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Trans Am Clin Climatol Assoc. 1990; 101: 168–189.
PMCID: PMC2376508
PMID: 2486441

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

W. R. Hazzard and D. Applebaum-Bowden
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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.
  • Hazzard WR. Biological basis of the sex differential in longevity. J Am Geriatr Soc. 1986 Jun;34(6):455–471. [PubMed]
  • Fries JF. Aging, natural death, and the compression of morbidity. N Engl J Med. 1980 Jul 17;303(3):130–135. [PubMed]
  • Fries JF, Green LW, Levine S. Health promotion and the compression of morbidity. Lancet. 1989 Mar 4;1(8636):481–483. [PubMed]
  • ROCKSTEIN M, LIEBERMAN HM. A life table for the common house fly, Musca domestica. Gerontologia. 1959;3:23–36. [PubMed]
  • McMillen MM. Differential mortality by sex in fetal and neonatal deaths. Science. 1979 Apr 6;204(4388):89–91. [PubMed]
  • Wingard DL. The sex differential in morbidity, mortality, and lifestyle. Annu Rev Public Health. 1984;5:433–458. [PubMed]
  • Holden C. Can smoking explain ultimate gender gap? Science. 1983 Sep 9;221(4615):1034–1034. [PubMed]
  • Knopp RH, Walden CE, Wahl PW, Hoover JJ, Warnick GR, Albers JJ, Ogilvie JT, Hazzard WR. 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. [PubMed]
  • Bradley DD, Wingerd J, Petitti DB, Krauss RM, 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. [PubMed]
  • RUSS EM, EDER HA, BARR DP. Influence of gonadal hormones on protein-lipid relationships in human plasma. Am J Med. 1955 Jul;19(1):4–24. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Godsland IF, Wynn V, Crook D, Miller NE. Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions. Am Heart J. 1987 Dec;114(6):1467–1503. [PubMed]
  • Matthews KA, Meilahn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N Engl J Med. 1989 Sep 7;321(10):641–646. [PubMed]
  • Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, Tyroler HA, Rifkind BM. 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. [PubMed]
  • Ross RK, Paganini-Hill A, Mack TM, Arthur M, Henderson BE. Menopausal oestrogen therapy and protection from death from ischaemic heart disease. Lancet. 1981 Apr 18;1(8225):858–860. [PubMed]
  • Stampfer MJ, Willett WC, Colditz GA, Rosner B, Speizer FE, Hennekens CH. A prospective study of postmenopausal estrogen therapy and coronary heart disease. N Engl J Med. 1985 Oct 24;313(17):1044–1049. [PubMed]
  • Wilson PW, Garrison RJ, Castelli WP. 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. [PubMed]
  • Miller NE, Thelle DS, Forde OH, Mjos OD. The Tromsø heart-study. High-density lipoprotein and coronary heart-disease: a prospective case-control study. Lancet. 1977 May 7;1(8019):965–968. [PubMed]
  • Musliner TA, Herbert PN, Kingston MJ. Lipoprotein substrates of lipoprotein lipase and hepatic triacylglycerol lipase from human post-heparin plasma. Biochim Biophys Acta. 1979 Nov 21;575(2):277–288. [PubMed]
  • Shirai K, Barnhart RL, Jackson RL. 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. [PubMed]
  • Cheung MC, Albers JJ, Wahl PW, Hazzard WR. High density lipoproteins during hypolipidemic therapy. A comparative study of four drugs. Atherosclerosis. 1980 Mar;35(3):215–228. [PubMed]
  • Taggart HM, Applebaum-Bowden D, Haffner S, Warnick GR, Cheung MC, Albers JJ, Chestnut CH, 3rd, Hazzard WR. Reduction in high density lipoproteins by anabolic steroid (stanozolol) therapy for postmenopausal osteoporosis. Metabolism. 1982 Nov;31(11):1147–1152. [PubMed]
  • Haffner SM, Kushwaha RS, Foster DM, Applebaum-Bowden D, Hazzard WR. Studies on the metabolic mechanism of reduced high density lipoproteins during anabolic steroid therapy. Metabolism. 1983 Apr;32(4):413–420. [PubMed]
  • Chesnut CH, 3rd, Ivey JL, Gruber HE, Matthews M, Nelp WB, Sisom K, Baylink DJ. Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action. Metabolism. 1983 Jun;32(6):571–580. [PubMed]
  • Applebaum-Bowden D, Haffner SM, Hazzard WR. 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. [PubMed]
  • Hazzard WR, Haffner SM, Kushwaha RS, Applebaum-Bowden D, Foster DM. 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. [PubMed]
  • Windler EE, Kovanen PT, Chao YS, Brown MS, Havel RJ, Goldstein JL. 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]
  • Ma PT, Yamamoto T, Goldstein JL, Brown MS. 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. [PMC free article] [PubMed]
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