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Déficit androgénique lié à l’âge. Que faut-il attendre de l’androgénothérapie?

What results can be expected from androgen replacement therapy in age-related androgen deficiency?

Resume

En dehors de tout contexte pathologique ou de prise médicamenteuse, la sénéscence s’accompagne de plusieurs modifications de l’équilibre androgénique. Le taux de production de testostérone s’abaisse avec,a contrario, augmentation de sa capacité de liaison aux protéines porteuses. La fraction libre de la testostérone, considérée comme la seule biologiquement active, s’abaisse, aboutissant, lorsque ce phénomène dépasse un certain seuil, à une hypo-androgénie tissulaire. Le tableau clinique qui en est la conséquence emprunte plus ou moins profondément les symptômes de l’hypogonadisme masculin: asthénie physique et psychique, réduction de la libido et des capacités érectiles, inflation de la masse adipeuse aux dépends de la masse maigre, gynécomastie, ostéoporose et altérations métaboliques pro-athéromateuses.

La définition du seuil de testostéronémie au dessous duquel la responsabilité d’un déficit androgénique peut être retenue devant un tableau clinique compatible représente une question clef dont dépendra l’attitude thérapeutique. Faute de référence clairement validée dans une population d’hommes âgés en bonne santé, le seuil considéré comme pathologique a été fixé à la moyenne du taux plasmatique de testostérone des hommes de 30 à 50 ans diminuée de deux déviations standard, rejoignant ainsi la zone de l’hypogonadisme de l’homme adulte. L’association de signes cliniques évocateurs et d’un abaissement de la testostérone totale ou mieux biodisponible, amène à proposer une androgénothérapie substitutive, une fois les contre-indications (notamment prostatiques) écartées.

L’objectif de la thérapeutique est de lutter contre les conséquences de l’hypo-testostéronémie, stigmate biologique du déficit androgénique associé à l’avancée en âge. Certains bénéfices sont manifestes et clairement démontrés comme la réduction de la masse grasse, le gain de masse maigre et de force musculaire. Il en est de même de la minéralisation osseuse qui s’accroît d’autant plus que le taux de testostérone initial est bas. Il est en effet essentiel de souligner que ces effets bénéfiques sont observés chez des hommes âgés authentiquement hypogonadiques, ce qui,a contrario, n’est pas démontré chez l’homme âgé non déficitaire en testostérone.

A l’inverse de la substitution par la testostérone qui peut en favoriser le développement, le recours à un traitement par dihydrotestostérone aura un effet réducteur sur la gynécomastie. Enfin, lorsque l’hypogonadisme participe à la genèse de troubles de la sexualité, la substitution androgénique s’avèrera efficace si les autres facteurs de causalité, susceptibles d’intervenir conjointement à l’hypogonadisme, sont également traités. L’androgénothérapie substitutive améliore le bien-être et l’asthénie physique de l’homme hypogonadique. Rien de tel n’est cependant démontré chez l’homme dont le seul critère de sélection est l’âge. Si l’androgénothérapie substitutive d’un hypogonadisme n’exerce pas d’influence délétère sur les paramètres lipidiques, ses éventuels effets protecteurs vasculaires restent à démontrer.

En conclusion, la substitution androgénique, prescrite dans le strict respect de ses contre-indications, apportera des effets bénéfiques quel que soit l’âge, à condition que l’hypogonadisme soit clairement établi. Elle n’apporte par contre aucun bénéfice symptomatique démontré dans les autres cadres pathologiques.

Abstract

With the exception of disease or drug-induced changes in Leydig cell function, aging is accompanied by specific changes of androgen status in healthy men. The level of testosterone production decreases in contrast with the rise in plasma protein testosterone binding capacity. Free testosterone, considered to be the biologically active fraction, decreases, leading to tissue androgen deficiency. The resulting clinical picture mimics hypogonadism, including physical and psychological asthenia, decreased libido and sexual behaviour, increased fat mass and decreased lean mass, gynaecomastia, osteoporosis and pro-atherogenic metabolic changes.

The cut-off value for plasma testosterone below which androgen deficiency can be considered to be responsible for clinical signs is a key point which determines the therapeutic approach. In the absence of clearly validated data in healthy aging males, this cut-off value has been consensually defined as the mean plasma testosterone levels of men between 30 and 50 years of age minus two standard deviations, corresponding to the zone of hypogonadism in adult males. The association of clinical signs compatible with hypogonadism and reduced total (or preferably bioavailable) plasma testosterone level justifies initiation of hormone replacement therapy after excluding any contraindications (especially prostatic).

The aim of this treatment is to reverse the consequences of age-related hypogonadism. Some benefits of this treatment have been clearly demonstrated, such as a decrease of fat mass, and an increase of lean mass and muscle strength. Similarly, bone mineral density increases, particularly in men with the lowest pretreatment plasma testosterone levels. It must be stressed that these changes are observed in truly hypogonadal aging men, but not in aging men with normal plasma testosterone levels.

Testosterone replacement therapy can promote the development of gynaecomastia, while dihydrotestosterone tends to reduce gynaecomastia.

Finally, androgen replacement therapy appears to improve a hypogonadism-related decrease in libido or sexual behaviour, provided other associated non-endocrine factors have been previously treated. Androgen replacement therapy improves well-being, and physical and psychological asthenia in hypogonadal men. However, this treatment has not been demonstrated to be effective in healthy aging men. Although androgen replacement therapy does not have a negative impact on lipid parameters, its possible cardiovascular protective effects have not yet been demonstrated.

In conclusion, androgen replacement therapy, respecting the contraindications, is beneficial in patients of all ages with clearly demonstrated hypogonadism, but has no efficacy on symptoms in other cases.

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Correspondence to Jean Marc Kuhn.

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Communication au XXo Congrès de la Société d’Andrologie de Langue Française, Orléans, 11–13 décembre 2003.

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Kuhn, J.M., Thorin-Savouré, A. Déficit androgénique lié à l’âge. Que faut-il attendre de l’androgénothérapie?. Androl. 14, 267 (2004). https://doi.org/10.1007/BF03034914

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Mots clés

  • sénéscence
  • déficit androgénique
  • hypogonadisme masculin

Key words

  • aging
  • partial androgen deficiency
  • male hypogonadism