Changes In Sperm Production And Reproductive Physiology Associated With Aging

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From a presentation a symposium titled, "Infertility in the Older Male Desiring Children" held at the annual meeting of the Society for the Study of Male Reproduction.

Presenter: Antoine Makhlouf, MD,
Department of Urologic Surgery,
University of Minnesota, Minneapolis

 
Does a man's ability to father children decrease with age? Interest in this question is increasing because of longer life expectancy, later age of parenting, and possibly declining sperm counts due to environmental factors. This seemingly simple question, however, does not have a simple answer.
 
There are no large longitudinal studies of semen quality. Smaller studies have found no decrease in counts or concentration, but a decrease in volume and a drop in motility.1-3 Whether these changes translate to decreased fertility is difficult to determine. Most studies, when controlled for female age, have found decreased fecundity among older men.1 For example, one county-wide survey in England found that the odds of initiating a planned pregnancy within 12 months were two-fold lower in men over 40 than men under 25.4
 
Testicular changes with age are well documented. Overall volume seems to stay constant well into the 7th decade, at which point a decrease sets in.5 Changes at the histological level include a decrease in the number of Leydig and Sertoli cells, a thickening of the basement membrane of the seminiferous tubules,6 and an increase in arrested division of germ cells. These lead to a decreased efficacy of spermatogenesis, with fewer mature sperm produced per tubule.

These changes, however, exhibit a high degree of inter-subject variability, and some men seem to preserve apparently normal spermatogenesis well into their 90s.6 Ischemia due to advancing atherosclerosis and a decline in the function of the hypothalamic-pituitary-gonadal axis have been suggested as possible causes of the decline in spermatogenesis.
 
Changes in testosterone levels have been well documented in the Massachusetts Male Aging Study (MMAS), and confirmed by other longitudinal studies.7,8 Generally, total testosterone levels decline by 1%-2% per year. Concurrently, sex-hormone-binding globulin levels increase slightly, leading to a decrease in the free-androgen index. The drop in testosterone production is ascribed to a blunting of the pulsatility of gonadotropin secretion combined with decreased steroidogenic capacity of Leydig cells.

The relative decline in testosterone production can affect fertility at the testicular level, where very high androgen levels are required for spermatogenesis; at the excurrent glands level, where production of the maturation proteins found in seminal plasma is androgen driven; and at the level of sexual function. Other hormonal indices of sperm production exhibit changes. FSH rises from a mean of 3.5 mU/ml in men under 40, to over 10 mU/ml in men over 75. 
 
The effect of aging on ejaculatory function has not been studied extensively. The few studies available indicate that anejaculation, virtually absent in younger men, increases rapidly after age 60 so that in men over 70 one third are affected.9 This parallels and independently correlates with an increase in the severity of LUTS.10 In addition, treatments for BPH, both medical and surgical, often negatively affect ejaculatory function.

Even worse are treatments for prostate cancer which effectively render the patient sterile. Finally, libido exhibits a steady decline with advancing age. For example, the Health Professionals Follow-up Study showed that only 23% of those over 80 had a “good” or “very good” desire, compared to 70% of respondents under 60.11 This blunting of the sexual drive is clearly related to the drop in testosterone levels, although other factors, both organic and psychosocial, certainly play a role.
 

References

  1. Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001 Feb;75(2):237-48.
  2. Schwartz D, Mayaux MJ, Spira A, et al. Semen characteristics as a function of age in 833 fertile men. Fertil Steril. 1983 Apr;39(4):530-5.
  3. Nieschlag E, Lammers U, Freischem  CW, et al. Reproductive functions in young fathers and grandfathers. J Clin Endocrinol Metab. 1982 Oct;55(4):676-81.
  4. Ford WC, North K, et al. Increasing paternal age and delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. The ALSPAC Team (Avon Longitu-dinal Study of Pregnancy and Childhood). Hum. Reprod. 2000 Aug;15(8):1703-8.
  5. Kuhnert B, Nieschlag E. Reproductive functions of the aging male. Hum Reprod Update. 2004 Jul-Aug;10(4):327-39.
  6. Dakouane M, Bicchieray L, Bergere M, et al. A histomorphometric and cytogenetic study of testis from men 29-102 years old. Fertil Steril. 2005 Apr; 83(4):923-8.
  7. Feldman HA, Goldstein I, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994 Jan;151(1):54-61.
  8. Mohr BA, Guay AT, et al. Normal, bound and nonbound testosterone levels in normally aging men: results of the Massachusetts Male Aging Study. Clin Endocrinol (Oxf). 2005 Jan;62(1):64-73.
  9. Blanker MH, Bosch JL, Groeneveld FP, et al. Erectile and ejaculatory dysfunction in a community-based sample of men 50 to 78 years old: prevalence, concern, and relation to sexual activity. Urology. 2001 Apr;57(4):763-8.
  10. Rosen R, Altwein J, Boyle P, Kirby RS, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol. 2003 Dec;44(6):637-49.
  11. Bacon CG, Mittleman MA, Kawachi I, et al. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med. 2003 Aug 5;139(3):161-8.
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