Ageing of the Hypothalamo-Pituitary- Testicular Axis in Men
Abstract
In distinction to the course of reproductive ageing in women, men do not experience a rapid decline of Leydig cell function or irreversible arrest of reproductive capacity in old age. Hence, strictu sensu, the andropause does not exist. Nevertheless, both spermatogenesis and fertility as well as Leydig cell function do decline with age, as shown by a decrease of ± 35% of total and of 50% of free testosterone levels between the age of 20 and 80 years. The origin of this decline of Leydig cell function resides on the one hand in the testes, and is essentially characterized by a decreased number of Leydig (and Sertoli) cells and on the other hand in the hypothalamo-pituitary complex characterized by a decreased luteinzing hormone (LH) pulse amplitude, LH pulse frequency being maintained. As the responsiveness of the gonadotrophs to gonadotropin-releasing hormone (GnRH) remains unimpaired, one may assume that the amount of GnRH released at each pulse is also reduced, possibly as the consequence of a reduction of the cellular mass of GnRH neurones. Plasma levels of testosterone below the lower normal limit occur, however, only in a minority of elderly men from 7% in the age group 40-60, to 20% in the age group 60-80 and 35% in the age group over 80 years old. Factors influencing testosterone levels in elderly men are multiple: hereditary, environmental (obesity, stress), psychosocial (depression, smoking, drugs) or socioeconomical (diet, hygiene). Whether these elderly men should be substituted with androgens remains controversial. Beneficial effects, such as an increased feeling of well-being and fitness, increased muscle strength and endurance, decreased bone catabolism and increase of hematocrit, should be weighed against the risks of stimulation of growth of an occult, subclinical prostatic carcinoma (occurring with a high frequency in elderly males). Therefore, large scale androgen supplementation should await the results of well-controlled prospective studies.
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The prevalence of overt biochemical hypogonadism in 830 men with proven coronary artery disease at angiography was 23.4%, approximately three times higher than the background healthy community prevalence.
“the overall prevalence of overt biochemical hypogonadism in 830 men with proven coronary artery disease at angiography was 23.4%, 9 which is approximately three times higher than the background healthy community prevalence.10”
From Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life (2004) · cites this paper as [10]
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“A IN RODENTS and men is associated with reduced serum testosterone concentration (1, 2).”
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“Indeed, obese men are more likely to be hypogonadal, perhaps because of increased aromatization of testosterone to estradiol in peripheral fat tissue [10] and alterations of the hypothalamic–pituitary–testicular axis [11, 12].”
BackgroundThe complex association between metabolic syndrome and male hypogonadism
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“Some reage.[12] When considering free testosterone, 60% of searchers argue that the relationship between low very healthy men between the age of 60 and 80 testosterone levels and the nonspecific physical, years, evaluated by one laboratory, were hypotestos- sexual and emotional states attributed to testosterteronemic…”
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EMAS position statement: Testosterone replacement therapy in the aging male
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The biological meaning of preferences on the human mate market
Pawłowski, B. (2000) · Anthropological Review · doi:10.18778/1898-6773.63.04 · Cited by 55 · see citing works
“Despite the fact that reproductive potentials also decrease with age for males [VERMEULEN & KAUFMAN 1995; VERMEULEN 2000], their age is rather more important in relation to the decrease of their further life expectancy.”
BackgroundNegative association of testosterone on spatial visualization in 35 to 80 year old men.
Yonker, J., Eriksson, E., Nilsson, L., & Herlitz, A. (2006) · Cortex; a journal devoted to the study of the nervous system and behavior · doi:10.1016/s0010-9452(08)70364-2 · Cited by 60 · see citing works
“As men age, their circulating androgen levels decline (Gray et al., 1991; Vermeulen and Kaufman, 1995; Lamberts et al., 1997; Sternbach, 1998), thereby supplying less active androgen that could influence cognitive functioning.”
BackgroundThe Male Menopause and Mood: Testosterone Decline and Depression in the Aging Male—Is There a Link?
Margolese, H. C. (2000) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198870001300208 · Cited by 54 · see citing works
Smith, A. M., English, K. M., Malkin, C. J., Jones, R. D., Jones, T. H., & Channer, K. S. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01848 · Cited by 51 · see citing works
Perry, P. J., Lund, B. C., Arndt, S. V., Holman, T. L., Bever‐Stille, K. A., Paulsen, J. S., & Demers, L. M. (2001) · Annals of Clinical Psychiatry · doi:10.1023/a:1016663523579 · Cited by 56 · see citing works
“below the normal lower limit (350 ng/dL) (2).”
BackgroundSperm count and sperm motility decrease in old rats
Lucio, R. A., Tlachi-López, J. L., Eguibar, J. R., & Ågmo, A. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.12.015 · Cited by 49 · see citing works
Relationship of Age, Age at Onset, and Sex to Depression in Older Adults
Lavretsky, H., Lesser, I. M., Wohl, M. A., & Miller, B. L. (1998) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-199800630-00007 · Cited by 56 · see citing works
Views From Within and Beyond: Narratives of Cardiac Contractile Dysfunction Under Senescence
Yang, X., Sreejayan, N., & Ren, J. T. (2005) · Endocrine · doi:10.1385/endo:26:2:127 · Cited by 48 · see citing works
Relationship between testosterone and erectile dysfunction.
Rajfer, J. (2000) · Europe PMC (PubMed Central) · Cited by 47 · see citing works
31st G. Heiner Sell Lectureship: Secondary Medical Consequences of Spinal Cord Injury
Bauman, W. A., Korsten, M. A., Radulovic, M., Schilero, G. J., Wech, J., & Spungen, A. M. (2012) · Topics in Spinal Cord Injury Rehabilitation · doi:10.1310/sci1804-354 · Cited by 47 · see citing works
“The etiology of this progressive fall in serum testosterone is multi-factorial and, in part, attributable to various combinations of lifestyle choices, illness, medications, and inappropriate activity of the hypothalamic-pituitary-gonadal axis.(25,31,32) Decreased testosterone levels in the general population are asso…”
BackgroundMartínez-Jabaloyas, J. M., Zaragoza, A. Q., Rodríguez-Navarro, R., Queipo-Zaragozá, J. A., Gil‐Salom, M., & Chuan-Nuez, P. (2007) · European Urology · doi:10.1016/j.eururo.2007.05.021 · Cited by 46 · see citing works
Endocrine Responses to Chronic Androstenedione Intake in 30- to 56-Year-Old Men
Brown, G. A., Vukovich, M. D., Martini, E. R., Kohut, M. L., Franke, W. D., Jackson, D. A., & King, D. S. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6940 · Cited by 49 · see citing works
“ginning in the fifth (9) or sixth ( 8 ) decades of life, whereas others report relatively stable serum total testosterone concentrations through the seventh decade of life (7).”
BackgroundAndrogens, cardiovascular risk factors and atherosclerosis
von Eckardstein, A. (1998) · Springer eBooks · doi:10.1007/978-3-642-72185-4_8 · Cited by 45 · see citing works
Yang, H., Chryssikos, T. J., Houseni, M., Alzeair, S., Sansovini, M., Iruvuri, S., Torigian, D. A., Zhuang, H., Dadparvar, S., Basu, S. K., et al. (2010) · Molecular Imaging and Biology · doi:10.1007/s11307-010-0341-x · Cited by 46 · see citing works
“It is believed that the effects of aging on the testes in healthy men are mediated primarily through alterations of the hypothalamo–pituitary–testicular axis [ 6 ].”
BackgroundIs there a neuroendocrinological rationale for testosterone as a therapeutic option in depression?
Ebinger, M., Sievers, C., Ivan, D., Schneider, H., & Stalla, G. K. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108092337 · Cited by 45 · see citing works
“However, testosterone levels are age-dependent and men in their seventh decade have mean plasma testosterone levels that are 35% lower compared with those in young men, and more than 25% of men over the age of 75 years are ‘testosteronedeficient’ (Vermeulen and Kaufman, 1995).”
BackgroundThe effect of age on the expression of apoptosis biomarkers in human spermatozoa
Colin, A., Barroso, G., Gomez‐Lopez, N., et al. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.04.043 · Cited by 45 · see citing works
A sex difference in neurodegeneration of the human hypothalamus
Schultz, C., Braak, H., & Braak, E. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12787-7 · Cited by 45 · see citing works
Testosterone for secondary prevention in men with ischaemic heart disease?
Malkin, C. J., Pugh, P. J., Jones, T. H., & Channer, K. S. (2003) · QJM · doi:10.1093/qjmed/hcg086 · Cited by 45 · see citing works
The Relationship between Testosterone and Sexual Function in Depressed and Healthy Men
Rizvi, S. J., Kennedy, S. H., Ravindran, L. N., Giacobbe, P., Eisfeld, B. S., Mancini, D., & McIntyre, R. S. (2009) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2009.01504.x · Cited by 44 · see citing works
Diagnosis and management of testosterone deficiency
Coward, R. M., McBride, J., & Carson, C. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.143317 · Cited by 44 · see citing works
Cekic, M. M., & Stein, D. G. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2009.10.017 · Cited by 42 · see citing works
Association of endogenous sex hormone with C‐reactive protein levels in middle‐aged and elderly men
Nakhai-Pour, H. R., Grobbee, D. E., Muller, M., & van der Schouw, Y. T. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02745.x · Cited by 42 · see citing works
- Authors
- Vermeulen, A., & Kaufman, J. M.
- Affiliations
- Ghent University Hospital (BE)
- Venue
- Hormone Research
- Publisher
- S. Karger AG
- Published
- 2008-12-05
- Volume
- 43
- Issue
- 1-3
- Pages
- 25-28
- ISSN
- 0301-0163 (ISSN-L)
- 1423-0046
- OpenAlex
- W2025587852
- Cited by
- 265
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 8 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 8
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormone Research (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- 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
- andropause, Leydig cell function, spermatogenesis, male fertility, free testosterone, luteinizing hormone pulsatility, GnRH neurons, testosterone replacement therapy, older men
- MeSH terms
- Adult, Aged, Aging, Androgens, Hormones, Humans, Hypogonadism, Hypothalamo-Hypophyseal System, Leydig Cells, Luteinizing Hormone, Male, Middle Aged, Testis
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