The male biological clock is ticking

a review of the literature

Authors

  • Fabio Firmbach Pasqualotto Universidade de Caxias do Sul
  • Edson Borges Júnior Universidade de Caxias do Sul
  • Eleonora Bedin Pasqualotto Universidade de Caxias do Sul

Keywords:

Male, Erectile dysfunction, Infertility, Diabetes complications, Heart

Abstract

The term biological clock is usually used by physicians and psychologists to refer to the declining fertility, increasing risk of fetal birth defects and alterations to hormone levels experienced by women as they age. Female fecundity declines slowly after the age of 30 years and more rapidly after 40 and is considered the main limiting factor in treating infertility. However, there are several scientifi c reports, chapters in books and review articles suggesting that men may also have a biological clock. The aim of our study was to conduct a review of the literature, based on the Medical Literature Analysis and Retrieval System Online (Medline), to evaluate the male biological clock. After adjustments for other factors, the data demonstrate that the likelihood that a fertile couple will take more than 12 months to conceive nearly doubles from 8% when the man is < 25 years old to 15% when he is > 35 years old. Thus, paternal age is a further factor to be taken into account when deciding on the prognosis for infertile couples. Also, increasing male age is associated with a signifi cant decline in fertility (fi ve times longer to achieve pregnancy at the age of 45 years). Patients and their physicians therefore need to understand the effects of the male biological clock on sexual and reproductive health, in that it leads to erectile dysfunction and male infertility, as well as its potential implications for important medical conditions such as diabetes and cardiovascular diseases.

Downloads

Download data is not yet available.

Author Biographies

Fabio Firmbach Pasqualotto, Universidade de Caxias do Sul

MD, MSc, PhD. Professor of Urology and Embryology, Centro de Ciências Biológicas e da Saúde (CCBS), Universidade de Caxias do Sul (UCS), Caxias do Sul, Rio Grande do Sul, Brazil.

Edson Borges Júnior, Universidade de Caxias do Sul

MD, PhD. Director of the Sapientiae Association and Institute, São Paulo, Brazil.

Eleonora Bedin Pasqualotto, Universidade de Caxias do Sul

MD. PhD. Professor of Gynecology and Obstetrics, Centro de Ciências Biológicas e da Saúde (CCBS), Universidade de Caxias do Sul (UCS), Caxias do Sul, Rio Grande do Sul, Brazil.

References

Templeton A. Infertility-epidemiology, aetiology and effective management. Health Bull (Edinb). 1995;53(5):294-8.

Joffe M, Li Z. Male and female factors in fertility. Am J Epide- miol. 1994;140(10):921-9.

Lansac J. Delayed parenting. Is delayed childbearing a good thing? Hum Reprod. 1995;10(5):1033-5.

Pal L, Santoro N. Age-related decline in fertility. Endocrinol Metab Clin North Am. 2003;32(3):669-88.

Pasqualotto FF, Sobreiro BP, Hallak J, Pasqualotto EB, Lucon AM. Sperm concentration and normal sperm morphology decrease and follicle-stimulating hormone level increases with age. BJU Int. 2005;96(7):1087-91.

Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med. 2004;350(5):482-92.

Jensen TK, Jorgensen N, Punab M, et al. Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries. Am J Epidemiol. 2004;159(1):49-58.

Handelsman DJ. Sperm output of healthy men in Australia: magnitude of bias due to self-selected volunteers. Hum Reprod. 1997;12(12):2701-5.

Cohn BA, Overstreet JW, Fogel RJ, Brazil CK, Baird DD, Cirillo PM. Epidemiologic studies of human semen quality: consider- ations for study design. Am J Epidemiol. 2002;155(7):664-71.

Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on se- men quality and fertility: a review of the literature. Fertil Steril. 2001;75(2):237-48.

Ford WC, North K, Taylor H, Farrow A, Hull MG, Golding

J. Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. The ALSPAC Study Team (Avon Lon- gitudinal Study of Pregnancy and Childhood). Hum Reprod. 2000;15(8):1703-8.

Eskenazi B, Wyrobek AJ, Sloter E, et al. The association of age and semen quality in healthy men. Hum Reprod. 2003;18(2):447-54.

Hassan MA, Killick SR. Effect of male age on fertility: evidence for the decline in male fertility with increasing age. Fertil Steril. 2003;79(Suppl 3):1520-7.

Neaves WB, Johnson L, Porter JC, Parker CR Jr, Petty CS. Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men. J Clin Endocrinol Metab. 1984;59(4):756-63.

Dallinga JW, Moonen EJ, Dumoulin JC, Evers JL, Geraedts JP, Kleinjans JC. Decreased human semen quality and organochlo- rine compounds in blood. Hum Reprod. 2002;17(8):1973-9.

Oldereid NB, Thomassen Y, Attramadal A, Olaisen B, Purvis

K. Concentrations of lead, cadmium and zinc in the tissues of reproductive organs of men. J Reprod Fertil. 1993;99(2):421-5.

Oldereid NB, Thomassen Y, Purvis K. Selenium in human male reproductive organs. Hum Reprod. 1998;13(8):2172-6.

Handelsman DJ, Staraj S. Testicular size: the effects of aging, malnutrition, and illness. J Androl. 1985;6(3):144-51.

Mahmoud AM, Goemaere S, El-Garem Y, Van Pottelbergh I, Comhaire FH, Kaufman JM. Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men. J Clin Endocrinol Metab. 2003;88(1):179-84.

Harbitz TB. Morphometric studies of the Sertoli cells in elderly men with special reference to the histology of the prostate. An analysis in an autopsy series. Acta Pathol Microbiol Scand [A]. 1973;81(5):703-14.

Johnson L. Spermatogenesis and aging in the human. J Androl. 1986;7(6):331-54.

Paniagua R, Amat P, Nistal M, Martin A. Ultrastructure of Ley- dig cells in human ageing testes. J Anat. 1986;146:173-83.

Paniagua R, Nistal M, Amat P, Rodriguez MC, Martin A. Seminiferous tubule involution in elderly men. Biol Reprod. 1987;36(4):939-47.

Regadera J, Nistal M, Paniagua R. Testis, epididymis, and spermatic cord in elderly men. Correlation of angiographic and histologic studies with systemic arteriosclerosis. Arch Pathol Lab Med. 1985;109(7):663-7.

Hermann M, Untergasser G, Rumpold H, Berger P. Aging of the male reproductive system. Exp Gerontol. 2000;35(9- 10):1267-79.

Mathieu C, Ecochard R, Bied V, Lornage J, Czyba JC. Cumula- tive conception rate following intrauterine artificial insemination with husband’s spermatozoa: influence of husband’s age. Hum Reprod. 1995;10(5):1090-7.

Seymour FI, Duffy C, Koerner A. A case of authenticated fertility in a man, aged 94. J Am Med Assoc. 1935;105:1423-4.

Pasqualotto FF, Locambo CV, Athayde KS, Arap S. Measuring male infertility: epidemiological aspects. Rev Hosp Clin Fac Med Sao Paulo. 2003;58(3):173-8.

de la Rochebrochard E, Thonneau P. Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod. 2002;17(6):1649-56.

Dunson DB, Colombo B, Baird DD. Changes with age in the level and duration of fertility in the menstrual cycle. Hum Reprod. 2002;17(5):1399-403.

Dunson DB, Baird DD, Colombo B. Increased infertility with age in men and women. Obstet Gynecol. 2004;103(1):51-6.

Rolf C, Behre HM, Nieschlag E. Reproductive parameters of older compared to younger men of infertile couples. Int J Androl. 1996;19(3):135-42.

Spandorfer SD, Avrech OM, Colombero LT, Palermo GD, Ros- enwaks Z. Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection. Hum Reprod. 1998;13(2):334-8.

Piette C, de Mouzon J, Bachelot A, Spira A. In-vitro fertilization: influence of women’s age on pregnancy rates. Hum Reprod. 1990;5(1):56-9.

Gallardo E, Simón C, Levy M, Guanes PP, Remohí J, Pellicer

A. Effect of age on sperm fertility potential: oocyte donation as a model. Fertil Steril. 1996;66(2):260-4.

Paulson RJ, Milligan RC, Sokol RZ. The lack of influence of age on male fertility. Am J Obstet Gynecol. 2001;184(5):818-22; discussion 822-4.

Brzechffa PR, Buyalos RP. Female and male partner age and menotrophin requirements influence pregnancy rates with hu- man menopausal gonadotrophin therapy in combination with intrauterine insemination. Hum Reprod. 1997;12(1):29-33.

Hellstrom WJ, Overstreet JW, Sikka SC, et al. Semen and sperm reference ranges for men 45 years of age and older. J Androl. 2006;27(3):421-8.

Lambert SM, Masson P, Fisch H. The male biological clock. World J Urol. 2006;24(6):611-7.

British Andrology Society. British Andrology Society guidelines for the screening of semen donors for donor insemination (1999). Hum Reprod. 1999;14(7):1823-6.

Kühnert B, Nieschlag E. Reproductive functions of the ageing male. Hum Reprod Update. 2004;10(4):327-39.

Sloter E, Schmid TE, Marchetti F, Eskenazi B, Nath J, Wyrobek AJ. Quantitative effects of male age on sperm motion. Hum Reprod. 2006;21(11):2868-75.

Wyrobek AJ, Aardema M, Eichenlaub-Ritter U, Ferguson L, Marchetti F. Mechanisms and targets involved in maternal and paternal age effects on numerical aneuploidy. Environ Mol Mutagen. 1996;28(3):254-64.

Reichenberg A, Gross R, Weiser M, et al. Advancing paternal age and autism. Arch Gen Psychiatry. 2006;63(9):1026-32.

Malaspina D, Harlap S, Fennig S, et al. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry. 2001;58(4):361-7.

Fisch H, Hyun G, Golden R, Hensle TW, Olsson CA, Liberson GL. The influence of paternal age on down syndrome. J Urol. 2003;169(6):2275-8.

Pasqualotto FF, Lucon AM, Hallak J, Pasqualotto EB, Arap S. Risks and benefits of hormone replacement therapy in older men. Rev Hosp Clin Fac Med Sao Paulo. 2004;59(1):32-8.

Gray A, Berlin JA, McKinlay JB, Lonqcope C. An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis. J Clin Epidemiol. 1991;44(7):671-84.

Vermeulen A. Clinical review 24: Androgens in the aging male. J Clin Endocrinol Metab. 1991;73(2):221-4.

Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86(2):724-31.

Tenover JL. Male hormone replacement therapy includ- ing “andropause”. Endocrinol Metab Clin North Am. 1998;27(4):969-87; x.

Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994;151(1):54-61.

Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006;91(6):1995-2010.

Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166(15):1660-5.

Marks LS, Mazer NA, Mostaghel E, et al. Effect of testosterone replacement therapy on prostate tissue in men with late- onset hypogonadism: a randomized controlled trial. JAMA. 2006;296(19):2351-61.

The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group. Ann Intern Med. 1995;122(8):561-8.

Grundy SM. Metabolic syndrome: connecting and reconcil- ing cardiovascular and diabetes worlds. J Am Coll Cardiol. 2006;47(6):1093-100.

Wei M, Macera CA, Davis DR, Hornung CA, Nankin HR, Blair SN. Total cholesterol and high density lipoprotein cholesterol as important predictors of erectile dysfunction. Am J Epidemiol. 1994;140(10):930-7.

Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moin- pour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005;294(23):2996-3002.

Araujo AB, Durante R, Feldman HA, Goldstein I, McKinlay JB. The relationship between depressive symptoms and male erectile dysfunction: cross-sectional results from the Massachusetts Male Aging Study. Psychosom Med. 1998;60(4):458-65.

Calais Da Silva F, Marquis P, Deschaseaux P, Gineste JL, Cauquil J, Patrick DL. Relative importance of sexuality and quality of life in patients with prostatic symptoms. Results of an international study. Eur Urol. 1997;31(3):272-80.

Downloads

Published

2008-05-05

How to Cite

1.
Pasqualotto FF, Borges Júnior E, Pasqualotto EB. The male biological clock is ticking: a review of the literature. Sao Paulo Med J [Internet]. 2008 May 5 [cited 2025 Mar. 14];126(3):197-201. Available from: https://periodicosapm.emnuvens.com.br/spmj/article/view/1973

Issue

Section

Review Article