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Transactions of the American Clinical and Climatological Association logoLink to Transactions of the American Clinical and Climatological Association
. 1990;101:168–189.

Why women live longer than men: the biologic mechanism of the sex differential in longevity.

W R Hazzard 1, D Applebaum-Bowden 1
PMCID: PMC2376508  PMID: 2486441

Abstract

1. Exogenous sex steroids appear to influence lipoproteins in a manner that is a caricature of the effects of endogenous sex steroids: Estrogens raise HDL (selectively HDL2) and lower LDL; Androgens lower HDL (selectively HDL2), while raising LDL. 2. Exogenous sex steroids are likely to affect LDL metabolism via effects on the LDL receptor; Estrogens increase LDL receptor activity (in non-human species at both the hepatic cellular and mRNA levels, though this is yet to be confirmed in humans); ??Androgens decrease LDL receptor activity (yet to be tested in either human or non-human species). 3. Exogenous sex steroids appear to alter HDL levels predominantly via modulation of HDL catabolism; Estrogens retard HDL catabolism (33) (and may also increase apo A-I synthesis and HDL production); Androgens accelerate HDL catabolism (30). 4. Modulation of HDL (and possibly LDL) metabolism by sex steroids may be mediated by alterations in hepatic triglyceride lipase (HTGL) activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Applebaum-Bowden D., Haffner S. M., Hazzard W. R. The dyslipoproteinemia of anabolic steroid therapy: increase in hepatic triglyceride lipase precedes the decrease in high density lipoprotein2 cholesterol. Metabolism. 1987 Oct;36(10):949–952. doi: 10.1016/0026-0495(87)90130-2. [DOI] [PubMed] [Google Scholar]
  2. Bradley D. D., Wingerd J., Petitti D. B., Krauss R. M., Ramcharan S. Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins. N Engl J Med. 1978 Jul 6;299(1):17–20. doi: 10.1056/NEJM197807062990104. [DOI] [PubMed] [Google Scholar]
  3. Bush T. L., Barrett-Connor E., Cowan L. D., Criqui M. H., Wallace R. B., Suchindran C. M., Tyroler H. A., Rifkind B. M. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation. 1987 Jun;75(6):1102–1109. doi: 10.1161/01.cir.75.6.1102. [DOI] [PubMed] [Google Scholar]
  4. Chesnut C. H., 3rd, Ivey J. L., Gruber H. E., Matthews M., Nelp W. B., Sisom K., Baylink D. J. Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action. Metabolism. 1983 Jun;32(6):571–580. doi: 10.1016/0026-0495(83)90027-6. [DOI] [PubMed] [Google Scholar]
  5. Cheung M. C., Albers J. J., Wahl P. W., Hazzard W. R. High density lipoproteins during hypolipidemic therapy. A comparative study of four drugs. Atherosclerosis. 1980 Mar;35(3):215–228. doi: 10.1016/0021-9150(80)90121-5. [DOI] [PubMed] [Google Scholar]
  6. Fries J. F. Aging, natural death, and the compression of morbidity. N Engl J Med. 1980 Jul 17;303(3):130–135. doi: 10.1056/NEJM198007173030304. [DOI] [PubMed] [Google Scholar]
  7. Fries J. F., Green L. W., Levine S. Health promotion and the compression of morbidity. Lancet. 1989 Mar 4;1(8636):481–483. doi: 10.1016/s0140-6736(89)91376-7. [DOI] [PubMed] [Google Scholar]
  8. Godsland I. F., Wynn V., Crook D., Miller N. E. Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions. Am Heart J. 1987 Dec;114(6):1467–1503. doi: 10.1016/0002-8703(87)90552-7. [DOI] [PubMed] [Google Scholar]
  9. Haffner S. M., Kushwaha R. S., Foster D. M., Applebaum-Bowden D., Hazzard W. R. Studies on the metabolic mechanism of reduced high density lipoproteins during anabolic steroid therapy. Metabolism. 1983 Apr;32(4):413–420. doi: 10.1016/0026-0495(83)90052-5. [DOI] [PubMed] [Google Scholar]
  10. Hazzard W. R. Biological basis of the sex differential in longevity. J Am Geriatr Soc. 1986 Jun;34(6):455–471. doi: 10.1111/j.1532-5415.1986.tb03414.x. [DOI] [PubMed] [Google Scholar]
  11. Hazzard W. R., Haffner S. M., Kushwaha R. S., Applebaum-Bowden D., Foster D. M. Preliminary report: kinetic studies on the modulation of high-density lipoprotein, apolipoprotein, and subfraction metabolism by sex steroids in a postmenopausal woman. Metabolism. 1984 Sep;33(9):779–784. doi: 10.1016/0026-0495(84)90102-1. [DOI] [PubMed] [Google Scholar]
  12. Hirvonen E., Mälkönen M., Manninen V. Effects of different progestogens on lipoproteins during postmenopausal replacement therapy. N Engl J Med. 1981 Mar 5;304(10):560–563. doi: 10.1056/NEJM198103053041002. [DOI] [PubMed] [Google Scholar]
  13. Holden C. Can smoking explain ultimate gender gap? Science. 1983 Sep 9;221(4615):1034–1034. doi: 10.1126/science.6879202. [DOI] [PubMed] [Google Scholar]
  14. Knopp R. H., Walden C. E., Wahl P. W., Hoover J. J., Warnick G. R., Albers J. J., Ogilvie J. T., Hazzard W. R. Oral contraceptive and postmenopausal estrogen effects on lipoprotein triglyceride and cholesterol in an adult female population: relationships to estrogen and progestin potency. J Clin Endocrinol Metab. 1981 Dec;53(6):1123–1132. doi: 10.1210/jcem-53-6-1123. [DOI] [PubMed] [Google Scholar]
  15. Ma P. T., Yamamoto T., Goldstein J. L., Brown M. S. Increased mRNA for low density lipoprotein receptor in livers of rabbits treated with 17 alpha-ethinyl estradiol. Proc Natl Acad Sci U S A. 1986 Feb;83(3):792–796. doi: 10.1073/pnas.83.3.792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Matthews K. A., Meilahn E., Kuller L. H., Kelsey S. F., Caggiula A. W., Wing R. R. Menopause and risk factors for coronary heart disease. N Engl J Med. 1989 Sep 7;321(10):641–646. doi: 10.1056/NEJM198909073211004. [DOI] [PubMed] [Google Scholar]
  17. McMillen M. M. Differential mortality by sex in fetal and neonatal deaths. Science. 1979 Apr 6;204(4388):89–91. doi: 10.1126/science.571144. [DOI] [PubMed] [Google Scholar]
  18. Miller N. E., Thelle D. S., Forde O. H., Mjos O. D. The Tromsø heart-study. High-density lipoprotein and coronary heart-disease: a prospective case-control study. Lancet. 1977 May 7;1(8019):965–968. doi: 10.1016/s0140-6736(77)92274-7. [DOI] [PubMed] [Google Scholar]
  19. Musliner T. A., Herbert P. N., Kingston M. J. Lipoprotein substrates of lipoprotein lipase and hepatic triacylglycerol lipase from human post-heparin plasma. Biochim Biophys Acta. 1979 Nov 21;575(2):277–288. doi: 10.1016/0005-2760(79)90029-8. [DOI] [PubMed] [Google Scholar]
  20. ROCKSTEIN M., LIEBERMAN H. M. A life table for the common house fly, Musca domestica. Gerontologia. 1959;3:23–36. doi: 10.1159/000210828. [DOI] [PubMed] [Google Scholar]
  21. RUSS E. M., EDER H. A., BARR D. P. Influence of gonadal hormones on protein-lipid relationships in human plasma. Am J Med. 1955 Jul;19(1):4–24. doi: 10.1016/0002-9343(55)90270-9. [DOI] [PubMed] [Google Scholar]
  22. Ross R. K., Paganini-Hill A., Mack T. M., Arthur M., Henderson B. E. Menopausal oestrogen therapy and protection from death from ischaemic heart disease. Lancet. 1981 Apr 18;1(8225):858–860. doi: 10.1016/s0140-6736(81)92138-3. [DOI] [PubMed] [Google Scholar]
  23. Shirai K., Barnhart R. L., Jackson R. L. Hydrolysis of human plasma high density lipoprotein 2- phospholipids and triglycerides by hepatic lipase. Biochem Biophys Res Commun. 1981 May 29;100(2):591–599. doi: 10.1016/s0006-291x(81)80217-3. [DOI] [PubMed] [Google Scholar]
  24. Stampfer M. J., Willett W. C., Colditz G. A., Rosner B., Speizer F. E., Hennekens C. H. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med. 1985 Oct 24;313(17):1044–1049. doi: 10.1056/NEJM198510243131703. [DOI] [PubMed] [Google Scholar]
  25. Taggart H. M., Applebaum-Bowden D., Haffner S., Warnick G. R., Cheung M. C., Albers J. J., Chestnut C. H., 3rd, Hazzard W. R. Reduction in high density lipoproteins by anabolic steroid (stanozolol) therapy for postmenopausal osteoporosis. Metabolism. 1982 Nov;31(11):1147–1152. doi: 10.1016/0026-0495(82)90166-4. [DOI] [PubMed] [Google Scholar]
  26. Wahl P., Walden C., Knopp R., Hoover J., Wallace R., Heiss G., Rifkind B. Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol. N Engl J Med. 1983 Apr 14;308(15):862–867. doi: 10.1056/NEJM198304143081502. [DOI] [PubMed] [Google Scholar]
  27. Wallentin L., Larsson-Cohn U. Metabolic and hormonal effects of post-menopausal oestrogen replacement treatment. II. Plasma lipids. Acta Endocrinol (Copenh) 1977 Nov;86(3):597–607. doi: 10.1530/acta.0.0860597. [DOI] [PubMed] [Google Scholar]
  28. Wilson P. W., Garrison R. J., Castelli W. P. Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. The Framingham Study. N Engl J Med. 1985 Oct 24;313(17):1038–1043. doi: 10.1056/NEJM198510243131702. [DOI] [PubMed] [Google Scholar]
  29. Windler E. E., Kovanen P. T., Chao Y. S., Brown M. S., Havel R. J., Goldstein J. L. The estradiol-stimulated lipoprotein receptor of rat liver. A binding site that membrane mediates the uptake of rat lipoproteins containing apoproteins B and E. J Biol Chem. 1980 Nov 10;255(21):10464–10471. [PubMed] [Google Scholar]
  30. Wingard D. L. The sex differential in morbidity, mortality, and lifestyle. Annu Rev Public Health. 1984;5:433–458. doi: 10.1146/annurev.pu.05.050184.002245. [DOI] [PubMed] [Google Scholar]

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