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Déficit Androgénique Lié à l’Age

Androgen deficiency in the aging male

Résumé

L’amélioration de l’espérance de vie est particulièrement nette dans les pays développés. La conséquence en est un vieillissement de la population. Avec l’avancée en âge, on voit apparaître chez certains hommes, des symptômes ressemblant, a minima, à ceux observés en cas d’hypogonadisme. Toutefois, contrairement à l’arrêt brutal des fonctions ovariennes à la ménopause chez la femme, l’altération des fonctions testiculaires avec l’âge n’est que partielle et progressive chez l’homme. Plusieurs études transversales ont démontré une diminution de la testostérone circulante au cours du vieillissement chez l’homme, et cette diminution persiste si les études ne s’adressent qu’à des hommes en bonne santé. Cette diminution de la testostérone avec l’âge a été récemment confirmée par des études longitudinales, le déclin apparaît progressif, débutant tôt, dès la fin de la trentaine avec une décroissance constante pendant toute la vie. Parallèlement à la diminution de la testostérone totale dans le sang, la Sex Hormone Binding Globulin (SHBG) augmente avec l’âge, ainsi, la testostérone libre et la testostérone non liée à la SHBG (appelée testostérone biodisponible) diminuentelles de manière encore plus nette que la testostérone totale avec l’âge. Comme d’autres facteurs de variations de la SHBG sont fréquemment rencontrés chez les sujets âgés, en particulier sa diminution chez l’obèse et/ou en cas d’insulinorésistance, et comme la mesure fiable de la testostérone libre par dialyse à l’équilibre n’est pas réalisable en pratique clinique, la mesure de la testostérone biodisponible représente le meilleur moyen de faire le diagnostic du déficit androgénique partiel du sujet âgé. L’élévation de la LH chez le sujet âgé en bonne santé, la diminution de la réponse de la testostérone à l’injection d’hCG et la réduction du nombre de cellules de Leydig sont autant d’indicateurs de l’origine testiculaire du déficit en testostérone. Toutefois, la fonction gonadotrope est aussi altérée, de manière relative, avec l’avancée en âge. La sensibilité de l’hypothalamo-hypophyse au rétrocontrôle par les stéroïdes sexuels est augmentée, l’amplitude des épisodes sécrétoires pulsatiles de LH est diminuée et la réponse de la LH à l’injection de GnRH est émoussée par rapport au sujet jeune. II en résulte que le dosage de LH n’est pas un index valide pour diagnostic du déficit androgénique partiel du sujet âgé.

Aucune des fonctions androgenodépendantes altérées chez le sujet âgé (libido, érection, sensation de bien-être, masse et force musculaire, masse grasse, masse osseuse, erythropoïèse…), n’est sous le contrôle exclusif des androgènes et aucun symptôme n’est totalement spécifique du déficit androgénique partiel du sujet âgé. Ainsi en pratique, il est nécessaire d’associer à la symptomatologie clinique, la notion de la diminution de la testostérone biodisponible au-dessous d’un seuil indiquant un déficit en androgène, pour mettre en place un traitement androgénique substitutif. La valeur seuil reste l’objet de discussion, la plupart des auteurs considèrent actuellement comme valeur seuil, la valeur inférieure de la normale des hommes de moins de 40 ans.

Abstract

In contrast with the abrupt cessation of ovarian function at menopause in women, alteration of testicular functions in aging males is partial and progressive. Several cross-sectional studies have demonstrated an age-related decrease of testosterone levels in men. This decrease has also been observed when only men in good health are included in such studies. This age-related decline of testosterone levels has been recently confirmed by a longitudinal study including a large number of subjects. The progressive decline begins early, from the late thirties, and continues at a constant rate throughout the subject’s lifetime. Since SHBG increases with age, free testosterone and non-SHBG-bound testosterone (referred to as bioavailable testosterone) decrease more markedly than total testosterone. As variations of SHBG levels (mainly a decrease in obese and/or insulin-resistant subjects) are often encountered in clinical practice and as it is difficult to reliably measure free testosterone, bioavailable testosterone appears to be the better index to diagnose androgen deficiency in the aging male. Elevation of basal LH levels, decrease of hCG-induced testosterone levels and reduction of Leydig cell number demonstrate the testicular origin of hypogonadism. However, gonadotropic function is also relatively altered with aging. As a result of this alteration of gonadotropic function, LH level is not a reliable index of hypogonadism in the aging male.

None of the androgen-dependent functions that are altered with aging, i.e. libido, erectile function, sense of well-being, muscle mass, muscle strength, fat mass, bone mass, etc., are exclusively controlled by androgens. In clinical practice, the indication for androgen replacement therapy must therefore be based on a combination of clinical symptoms and a reduction of bioavailable testosterone below a certain cut-off value, indicating “significant” hypogonadism.

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Correspondence to H. Lejeune.

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Communication au XVIII° Congrès de la Société d’Andrologie de Langue Française, Montpellier, 13–15 décembre 2001.

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Lejeune, H. Déficit Androgénique Lié à l’Age. Androl. 11, 231 (2001). https://doi.org/10.1007/BF03034636

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Mots Clés

  • andropause
  • testostérone
  • biodisponible
  • traitement androgénique substitutif

Key Words

  • andropause
  • bioavailable
  • testosterone
  • androgen replacement therapy
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