Age-related changes in male gonadal function. Implications for therapy

Drugs and Aging

Volumn 11, Issue 1, 1997, Pages 45-60

  Maas, Diana ^a,b   Jochen, Albert ^a   Lalande, Beth ^a  

^a CLEMENT J ZABLOCKI VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; SEX HORMONE BINDING GLOBULIN; TESTOSTERONE;

AGING; ANDROGEN SYNTHESIS; ANDROGEN THERAPY; BONE DENSITY; DRUG DELIVERY SYSTEM; ENVIRONMENTAL FACTOR; ERYTHROCYTOSIS; GONAD FUNCTION; HORMONE SUBSTITUTION; HUMAN; HYPOPHYSIS GONAD SYSTEM; INTRAMUSCULAR DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; MALE; MALE GENITAL SYSTEM FUNCTION; METABOLISM; MUSCLE STRENGTH; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATE HYPERTROPHY; REVIEW; RISK; SLEEP APNEA SYNDROME; TESTIS; TESTOSTERONE SYNTHESIS; TRANSDERMAL DRUG ADMINISTRATION; WELLBEING;

EID: 0030751699     PISSN: 1170229X     EISSN: None     Source Type: Journal    
DOI: 10.2165/00002512-199711010-00005     Document Type: Review

References (128)

1. Hollander N, Hollander VP. The microdetermination of testosterone in human spermatic vein blood. J Clin Endocrinol Metab 1958 Sep; 18: 966-71
2. Coppage Jr WS, Cooner AB. Testosterone in human plasma. N Engl J Med 1965; 273: 902-7
3. Gandy HM, Peterson RE. Measurement of testosterone and 17-ketosteroids in plasma by the double isotope dilution derivative technique. J Clin Endocrinol Metab 1968 Jul; 28: 949-77
4. Kent JR, Acone AB. Plasma testosterone levels and aging in males. Int Congress Series 1966; 101: 31-5
5. Vermeulen A, Rubens R, Verdonck L. Testosterone secretion and metabolism in male senescence. J Clin Endocrinol Metab 1972; 34: 730-5
6. Nieschlag E, Kley KH, Wiegelmann W. Age dependence of the endocrine testicular function in adult men [abstract]. Acta Endocrinol Suppl 1973; 177: 122
7. Pirke KM, Doerr P. Age related changes and interrelationships between plasma testosterone, oestradiol and testosterone-binding globulin in normal adult males. Acta Endocrinol (Copenh) 1973; 74: 792-800
8. Rubens R, Dhont M, Vermeulen A. Further studies on Leydig cell function in old age. J Clin Endocrinol Metab 1974; 39: 40-5
9. Stearns EL, MacDonnell JA, Kaufman BJ, et al. Declining testicular function with age: hormonal and clinical correlates. Am J Med 1974; 57: 761-6
10. Harman SM, Tsitouras PD. Reproductive hormones in aging men: I. Measurement of sex steroids, basal luteinizing hormone, and Leydig cell response to human chorionic gonadotropin. J Clin Endocrinol Metab 1980; 51: 35-40
11. Sparrow D, Bosse R, Rowe JW. The influence of age, alcohol consumption, and body build on gonadal function in men. J Clin Endocrinol Metab 1980; 51: 508-12
12. Murono EP, Nankin HR, Lin T, et al. The aging Leydig cell: V. Diurnal rhythms in aged men. Acta Endocrinol 1982; 99: 619-23
13. Nieschlag E, Lammers U, Freischem CW, et al. Reproductive functions in young fathers and grandfathers. J Clin Endocrinol Metab 1982; 55: 676-81
14. Nankin HR, Calkins JH. Decreased bioavailable testosterone in aging normal and impotent men. J Clin Endocrinol Metab 1986; 63: 1418-24
15. Urban RJ, Veldhuis JD, Blizzard RM, et al. Attenuated release of biologically active luteinizing hormone in healthy aging men. J Clin Invest 1988; 81: 1020-9
16. Diaz Sanchez V, Altamirano A, Peret Palacios G. Changes in the pituitary-testicular axis function with age in normal males. Arch Invest Med (Mex) 1988; 19 (3): 309-17
17. Tenover JS, Bremner WJ. The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men. J Androl 1991; 12 (4): 258-63
18. Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Human Biol 1981; 53: 499-511
19. Winters SJ, Troen P. Episodic luteinizing hormone (LH) secretion and the response of LH and follicle-stimulating hormone to LH-releasing hormone in aged men: evidence for coexistent primary testicular insufficiency and an impairment in gonadotropin secretion. J Clin Endocrinol Metab 1982; 55: 560-5
20. Zumoff B, Strain GW, Kream J, et al. Age variation of the 24-hour mean plasma concentrations of androgens, estrogens, and gonadotropins in normal adult men. J Clin Endocrinol Metab 1982; 54: 534-8
21. Davidson JM, Chen JJ, Crapo L, et al. Hormonal changes and sexual function in aging men. J Clin Endocrinol Metab 1983; 57: 71-6
22. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab 1983; 56: 1278-81
23. Winters SJ, Sherins RJ, Troen P. The gonadotropin-suppressive activity of androgen is increased in elderly men. Metab Clin Exper 1984; 33: 1052-9
24. Tsitouras PD, Hagen TC. Testosterone, LH, FSH, prolactin and sperm in aging healthy men. In: Abstracts of the 7th International Congress of Endrocrinology. Excerpta Medica, 1984: 1236
25. Deslypere JP, Vermeulen A. Leydig cell function in normal men: effect of age, lifestyle, residence, diet and activity. J Clin Endocrinol Metab 1984; 59: 955-62
26. Warner RA, Dufau ML, Santen RJ. Effects of aging and illness on the pituitary testicular axis in men: qualitative as well as quantitative changes in luteinizing hormone. J Clin Endocrinol Metab 1985; 60: 263-8
27. Moroz EV, Verkhratsky NS. Hypophyseal-gonadal system during male aging. Arch Gerontol Geriatr 1985; 4: 13-9
28. Tenover JS, Matsumoto AM, Plymate SR, et al. The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate. J Clin Endocrinol Metab 1987; 65: 1118-25
29. Deslypere JP, Kaufman JM, Vermeulen T, et al. Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men. J Clin Endocrinol Metab 1987; 64: 68-73
30. Plymate SR, Tenover JS, Bremner WJ. Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men. J Androl 1989; 10 (5): 366-71
31. Nahoul K, Roger M. Age-related decline of plasma bioavailable testosterone in adult men. J Steroid Biochem 1990; 35: 293-9
32. Korenman SG, Morley JE, Mooradian AD, et al. Secondary hypogonadism in older men: its relation to impotence. J Clin Endocrinol Metab 1990; 71: 963-9
33. Gray A, Feldman HA, McKinlay JB, et al. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991; 73: 1016-25
34. Veldhuis JD, Urban RJ, Lizarralde G, et al. Attenuation of luteinizing hormone secretory burst amplitude as a proximate basis for the hypoandrogenisin of healthy aging in men. J Clin Endocrinol Metab 1992; 75: 707-13
35. Ravaglia G, Forti P, Maioli F, et al. Hormonal changes in male subjects over ninety. Boll Soc Ital Biol Sper 1995; 71 (5-6): 133-9
36. Mitchell R, Hollis S, Rothwell C, et al. Age related changes in the pituitary-testicular axis in normal men: lower serum testosterone results from decreased bioactive LH drive. Clin Endocrinol 1995; 42: 501-7
37. Erfurth EMT, Hagmar LE. Decreased serum testosterone and free triiodothyronine levels in healthy middle-aged men indicate an age effect at the pituitary level. Eur J Endocrinol 1995; 132: 663-7
38. Yamaguchi M-A, Mizunuma H, Miyamoto K, et al. Immunoreactive inhibin concentrations in adult men: presence of a circadian rhythm. J Clin Endocrinol Metab 1991; 72: 554-9
39. Manni A, Pardridge WM, Cefalu W, et al. Bioavailability of albumin-bound testosterone. J Clin Endocrinol Metab 1985; 61: 705-10
40. Cumming DC, Wall SR. Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism. J Clin Endocrinol Metab 1985; 62: 873-6
41. Bartsch W. Interrelationships between sex hormone-binding globulin and testosterone, 5a-dihydrotestosterone and oestradiol-17β in blood of normal men. Maturitas 1980; 2 (2): 109-18
42. Vermeulen A. The male climacterium. Ann Med 1993; 25: 531-4
43. Vermeulen A. Androgens in the aging male. J Clin Endocrinol Metab 1991; 71 (2): 221-4
44. Lewis JG, Ghanadian R, Chisolm GD. Serum 5a-dihydrolestosterone and testosterone changes with age in man. Acta Endocrinol 1976; 82: 444-8
45. Waldstreicher J, Gormley G, Cook T, et al. Absence of age-associated decline in testosterone (T) and dihydrotestosterone (DHT) in men with benign prostatic hyperplasia [abstract 380]. Proceedings of the 75th Annual Meeting of the Endocrine Society; 1993 Jun 9-12: Las Vegas. Bethesda (MD): Endocrine Society Press, 1993
46. Bartsch W, Becker H, Pinkenburg FA, et al. Hormone blood levels and their inter-relationships in normal men and men with benign prostatic hyperplasia. Acta Endocrinol 1979; 90: 727-36
47. Barrett-Connor E, Khaw K-T, Yen SSC. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med 1986; 315: 1519-24
48. Smith MR, Rudd BT, Shirley A, et al. A radioimmunoassay for the estimation of serum dehydroepiandrosterone sulphate in normal and pathological sera. Clin Chim Acta 1975; 65: 5-13
49. Yamaji T, Ibayashi H. Plasma dehydroepiandrosterone sulfate in normal and pathological conditions. J Clin Endocrinol Metab 1969; 29: 273-8
50. Vermeulen A. Adrenal androgens and aging. In: Genazzani AR, Thijssen JHH, Sitteri PK, editors. Adrenal androgens. New York: Raven Press, 1980: 207-17
51. Orentreich N, Brind JL, Rizer RL, et al. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 1984; 59: 551-5
52. Gray A, Berlin JA, McKinlay JB, et al. An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis. J Clin Endocrinol Metab 1991; 44: 671-84
53. Vermeulen A, Kaufman JM. Ageing of the hypothalamo-pituitary-testicular axis in men. Horm Res 1995; 43: 25-8
54. Harman SM, Blankman MR. Male menopause, myth or menace? Endocrinologist 1994; 4 (3): 212-7
55. Blackman MR, Weintraub BD, Rosen SW, et al. Comparison of the effects of lung cancer, benign lung disease and normal ageing on pituitary-gonadal function in men. J Clin Endocrinol Metab 1988; 66: 88-95
56. Cameron JL, Weltzin TE, McConaha C, et al. Luteinizing hormone secretion in men after forty-eight hours of fasting. J Clin Endocrinol Metab 1991; 72: 35-41
57. Kley HK, Nieschlag E, Bidlingmaier F, et al. Possible age-dependent influence of estrogens on the binding of testosterone in plasma of adult men. J Clin Endocrinol Metab 1974; 33: 759-67
58. Vermeulen A, Stoica T, Verdonck L. The apparent free testosterone concentration, an index of androgenicity. J Clin Endocrinol Metab 1971; 33: 759-67
59. Longcope C, Goldfield SRW, Brambilla DJ, et al. Androgens, estrogens, and sex hormone-binding globulin in middle-aged men. J Clin Endocrinol Metab 1990; 71 (6): 1442-6
60. Glass AR, Swerdloff RS, Bray GA, et al. Low serum testosterone and sex-hormone-binding globulin in massively obese men. J Clin Endocrinol Metab 1977; 45: 1211-9
61. Semmens JB, Rouse IL, Beilin LJ, et al. Relationships between age, body weight, physical fitness and sex-hormone-binding globulin capacity. Clin Chim Acta 1993; 133: 295-300
62. Skoldefors H, Carlstrom K, Eneroth P. Influence of aging upon the serum hormone levels in the male. Int J Androl 1978; 1: 308-16
63. Blackman MR. Aging. In: DeGroot LJ, editor. Endocrinology. Vol. 3. Philadelphia: W.B. Saunders Co., 1989: 2348-66
64. Villareal DT, Morley JE. Trophic factors in aging: should older people receive hormonal replacement therapy? Drugs Aging 1994; 4 (6): 492-509
65. Neaves WB, Johnson L, Porter JC, et al. Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men. J Clin Endocrinol Metab 1984; 59: 756-63
66. Bishop MWH. Aging and reproduction in the male. J Reprod Fert 1970; 21 Suppl. 12: 65-87
67. Christiansen P. Urinary follicle stimulating hormone and luteinizing hormone in normal adult men. Acta Endocrinol 1972; 71: 1-6
68. MacNaughton JA, Bangah ML, McCloud PI, et al. Inhibin and age in men. Clin Endocrinol 1991; 35: 341-6
69. Tenover JS, Bremner WJ. Circadian rhythm of serum immunoreactive inhibin in young and elderly men. J Gerontol 1991; 46: 181-4
70. Johnson L, Petty CS, Neaves WB. Age related variations in seminiferous tubules in men: a stereologic evaluation. J Androl 1986; 7: 316-22
71. Marrama P, Montanini V, Celani MF, et al. Decrease in luteinizing hormone biological activity/immunoreactivity ratio in elderly men. Maturitas 1984; 5: 223-31
72. Sniffen RC. The testes: I. The normal testes. Arch Pathol 1950; 50: 259-84
73. Harbitz TB. Morphometric studies of Leydig cells in elderly men, with special reference to the histology of the prostate. Acta Pathol Microbiol Scand 1973; 891: 301-13
74. Longscope C. The effect of human chorionic gonadotropin on plasma levels in young and old men. Steroids 1973; 21: 583-90
75. Nankin HR, Lin T, Murono EP, et al. The aging Leydig cell: III. Gonadotropin stimulation in men. J Androl 1981; 2: 181-4
76. Billington CJ, Shafer RB, Morley JE. Effects of opioid blockage with halmetene in older impotent men. Life Sci 1990; 47: 795-805
77. Vermeulen A, Deslypere JP, Kaufman JM. Influence of anti-opioids on luteinizing hormone pulsatility in aging men. J Clin Endocrinol Metab 1989; 68: 68-72
78. Spark RF. Neuroendocrinology and impotence. Ann Intern Med 1983; 98: 103-5
79. Kaiser FE, Viosca SP, Morley JE, et al. Impotence and aging: clinical and hormonal factors. J Am Geriatr Soc 1988; 36: 511-9
80. Morley JE. Endocrine factors in geriatric sexuality. Clin Geriatr Med 1991; 7: 85-93
81. Kaufman JM, Giri M, Deslypere JP, et al. Influence of age on the responsiveness of gonadotrophs to luteinizing hormone-releasing hormone in males. J Clin Endocrinol Metab 1991; 72: 221-4
82. Snyder PJ, Reitano JF, Utiger RD. Serum LH and FSH responses to synthetic gonadotropin-releasing hormone in normal men. J Clin Endocrinol Metab 1975; 41: 938-45
83. Harman SM, Tsotpiras D, Costa PT, et al. Reproductive hormones in aging men: basal pituitary gonadotropins and gonadotropin responses to luteinizing hormone-releasing hormone. J Clin Endocrinol Metab 1982; 54: 547-51
84. Pontiroli AE, Ruga S, Maffi P, et al. Pituitary reserve after repeated administrations of releasing hormones in young and in elderly men: reproducibility on different days. J Endocrinol Invest 1992; 15: 559-66
85. Marini GG, Traverso L, Cavagnaro P, et al. Effect of pulsatile luteinizing hormone-releasing hormone administration on pituitary-gonadal function in elderly man. J Endocrinol Invest 1990; 13: 127-32
86. Guay AT, Bansal S, Hodge MB. Possible hypothalamic impotence: male counterpart to hypothalamic amenorrhea? Urology 1991; 38 (14): 317-22
87. Vermeulen A, Kaufman JM, Deslypere JP, et al. Attenuated LH pulse amplitude but normal LH pulse frequency and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab 1993; 76: 1140-6
88. Muta K, Kato K, Akamine Y, et al. Age-related changes in the feedback regulation of gonadotropin secretion by sex steroids in men. Acta Endocrinol (Copenh) 1981; 96: 154-62
89. Deslypere JP, Vermeulen A. Aging and tissue androgens. J Clin Endocrinol Metab 1981; 53: 530-4
90. Aiman J, Griffin JE, Gazak JM, et al. Androgen insensitivity as a cause of infertility in otherwise normal men. N Engl J Med 1979; 300: 223-7
91. Baran DT, Bergfeld MA, Teitelbaum SL, et al. Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male. Calcif Tiss Res 1978; 26: 103-6
92. Brodsky IG, Balagopal P, Sreekumaran Nair K. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men - a Clinical Research Center study. J Clin Endocrinol Metab 1996; 81: 3469-75
93. Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Metab Endocrinol 1992; 75: 1092-8
94. Morley JE, Perry NM, Kaiser FE, et al. Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc 1993; 41: 149-52
95. Burris AS, Banks SM, Carter CS, et al. A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men. J Androl 1992; 13: 297-304
96. Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men - a Clinical Research Center study. J Clin Endocrinol Metab 1996; 81: 3578-83
97. Abbasi AA, Drinka PJ, Mattson DE, et al. Low circulating levels of insulin-like growth factors and testosterone in chronically institutionalized elderly men. J Am Geriatr Soc 1993; 41: 975-82
98. Häkkinen K, Pakarinen A. Serum hormones and strength development during strength training in middle-aged and elderly males and females. Acta Physiol Scand 1994; 150: 211-9
99. Urban RJ, Bodenburg YH, Gilkison C, et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 1995; 269: E820-6
100. Simon D, Preziosi P, Barrett-Connor E, et al. Interrelation between plasma testosterone and plasma insulin in healthy adult men: the Telecom Study. Diabetologia 1992; 35: 173-7
101. Deutscher S, Bates MW, Caines MJ, et al. Relationships between serum testosterone, fasting insulin and lipoprotein levels among elderly men. Atherosclerosis 1989; 75: 13-22
102. Crook D, Sidhu M, Seed M, et al. Lipoprotein Lp(a) levels are reduced by danazol, an anabolic steroid. Atherosclerosis 1992; 92: 41-7
103. Caron P, Bennet A, Camare R, et al. Plasminogen activator inhibitor in plasma is related to testosterone in men. Metabolism 1989; 38: 1010-5
104. Tsitouras PD, Martin CE, Harman SM. Relationship of serum testosterone to sexual activity in healthy elderly men. J Gerontol 1982; 37: 288-93
105. Buena F, Swerdloff RS, Steiner BS, et al. Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal range. Fertil Steril 1993; 59: 1118-23
106. Snyder PJ, Lawrence DA. Treatment of male hypogonadism with testosterone enanthate. J Clin Endocrinol Metab 1980; 51: 1335-9
107. Ahmed SR, Boucher AE, Manni A, et al. Transdermal testosterone therapy in the treatment of male hypogonadism. J Clin Endocrinol Metab 1988; 66: 646-51
108. Findlay JC, Place V, Snyder PJ. Treatment of primary hypogonadism in men by the transdermal administration of testosterone. J Clin Endocrinol Metab 1989; 68: 369-73
109. Meikle AW, Mazer NA, Moellmer JF, et al. Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiologic concentrations of testosterone and its metabolites in hypogonadal men. J Clin Endocrinol Metab 1992; 74: 623-8
110. Salahian B, Wang C, Alexander G, et al. Pharmacokinetics, bioefficacy and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate. J Clin Endocrinol Metab 1995; 80: 3567-75
111. Wang C, Eyre DR, Clark R, et al. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men - a Clinical Research Center study. J Clin Endocrinol Metab 1996; 81: 3654-62
112. Weber JP, Oesterling JE, Peters CR, et al. The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia. J Urol 1989; 141: 987-92
113. Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf) 1994; 40: 341-9
114. Gagnon DR, Zhang T-J, Brand FN, et al. Hematocrit and the risk of cardiovascular disease. The Framingham Study: a 34-year follow-up. Am Heart J 1994; 127: 674-82
115. Matsumoto AM, Sandblom RE, Schoene RB, et al. Testosterone replacement in hypogonadal men: effects on obstructive sleep apnea, respiratory drives and sleep. Clin Endocrinol 1985; 22: 713-21
116. Drinka PJ, Jochen AL, Ciusinier M, et al. Polycythemia as a complication of testosterone replacement therapy in nursing home men with low testosterone levels. J Am Geriatr Soc 1995; 43: 899-901
117. Shahidi NT. Androgens and erythropoiesis. N Engl J Med 1973; 289: 72-80
118. Sandblom RE, Matsumoto AM, Schoene RB, et al. Obstructive sleep apnea syndrome induced by testosterone administration. N Engl J Med 1983; 308: 508-10
119. Schneider BK, Picket CK, Zwillich CW, et al. Influence of testosterone on breathing during sleep. J Appl Physiol 1986; 61: 618-23
120. McNutt RA, Ferenchik GS, Kirlin PL, et al. Acute myocardial infarction in a 22-year-old world class weight lifter using anabolic steroids. Am J Cardiol 1988; 62: 164-8
121. Webb OL, Laskarzewski PM, Glueck CJ. Severe depression of high-density lipoprotein cholesterol levels in weight lifters and body builders by self-administered exogenous testosterone and anabolic-androgenic steroids. Metabolism 1984; 33: 971-5
122. Thompson PD, Cullinane EM, Sady SP, et al. Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. JAMA 1989; 261: 1165-8
123. Sorva R, Kuusi T, Taskinen M-R, et al. Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal males. Atherosclerosis 1988; 69: 191-7
124. Gutai J, Laporte R, Kuller L, et al. Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions. Am J Cardiol 1981; 48: 897-902
125. Godsland IF, Wynn V, Crook D, et al. Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions. Am Heart J 1987; 114: 1467-503
126. Barrett-Connor E, Khaw K-T. Endogenous sex hormones and cardiovascular disease in men: a prospective population-based study. Circulation 1988; 78: 539-45
127. Haffner SM, Laakso M, Miettinen H, et al. Low levels of sex-hormone-binding globulin are associated with smaller, denser low density lipoprotein in normoglycemic men. J Clin Endocrinol Metab 1996; 81: 3697-701
128. 2 receptor density and aggregation responses. Circulation 1995; 91: 2742-7