The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men
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ABSTRACT: Serum androgens decline with age in normal men, despite normal or elevated bioactive serum gonadotropins, suggesting that primary testicular dysfunction occurs with aging. The authors further assessed the question of age‐related testicular dysfunction by evaluating whether raising serum gonadotropins above the normal serum range for an extended time in healthy elderly men might result in bringing their gonadal function to a level similar to that found in young adult men. Five elderly (65 to 85 years old) and five young adult men (26 to 33 years old) were given 50 mg of clomiphene citrate (CC) twice a day for 8 weeks to stimulate gonadotropin production. During that time, testosterone (T), non‐sex hormone‐binding globulin bound T, and estradiol increased significantly in both age groups, while serum inhibin increased significantly only in the young adult men. The increases in serum androgens with CC administration were significantly greater in the young adult men than in the elderly men. These hormone changes occurred in the setting of serum gonadotropins that increased significantly in both age groups, although there was a tendency for the elderly men to have a smaller increase in luteinizing hormone. Despite 8 weeks of stimulation of the pituitary‐gonadal axis by CC administration, the elderly men demonstrated significantly diminished testicular responses compared with the young adult men. Sertoli cell function, as determined by inhibin production, was more diminished in the elderly men than was Leydig cell function. These data strengthen the hypothesis that normal aging in men is accompanied by a decline in testicular function.
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Findings suggest reduced responsiveness of the hypothalamic-pituitary-gonadal axis in elderly males, which must be accounted for when comparing studies of men of differing ages.
“Findings suggested reduced responsiveness of the hypothalamic-pituitary-gonadal axis in elderly males, an effect, which must be accounted for in comparing studies of men with differing ages.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [128]
In a prospective study, young and elderly men treated with clomiphene citrate 50 mg/day for two months showed an approximately 870 ng/dL increase in the youthful group versus 489 ng/dL in elderly males.
“Tenover and colleagues prospectively treated young and elderly (mean age 29 years vs. 73 years) men with clomiphene citrate 50mg/day for two months.128 Results demonstrated an approximately 870ng/dl (30.2 nmol/L) increase in the youthful group compared to 489ng/dl (17 nmol/L) in elderly males.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [128]
Experimental studies demonstrate reduced LH and testosterone secretion in response to SERMs or AIs in older compared to young men.
“Experimental studies demonstrate reduced LH and testosterone secretion in response to SERMs 27,72 or AIs 107 in older compared to young men,”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [72]
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- Authors
- TENOVER, J. S., & BREMNER, W. J.
- Affiliations
- Veterans Health Administration (US)
- ORCID
- BREMNER, WILLIAM J.
- Venue
- Journal of Andrology
- Publisher
- Wiley
- Published
- 1991-07-08
- Volume
- 12
- Issue
- 4
- Pages
- 258-263
- ISSN
- 0196-3635 (ISSN-L)
- 1939-4640
- OpenAlex
- W1507402038
- Cited by
- 41
- References
- 29
- Citations by year
- 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Andrology (publishedVersion)
- PubMed (publishedVersion)
- ResearchWorks at the University of Washington (University of Washington) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- University of Washington
- National Institutes of Health (5k08ag000411-02)
- National Institute on Aging (K08AG00411)
- National Center for Research Resources (RR 37)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-12629)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- male aging, pituitary-gonadal axis, clomiphene citrate, gonadotropin stimulation, testosterone, estradiol, inhibin, luteinizing hormone, Sertoli cell function, Leydig cell function, testicular dysfunction, older men, androgen decline
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Analysis of Variance, Clomiphene, Gonadotropins, Humans, Luteinizing Hormone, Male, Pituitary Gland, Pulsatile Flow, Gonadal Steroid Hormones, Testis
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