Skip to main content

L'andropause

Andropause

Resume

Au cours du vieillissement, une altération de l'axe hypothalamo-hypophysotesticulaire a été identifiée. Une diminution très progressive de la testostérone plasmatique a été mise en évidence, indépendamment de phénomènes pathologiques. Elle est due à une altération testiculaire périphérique, comme le montrent la diminution de la réponse à l'hCG, l'augmentation de la LH, et la diminution du nombre de cellules de Leydig. L'augmentation progressive de la protéine de transport plasmatique des stéroïdes sexuels, la SHBG, explique une diminution encore plus nette de la testostérone biodisponible. Des études précises de la sécrétion gonadotrope montrent l'association à l'altération testiculaire d'une insuffisance gonadotrope relative partielle. Le testicule exocrine subit aussi une altération avec l'âge, avec augmentation de la concentration de FSH, diminution de l'inhibine, du nombre de cellules de Sertoli et de la production de spermatozoïdes. Si l'incidence des perturbations de la sexualité augmente avec le vieillissement, la corrélation entre niveau d'androgènes et sexualité n'apparaît que faible dans les études épidémiologiques, en raison du caractère multifactoriel de la sexualité humaine et de l'existence d'un seuil au-dessus duquel les androgènes n'augmentent plus l'activité sexuelle. La question des risques propres de l'androgénothérapie substitutive de l'hypogonadisme lié à l'âge reste posée. Si un effet positif sur un sensation générale de bien-être et sur la libido et l'absence d'effet néfaste sur les paramètres du métabolisme glucidique et lipidique ont été démontrés dans des études à court terme, le rôle exact des stéroïdes dans la genèse de l'hypertrophie bénigne de la prostate et dans la possible progression de microcarcinomes prostatiques reste méconnu. Des études complémentaires apparaissent nécessaires pour mieux préciser le rapport bénéfices/risques d'une androgénothérapie substitutive à long terme chez l'homme âgé.

Abstract

In men, aging is associated with progressive impairment of testicular function. Decrease in total testosterone levels with aging has been reported in many studies in normal healthy men. This decrease has a primarily testicular origin, as shown by decreased number of Leydig cells in histological studies, increased basal gonadotropin levels and decreased response to hCG. A greater decrease in bioavailable testosterone rather in than total testosterone concentrations is explained by the age-dependent increase in the SHBG concentration. Although immunoreactive gonadotropin levels are higher than in young men, a relative alteration of bioactive gonadotropin secretion by the pituitatry occurs in ederly men. Althought the definitive demonstration of an alteration of GnRH secretion by the hypothalamus cannot be established in healthy ederly men, such an alteration might be responsible for a decompensation of the testicular function in case of intercurrent illness. Increased FSH and decreased inhibin plasma levels are indicating a similar alteration in seminiferous tubules as directly demonstrated by histological data showing a decrease of Sertoli cell number and daily sperm production with aging. Although the incidence of sexual dysfunction increases with aging, the relationship between sexual behaviour and testicular endocrine function remained a mater of controversy. A threshold of testosterone action on sexual behavior might be responsible for the difficulty in establishing this relationship. Although some controled studies are available, the risk-to-benefit balance of androgen substitution in older male remained a controversial issue. A positive effect on sense of well-being and/or libido has been and the lack of adverse effect on lipid and carbohydrate metabolism had been demonstrated in short term studies, however, the role of androgens in the benign hypertrophy of the prostate and in stimulating the growth of latent prostate adenocarcinoma remained to be more clearly established by longterm controlled studies.

References

  1. AUROUX M., NAWAR N.N.Y., RIZKALLA N.: Testicular aging: vascularization and gametogenesis modifications in the Wistar rat. Arch. Androl., 1985, 14: 115–121.

    PubMed  Article  CAS  Google Scholar 

  2. BAGATELL C.J., HEIMAN J.R., RIVIER J.E., BREMNER W.J.: Effects of endogenous testosterone and estradiol on sexual behavior in normal young men. J. Clin. Endocrinol. Metab., 1994, 78: 711–716.

    PubMed  Article  CAS  Google Scholar 

  3. BARDIN C.W., SWERDLOFF R.S., SANTEN R.J.: Androgens: risks and benefits. J. Clin. Endocrinol. Metab. 1991, 73: 4–7.

    PubMed  CAS  Google Scholar 

  4. BREMNER W.J., VITIELLO M.V., PRINZ P.N.: Loss of circadian rythmicity in blood testosterone levels with aging in normal men. J. Clin. Endocrinol. Metab. 1983, 56: 1278–1281.

    PubMed  CAS  Google Scholar 

  5. CORPAS E., HARMAN S.M., BLACKMAN M.R.: Human growth hormone and human aging. Endocrine Rev., 1993, 14: 20–39.

    CAS  Google Scholar 

  6. DAVIDSON J.M., CAMARGO C.A., SMITH E.R.: Effects of androgen on sexual behavior in hypogonadal men. J. Clin. Endocrinol. Metab., 1979, 48: 955–958.

    PubMed  CAS  Google Scholar 

  7. DAVIDSON J.M., CHEN J.J., CRAPO L., GRAY G.D., GREENLEAF W.J., CATANIA J.A.: Hormonal changes and sexual function in aging men. J. Clin. Endocrinol. Metab., 1983, 57: 71–77.

    PubMed  CAS  Google Scholar 

  8. DECHAUD H., LEJEUNE H., GAROSCIO-CHOLET M., MALLEIN R., PUGEAT M.: Radioimmunoassay of testosterone not bound to sex-steroidbinding protein in plasma. Clin. Chem., 1989, 35: 1609–1614.

    PubMed  CAS  Google Scholar 

  9. DE LIGNIERES B.: Transdermal dihydrotestosterone treatment of “andropause”. Ann. Med., 1993, 25: 235–241.

    PubMed  Article  Google Scholar 

  10. DESLYPERE J.P., VERMEULEN A.: Leydig cell function in normal men: effect of age, life-style, residence, diet and activity. J. Clin. Endocrinol. Metab., 1984, 59: 955–962.

    PubMed  CAS  Google Scholar 

  11. DESLYPERE J.P., KAUFMAN J.M., VERMEULEN T., VOGELAERS D., VANDALEM J.L., VERMEULEN A.: Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men. J. Clin. Endocrinol. Metab., 1987, 64: 68–73.

    PubMed  CAS  Google Scholar 

  12. HARMAN S.M., TSITOURAS P.D., COSTA P.T., BLACKMAN M.R.: Reproductive hormones in aging male. II. Basal pituitary gonadotropins and gonadotropin responses to luteinizing hormonereleasing hormone. J. Clin. Endocrinol. Metab., 1982, 54, 547–551.

    PubMed  CAS  Google Scholar 

  13. ISAACS J.T., COFFEY D.S.: Etiology and disease process of benign prostatic hyperplasia. Prostate, 1989, 2: 33–50.

    Article  CAS  Google Scholar 

  14. JOHNSON L., ZANE R., PETTY C.S., NEAVES W.B.: Quantification of human Sertoli cell population: its distribution, relation to germ cell number, and age-related decline. Biol. Reprod., 1984, 31: 785–795.

    PubMed  Article  CAS  Google Scholar 

  15. KINSEY A.C., POMEROY W.E., MARTIN C.E., GEBHARD P.H.: Sexual behavior in the human male. edited by WB Saunders, Philadelphia, 1948.

  16. KWAN M., GREENLEAF W.J., MANN J., CRAPO L., DAVIDSON J.M.: The nature of androgen action on male sexuality: a combined laboratoryself-report study on hypogonadal men. J. Clin. Endocrinol. Metab., 1983, 57: 557–562.

    PubMed  CAS  Google Scholar 

  17. LEJEUNE H., MOCKUS I., CHARRIE A., MAZENOD B., PUGEAT M., TOURNIAIRE J.: Analyse de la pulsatilité de LH: importance de l'estimation des faux négatifs. Rev. Franç. Endocrinol. Clin., 1988, 29: 563–572.

    Google Scholar 

  18. LEWIS J.G., GHANADIAN R., CHISHOLM G.D. Serum 5a-dihydrotestosterone and testosterone, changes with age in man. Acta Endocrinol. (Copenh), 1976, 82: 444–448.

    CAS  Google Scholar 

  19. MARIN P., KROTKIEWSKI M., BJORNTROP P.: Androgen treatment of middle-aged, obese men: effects on metabolism and adipose tissues. Eur. J. Med., 1992, 1: 329–336.

    PubMed  CAS  Google Scholar 

  20. MASTUMOTO A.M.: Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose of dependent suppression of luteinizing hormone, follicle stimulating hormone and sperm production. J. Clin. Endocrinol. Metab. 1990, 70: 282–287.

    Google Scholar 

  21. MEIKLE A.W., STANISH W.M., TAYLOR N., EDWARDS C., BISHOP D.T.: Familial effects on plasma sex-steroid content in man: testosterone, estradiol and sex hormone-binding-globulin. Metabolism, 1982, 31: 6–9.

    PubMed  CAS  Google Scholar 

  22. MORALES A.J., NOLAN J.J., NELSON J.C., YEN S.S.C.: Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J. Clin. Endocrinol. Metab., 1994, 78: 1360–1367.

    PubMed  Article  CAS  Google Scholar 

  23. MUTA K., KATO K., AKAMINE Y., IBAYASHI H.: Age-related changes in the feedback regulation of gonadotrophin secretion by sex steroids in men. Acta Endocrinol. (Copenh), 1981, 96: 154–162.

    CAS  Google Scholar 

  24. NEAVES W.B., JOHNSON L., PORTER J.C., PARKER C.R., PETTY C.S.: Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men. J. Clin. Endocrinol. Metab., 1984, 59: 756–763.

    PubMed  CAS  Google Scholar 

  25. O'CARROLL R., SHAPIRO C., BANCROFT J.: Androgens, Behaviour and norcturnal erection in hypogonadal men: the effects of varying the replacement dose. Clin. Endocrinol. (Oxf), 1985, 23: 527–538.

    Article  Google Scholar 

  26. ORENTREICH N., BRIND J.L., RIZER R.L., VOGELMAN J.H.: Age changes ans sex differences in serum Dehydroepiandrosterone sulfate concentrations throughout Adulthood. J. Clin. Endocrinol. Metab., 1984, 59: 551–555.

    PubMed  CAS  Google Scholar 

  27. PIRKE K.M., DOERR P.: Age related changes and interrelationships between plasma testosterone, oestradiol and testosterone-binding globulin in normal adult males. Acta Endocrinol. (Copenh), 1974, 74: 792–800.

    Google Scholar 

  28. REITER T.: Testosterone implantation: a clinical study of 240 implantations in aging males. J. Am. Geriatr. Soc. 1963, 11: 540–550.

    PubMed  CAS  Google Scholar 

  29. RUBENS R., DHONT M., VERMEULEN A.: Further studies on Leydig cell function in old age. J. Clin. Endocrinol. Metab., 1974, 39: 40–45.

    PubMed  CAS  Google Scholar 

  30. SAEZ JM.: Leydig cells: Endocrine, paracrine, and autocrine regulation. Endocrine Rev., 1994, 15: 574–626.

    CAS  Google Scholar 

  31. SEYMOUR F.I., DUFFY C., KŒRNER A.: A case of authenticated fertility in a man of 94. J.A.M.A., 1935, 105: 1423–1424.

    Google Scholar 

  32. SIMON D., PREZIOSI P., BARRETT-CONNOR E., ROGER M., SAINT-PAUL M., NAHOUL K., PAPOZ L.: The influence of aging on plasma sex hormone in men: the telecom study. Am. J. Epidemiol., 1992, 135: 783–791.

    PubMed  CAS  Google Scholar 

  33. TAKIZAWA T., HATAKEYAMA S.: Age associated changes in microvasculature of human adult testis. Acta Path. Jap., 1978, 28: 541–554.

    PubMed  CAS  Google Scholar 

  34. TENOVER J.S., MATSUMOTO A.M., PLYMATE S.R., BREMNER W.J.: The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate. J. Clin. Endocrinol. Metab., 1987, 65: 1118–1126.

    PubMed  CAS  Google Scholar 

  35. TENOVER J.S., DAHL K.D., HSUEH A.J.W., LIM P., MATSUMOTO A.M., BREMNER W.J.: Serum bioactive and immunoreactive follicle-stimulating hormone levels and the response to clomiphene in healthy young and elderly men. J. Clin. Endocrinol. Metab., 1987, 64: 1103–1108.

    PubMed  CAS  Google Scholar 

  36. TENOVER J.S., McLACHLAN R.I., DAHL K.D., BURGER H.G., DE KRETSER D.M., BREMNER W.J.: Decreased serum inhibin levels in normal elderly men: evidence for a decline in Sertoli cell function with aging. J. Clin. Endocrinol. Metab., 1988, 67: 455–459.

    PubMed  CAS  Google Scholar 

  37. TENOVER J.S.: Effects of testosterone supplementation in the aging male. J. Clin. Endocrinol. Metab., 1992, 75: 1092–1098.

    PubMed  Article  CAS  Google Scholar 

  38. URBAN R.J., VELDHUIS J.D., BLIZZARD R.M., DUFAU M.L.: Attenuated release of biologically active luteinizing hormone in healthy aging men. J. Clin. Invest., 1988, 81: 1020–1029.

    PubMed  Article  CAS  Google Scholar 

  39. VERMEULEN A., DESLYPERE J.P., KAUFMAN J.M.: Influence of antiopioids on luteinizing hormone pulsatility in aging men. J. Clin. Endocrinol. Metab., 1989, 68: 68–72.

    PubMed  CAS  Google Scholar 

  40. VERMEULEN A., RUBENS R., VERDONCK L.: Testosterone secretion and metabolism in male senescence. J. Clin. Endocrinol. Metab., 1972, 34: 730–735.

    PubMed  CAS  Google Scholar 

  41. WARNER B.A., DUFAU M.L., SANTEN R.J.: Effects of aging and illness on the pituitary testicular axis in men: qualitative as well as quantitative changes in luteinizing hormone. J. Clin. Endocrinol. Metab., 1985, 60: 263–268.

    PubMed  CAS  Google Scholar 

  42. WINTERS S.J., TROEN P.: Episodic luteinizing hormone (LH) secretion and the response of LH and follicle-stimulating hormone to LH-releasing hormone in aged men: evidence for coexistent primary testicular insufficiency and an impairment in gonadotropin secretion. J. Clin. Endocrinol. Metab., 1982, 55: 560–565.

    PubMed  CAS  Google Scholar 

  43. WiNTERS S.J., SHERINS R.J., TROEN P.: The gonadotropin-suppressive activity of androgen is increased in eldrely men. Metabolism, 1984, 33: 1052–1059.

    PubMed  Article  CAS  Google Scholar 

  44. ZUMOFF B., STRAIN G.W., KREAM J., O'CONNOR J., ROSENFELD R.S., LEVIN J., FUKUSHIMA D.K.: Age variation of the 24-hour mean plasma concentrations of androgens, estrogens and gonadotropins in normal adult men. J. Clin. Endocrinol. Metab., 1982, 54: 534–538.

    PubMed  CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lejeune, H. L'andropause. Androl. 7, 66–75 (1997). https://doi.org/10.1007/BF03034520

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03034520

Mots clés

  • andropause
  • vieillissement
  • testicule
  • testostérone

Key words

  • andropause
  • aging
  • testosterone
  • testis