The DOI matches its Crossref record, with a small difference in title or year; 67 of the 67 references it cites were found in a registry or an index.
Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men
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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“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
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“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]
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“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]
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“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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“Age, 11,14-17 body mass index (BMI), 12 fasting blood glucose, 1,35 triglycerides, 36 alcohol consumption 13,14 and estradiol levels, 13 which have all been reported to be associated with alteration in hormone levels, were chosen as potential confounding factors in this study.”
From Cigarette smoking has a positive and independent effect on testosterone levels (2013) · cites this paper as [15]
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In the citing paper
“However, it is not possible to be certain that the five patients who failed the GST but passed the SST have intact corticotrophic function because of well-reported falsepass results with the latter test (45)(46)(47)(48).”
From Anterior Pituitary Dysfunction in Survivors of Traumatic Brain Injury (2004) · cites this paper as [47]
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“One study comparing 325 men >age 40 years with self-reported “very good” or “excellent” health demonstrated no significant differences in T levels based on age.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [41]
In the citing paper
“The biologically active forms of T (free T and albumin–bound T) decrease at a greater rate than SHBG-bound or total T during aging,37 likely because of the age-associated increase in SHBG.28, 38, 39”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [28]
In the citing paper
“The anabolic effect of T is reduced during aging due to a gradual and consistent decline in circulating T that begins around the third to fourth decade in men,28, 29 also known as andropause.”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [28]
In the citing paper
“Approximately 40-50% of men over the over the age of 80 have T levels below that of normal healthy young individuals.28, 30”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [28]
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“T consistently declines during this age range.28, 29”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [28]
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Metadata
- 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
- 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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