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Cited by 2,760Hormonal and reproductive studiesHypothalamic control of reproductive hormonesMenopause: Health Impacts and Treatments

Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men

Harman, S. Mitchell, Metter, E. Jeffrey, Tobin, Jordan D., Pearson, Jay, Blackman, Marc R.·2001·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.86.2.7219
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Abstract

Many studies have shown cross-sectional (and two small studies, longitudinal) declines in total and/or free testosterone (T) levels, with age, in men. The extent to which decline in T is the result of the aging process per se, as opposed to chronic illness, medication use, and other age-related factors, remains controversial. The frequency with which aging leads to T levels consistent with hypogonadism has also not been defined. These issues bear on the potential use of T replacement in aging men, because aging and hypogonadism have, in common, reduced bone and lean body mass and muscle strength and increased total and abdominal fat. We measured T and sex hormone-binding globulin (SHBG), by RIA, in stored samples from 890 men in the Baltimore Longitudinal Study on Aging. Using a mixed-effects model, we found independent effects of age and date of sampling to reduce T levels. After compensating for date effects, which investigation suggested was artifactual, we observed significant, independent, age-invariant, longitudinal effects of age on both T and free T index (free T index = T/SHBG), with an average change of -0.124 nmol/L.yr and -0.0049 nmol T/nmol SHBG.yr. T, but not free T index, also decreased with increasing body mass index. Use of beta-blocking drugs was associated with higher T and higher free T index levels. Using total T criteria, incidence of hypogonadal T levels increased to about 20% of men over 60, 30% over 70 and 50% over 80 yr of age, and even greater percentages when free T index criteria were employed. Our observations of health factor independent, age-related longitudinal decreases in T and free T, resulting in a high frequency of hypogonadal values, suggest that further investigation of T replacement in aged men, perhaps targeted to those with the lowest serum T concentrations, are justified.

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Crossref · 10.1210/jcem.86.2.7219

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  • Testosterone deficiency is highly prevalent, with rates increasing with age from 4% in men aged 40-49 years to nearly 50% in men over 80 years, and some studies suggest a 17% increase per decade of life.

    “Testosterone deficiency is highly prevalent, with rates increasing with age from 4% in men aged 40–49 years to nearly 50% in men over 80 years of age, with some studies suggesting a 17% increase in testosterone deficiency for every decade of life (2-4).”

    From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [3]

    The Occurrence of hypogonadism section reports that low total-testosterone values rose with age, reaching 49% among men in their 80s, which supports the nearly 50% figure. It describes rates below age 49 only as relatively low; our copy does not give the claimed 4% for men aged 40–49 or a 17% increase in deficiency per decade. The study defines hypogonadism by measured hormone thresholds rather than confirmed clinical deficiency. (LLM, conf=0.88)

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  • Serum testosterone levels decline with age, commencing in men in their mid-30s and decreasing at an average annual rate of 1.6%.

    “We speculate that this phenomenon may be attributed to the gradual decline in serum testosterone levels with age, commencing in men in their mid-30s and decreasing at an average annual rate of 1.6%38–43.”

    From Association between serum cotinine and total testosterone in adult males based on NHANES 2011–2016 (2024) · cites this paper as [41]

    The Discussion reports that serum testosterone declined progressively with age in the men studied, from the third through ninth decades. It does not identify the mid-30s as the onset or report an average decline of 1.6% per year; it gives a total-testosterone decline of 0.110 nmol/L (3.2 ng/dL) per year instead. Page numbers were not available in our copy. (LLM, conf=0.88)

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  • Normal aging is associated with a decrease of testosterone levels by 1% to 2% per year.

    “By comparison, normal aging is associated with a decrease of testosterone levels by 1% to 2% per year.6”

    From Effect of 1 Week of Sleep Restriction on Testosterone Levels in Young Healthy Men (2011) · cites this paper as [6]

    The Discussion reports that total testosterone and the free testosterone index declined with age in 890 generally healthy men, but gives the annual decline in absolute units, not as 1%–2%. Its reported total-testosterone decline of 0.110 nmol/L per year is about 0.6% of the 17.6 nmol/L mean for younger men given in Statistical analysis. The specific 1%–2% annual rate is therefore not established for testosterone levels generally. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Age, cigarette smoking, BMI, alcohol consumption and physical activity have been reported to be probably or possibly associated with hormone levels.

    “Probable and possible associations of several factors, including age, cigarette smoking, body mass index (BMI), alcohol consumption and physical activity with hormone levels have been reported. 11-17”

    From Cigarette smoking has a positive and independent effect on testosterone levels (2013) · cites this paper as [15]

    The Multivariate analysis (page unavailable) reports associations of age, BMI, and alcohol consumption with testosterone or the free testosterone index. The Discussion (page unavailable) notes a smoking association in a previous study, although this study found no significant smoking effect. The copy does not report an association between physical activity and hormone levels. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The reported effects of smoking on testosterone levels in men are controversial, with some evidence suggesting no association and others reporting higher or lower total testosterone levels among smokers compared to nonsmokers.

    “However, the reported effects of smoking on testosterone levels in men are controversial, with some evidence even suggesting no association 15,19-24 and others reporting higher 13,14,25-32 or lower 33,34 levels of TT among smokers compared to nonsmokers.”

    From Cigarette smoking has a positive and independent effect on testosterone levels (2013) · cites this paper as [15]

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Authors
Harman, S. M., Metter, E. J., Tobin, J. D., Pearson, J., & Blackman, M. R.
Affiliations
  • National Institutes of Health (US)
  • Johns Hopkins University (US)
ORCID
Harman, S. Mitchell
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2001-02
Volume
86
Issue
2
Pages
724-731
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.86.2.7219
OpenAlex
W2139893960
Cited by
2,760
References
67
Citations by year
2026: 63 · 2025: 88 · 2024: 78 · 2023: 83 · 2022: 110 · 2021: 112 · 2020: 116 · 2019: 113 · 2018: 107 · 2017: 153 · 2016: 128 · 2015: 129 · 2014: 138 · 2013: 128 · 2012: 133
FWCI
54.02
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
aging, testosterone, free testosterone, hypogonadism, sex hormone-binding globulin, longitudinal decline, healthy older men, body mass index, beta-blockers, testosterone replacement therapy
MeSH terms
Adult, Aging, Humans, Hypogonadism, Longitudinal Studies, Male, Middle Aged, Radioimmunoassay, Regression Analysis, Sex Hormone-Binding Globulin, Social Class, Testosterone, Baltimore, Reproducibility of Results, White People

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