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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 2 589-598
Copyright © 2002 by The Endocrine Society

Endocrine Care

Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results from the Massachusetts Male Aging Study

Henry A. Feldman, Christopher Longcope, Carol A. Derby, Catherine B. Johannes, Andre B. Araujo, Andrea D. Coviello, William J. Bremner and John B. McKinlay

New England Research Institutes (H.A.F., C.A.D., C.B.J., A.B.A., J.B.M.), Watertown, Massachusetts 02472; University of Massachusetts Medical School (C.L.), Worcester, Massachusetts 01655; and University of Washington Medical School (A.D.C., W.J.B.), Seattle, Washington 98195

Address all correspondence and requests for reprints to: John B. McKinlay, Ph.D., New England Research Institutes, 9 Galen Street, Watertown, Massachusetts 02472. E-mail: johnm{at}neri.org

Abstract

We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40–70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987–1989, 1,156 were followed up 7–10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up.

Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, similarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2–3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally.

Apparent good health, defined as absence of chronic illness, prescription medication, obesity, or excessive drinking, added 10–15% to the level of several androgens and attenuated the cross-sectional trends in T and LH but did not otherwise affect longitudinal or cross-sectional trends.

The paradoxical finding that longitudinal age trends were steeper than cross-sectional trends suggests that incident poor health may accelerate the age-related decline in androgen levels.




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Graded Inhibition of Pulsatile Luteinizing Hormone Secretion by a Selective Gonadotropin-Releasing Hormone (GnRH)-Receptor Antagonist in Healthy Men: Evidence That Age Attenuates Hypothalamic GnRH Outflow
J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2768 - 2774.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. H. McDermott and C. H. Walsh
Hypogonadism in Hereditary Hemochromatosis
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2451 - 2455.
[Abstract] [Full Text] [PDF]

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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
S. J. Fonda, R. Bertrand, A. O'Donnell, C. Longcope, and J. B. McKinlay
Age, Hormones, and Cognitive Functioning Among Middle-Aged and Elderly Men: Cross-Sectional Evidence From the Massachusetts Male Aging Study
J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2005; 60(3): 385 - 390.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. T. Page, J. K. Amory, F. D. Bowman, B. D. Anawalt, A. M. Matsumoto, W. J. Bremner, and J. L. Tenover
Exogenous Testosterone (T) Alone or with Finasteride Increases Physical Performance, Grip Strength, and Lean Body Mass in Older Men with Low Serum T
J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1502 - 1510.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Bhasin, L. Woodhouse, R. Casaburi, A. B. Singh, R. P. Mac, M. Lee, K. E. Yarasheski, I. Sinha-Hikim, C. Dzekov, J. Dzekov, et al.
Older Men Are as Responsive as Young Men to the Anabolic Effects of Graded Doses of Testosterone on the Skeletal Muscle
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 678 - 688.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
P. Y. Liu, S. M. Pincus, D. M. Keenan, F. Roelfsema, and J. D. Veldhuis
Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R440 - R446.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. I. McLachlan and C. A. Allan
Defining the Prevalence and Incidence of Androgen Deficiency in Aging Men: Where Are the Goal Posts?
J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5916 - 5919.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Dhindsa, S. Prabhakar, M. Sethi, A. Bandyopadhyay, A. Chaudhuri, and P. Dandona
Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5462 - 5468.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. Y. Liu, R. S. Swerdloff, and J. D. Veldhuis
The Rationale, Efficacy and Safety of Androgen Therapy in Older Men: Future Research and Current Practice Recommendations
J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4789 - 4796.
[Abstract] [Full Text] [PDF]

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 Arch Gen PsychiatryHome page
P. J. Schmidt, K. L. Berlin, M. A. Danaceau, A. Neeren, N. A. Haq, C. A. Roca, and D. R. Rubinow
The Effects of Pharmacologically Induced Hypogonadism on Mood in Healthy Men
Arch Gen Psychiatry, October 1, 2004; 61(10): 997 - 1004.
[Abstract] [Full Text] [PDF]

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 Hum Reprod UpdateHome page
E. Nieschlag, H.M. Behre, P. Bouchard, J.J. Corrales, T.H. Jones, G.K. Stalla, S.M. Webb, and F.C.W. Wu
Testosterone replacement therapy: current trends and future directions
Hum. Reprod. Update, September 1, 2004; 10(5): 409 - 419.
[Abstract] [Full Text] [PDF]

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 Hum ReprodHome page
K.K. Ng, R. Donat, L. Chan, A. Lalak, I. Di Pierro, and D.J. Handelsman
Sperm output of older men
Hum. Reprod., August 1, 2004; 19(8): 1811 - 1815.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
D. M. de Kretser
Is Spermatogenic Damage Associated with Leydig Cell Dysfunction?
J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3158 - 3160.
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 J. Clin. Endocrinol. Metab.Home page
C. Meier, P. Y. Liu, L. P. Ly, J. de Winter-Modzelewski, M. Jimenez, D. J. Handelsman, and M. J. Seibel
Recombinant Human Chorionic Gonadotropin But Not Dihydrotestosterone Alone Stimulates Osteoblastic Collagen Synthesis in Older Men with Partial Age-Related Androgen Deficiency
J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 3033 - 3041.
[Abstract] [Full Text] [PDF]

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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
S. Asthana, S. Bhasin, R. N. Butler, H. Fillit, J. Finkelstein, S. M. Harman, L. Holstein, S. G. Korenman, A. M. Matsumoto, J. E. Morley, et al.
Masculine Vitality: Pros and Cons of Testosterone in Treating the Andropause
J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2004; 59(5): M461 - M465.
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 J. Clin. Endocrinol. Metab.Home page
A. Hestiantoro and D. F. Swaab
Changes in Estrogen Receptor-{alpha} and -{beta} in the Infundibular Nucleus of the Human Hypothalamus Are Related to the Occurrence of Alzheimer's Disease Neuropathology
J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1912 - 1925.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
B. Z. Leder, J. L. Rohrer, S. D. Rubin, J. Gallo, and C. Longcope
Effects of Aromatase Inhibition in Elderly Men with Low or Borderline-Low Serum Testosterone Levels
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1174 - 1180.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. K. Amory, N. B. Watts, K. A. Easley, P. R. Sutton, B. D. Anawalt, A. M. Matsumoto, W. J. Bremner, and J. L. Tenover
Exogenous Testosterone or Testosterone with Finasteride Increases Bone Mineral Density in Older Men with Low Serum Testosterone
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 503 - 510.
[Abstract] [Full Text] [PDF]

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 NeurologyHome page
V. W. Henderson and E. Hogervorst
Testosterone and Alzheimer disease: Is it men's turn now?
Neurology, January 27, 2004; 62(2): 170 - 171.
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 J. Clin. Endocrinol. Metab.Home page
P. Szulc, B. Claustrat, F. Marchand, and P. D. Delmas
Increased Risk of Falls and Increased Bone Resorption in Elderly Men with Partial Androgen Deficiency: The MINOS Study
J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5240 - 5247.
[Abstract] [Full Text] [PDF]

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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
S. Bhasin
Testosterone Supplementation for Aging-Associated Sarcopenia
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2003; 58(11): M1002 - 1008.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Luboshitzky, Z. Shen-Orr, and P. Herer
Middle-Aged Men Secrete Less Testosterone at Night Than Young Healthy Men
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3160 - 3166.
[Abstract] [Full Text] [PDF]

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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
J. E. Morley
The Need for a Men's Health Initiative
J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2003; 58(7): M614 - 617.
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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
D. L. Waters, C. L. Yau, G. D. Montoya, and R. N. Baumgartner
Serum Sex Hormones, IGF-1, and IGFBP3 Exert a Sexually Dimorphic Effect on Lean Body Mass in Aging
J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2003; 58(7): M648 - 652.
[Abstract] [Full Text] [PDF]

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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
J. E. Morley
Anorexia and Weight Loss in Older Persons
J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2003; 58(2): M131 - 137.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. Colao, C. Di Somma, S. Spiezia, M. Filippella, R. Pivonello, and G. Lombardi
Effect of Growth Hormone (GH) and/or Testosterone Replacement on the Prostate in GH-Deficient Adult Patients
J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 88 - 94.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Luboshitzky, A. Aviv, A. Hefetz, P. Herer, Z. Shen-Orr, L. Lavie, and P. Lavie
Decreased Pituitary-Gonadal Secretion in Men with Obstructive Sleep Apnea
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3394 - 3398.
[Abstract] [Full Text] [PDF]


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