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Cited by 55Hormonal and reproductive studiesHypothalamic control of reproductive hormonesSperm and Testicular Function

Aging and androgens: Physiology and clinical implications

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Anawalt, Bradley D., Matsumoto, Alvin M.·2022·Reviews in Endocrine and Metabolic Disorders
DOI 10.1007/s11154-022-09765-2PMC PMC10370404
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Abstract

In men > ~35 years, aging is associated with perturbations in the hypothalamus-pituitary-testicular axis and declining serum testosterone concentrations. The major changes are decreased gonadotropin-releasing hormone (GnRH) outflow and decreased Leydig cell responsivity to stimulation by luteinizing hormone (LH). These physiologic changes increase the prevalence of biochemical secondary hypogonadism-a low serum testosterone concentration without an elevated serum LH concentration. Obesity, medications such as opioids or corticosteroids, and systemic disease further reduce GnRH and LH secretion and might result in biochemical or clinical secondary hypogonadism. Biochemical secondary hypogonadism related to aging often remits with weight reduction and avoidance or treatment of other factors that suppress GnRH and LH secretion. Starting at age ~65-70, progressive Leydig cell dysfunction increases the prevalence of biochemical primary hypogonadism-a low serum testosterone concentration with an elevated serum LH concentration. Unlike biochemical secondary hypogonadism in older men, biochemical primary hypogonadism is generally irreversible. The evaluation of low serum testosterone concentrations in older men requires a careful assessment for symptoms, signs and causes of male hypogonadism. In older men with a body mass index (BMI) ≥ 30, biochemical secondary hypogonadism and without an identifiable cause of hypothalamus or pituitary pathology, weight reduction and improvement of overall health might reverse biochemical hypogonadism. For older men with biochemical primary hypogonadism, testosterone replacement therapy might be beneficial. Because aging is associated with decreased metabolism of testosterone and increased tissue-specific androgen sensitivity, lower dosages of testosterone replacement therapy are often effective and safer in older men.

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  • Declines in testosterone per year of age are 2-3-fold greater with longitudinal compared with cross-sectional analysis of the same cohort.

    “This is because declines in testosterone per year of age is 2–threefold greater with longitudinal compared with cross-sectional analysis of the same cohort [35, 36].”

    From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [36]

    The section on epidemiology of serum testosterone concentrations associated with aging in men (page not available) says that the observed annual decline is smaller in cross-sectional than in longitudinal studies. It does not establish that the longitudinal decline is two- to threefold greater, or that the comparison comes from analyses of the same cohort. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Anawalt, B. D., & Matsumoto, A. M.
Affiliations
University of Washington (US)
Corresponding author
Anawalt, Bradley D.
ORCID
Venue
Reviews in Endocrine and Metabolic Disorders
Publisher
Springer Science and Business Media LLC
Published
2022-12
Volume
23
Issue
6
Pages
1123-1137
ISSN
  • 1389-9155 (ISSN-L)
  • 1573-2606
DOI
10.1007/s11154-022-09765-2
PMC
PMC10370404
OpenAlex
W4310576960
Cited by
55
References
19
Citations by year
2026: 18 · 2025: 18 · 2024: 12 · 2023: 6 · 2022: 1
FWCI
42.41
Type
book chapter
Language
en
Open access
Licence
Locations
  • Reviews in Endocrine and Metabolic Disorders (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL134653)
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 › Reproductive Medicine › Sperm and Testicular Function
Keywords
male hypogonadism, aging, testosterone, androgens, hypothalamic-pituitary-testicular axis, gonadotropin-releasing hormone, luteinizing hormone, Leydig cell dysfunction, obesity, testosterone replacement therapy, older men, weight loss
MeSH terms
Aged, Aging, Androgens, Humans, Hypogonadism, Gonadotropin-Releasing Hormone, Male, Testosterone

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