]
Simpson, E.
(1998). Why Do the Clinical Sequelae of Estrogen Deficiency Affect Women More than Men?a. J. Clin. Endocrinol. Metab.
83: 2214-2215
[Full Text]
Pines, A., Levo, Y., Ayalon, D., Cashin-Hemphill, L., Vailas, L. I., Darling, G. M., Davis, S., Johns, J. A.
(1998). Hormone-Replacement Therapy Compared with Simvastatin for Postmenopausal Women with Hypercholesterolemia. NEJM
338: 63-64
[Full Text]
(1997). HORMONE THERAPY VS. SIMVASTATIN FOR HYPERCHOLESTEROLEMIA IN WOMEN. JWatch General
1997: 3-3
[Full Text]
Previous
