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Le déficit androgénique lié à l’âge: du diagnostic biologique au traitement substitutif

Androgen deficiency in aging male (ADAM). From biological evaluation to hormone replacement therapy

Résumé

Le déficit androgénique lié à l’âge (DALA) suscite un intérêt croissant étant donné l’allongement de la vie dans les pays développés et la possibilité d’un traitement substitutif supposé protéger les hommes âgés contre les effets de la carence en testostérone. Plusieurs études épidémiologiques ont établi que les paramètres hormonaux les mieux corrélés avec la densité minérale osseuse, la masse musculaire et la force musculaire étaient le taux de la testostérone libre ou de la testostérone biodisponible, ainsi que le taux de l’estradiol biodisponible, c’est-à-dire non lié à la testostérone-estradiol binding globulin (TeBG). En effet la diminution avec l’âge de la sécrétion testiculaire est masquée par l’augmentation du taux de la TeBG si l’on se contente de mesurer la testostérone totale. Une autre difficulté pour le diagnostic biologique du DALA est l’incertitude quant aux seuils à prendre en considération. Certes, par consensus tacite, la plupart des investigateurs considèrent que sont déficitaires les hommes dont le taux de testostérone biodisponible est au-dessous de la limite inférieure des hommes adultes jeunes, généralement le cinquième percentile. En réalité, cette attitude empirique n’est pas totalement validée scientifiquement, d’autant que l’on ignore tout de l’évolution avec l’âge de la sensibilité des récepteurs androgéniques. Mais cette prise de position permet d’identifier les hommes âgés candidats à un traitement hormonal substitutif. Actuellement plusieurs formulations de testostérone sont disponibles, permettant son administration par voie orale, intra0musculaire, ou transdermique. L’undécanoate de testostérone (Pantestone®) pris par la bouche est en principe transporté par la voie du canal thoracique, court-circuitant partiellement le métabolisme hépatique.

L’énanthate de testostérone (Androtardyl®) et l’heptylate de testostérone (Testostérone Heptylate®) sont des préparations huileuses retards actives 2 ou 3 semaines. Mais les taux obtenus peuvent être supra-physiologiques dans les jours suivant l’injection. Les formulations transdermiques sont d’apparition plus récente. Le dispositif Androderm® est un patch d’application quotidienne, dont la cinétique d’absorption mime le rythme circadien de la testostérone, mais les taux de dihydrotestostérone (DHT) peuvent être supra-physiologiques. La testostérone en gel (Androgel®) produit, par une seule application quotidienne, des taux stables de testostérone, DHT et estradiol. Le choix entre ces différentes formulations dépend des besoins du patient, de ses demandes et de sa compliance pour un mode d’administration donné.

Abstract

There is increasing interest in the assessment of testicular function in aging men, probably because of an increasing number of males above 60 years and because of the emerging gap in the medical management of aging between men and women. In the last three decades, the endocrinological problems of menopause have been thoroughly taken into consideration, while the decline in testis activity in the so called andropause was only recently recognized to deserve a similar interest. In fact, testis endocrine function is not so easy to evaluate in elderly men: total testosterone (tT) level declines very slowly and it is a fallacious index of testis function because of the increase in testosterone/estradiol binding globulin (TeBG) levels in aging males. Free testosterone level is an accurate index when measured by reference techniques, while routine direct assays using testosterone analogues have been proven to be unreliable diagnostic tools. The measurement of bioavailable testosterone (bT) after ammonium sulfate precipitation of TeBG-bound testosterone is currently considered as the method of choice for diagnosing ADAM syndrome. Indeed, in aging males, bT levels are more closely correlated than tT with bone mineral density, muscle strength and muscle mass. Bioavailable estradiol is also a reliable index of testis aging in elderly males and is strongly correlated with bone mineral density. Unfortunately a serious expertise is needed for accurate measurement of bioavailable estradiol levels. Another difficulty in the diagnosis of ADAM syndrome in the uncertainty in the bT threshold to be taken into account. The 5th percentile of bT levels in young adult men can be arbitrarily choosen; however, there is no definite proof that such a threshold is totally appropriate, since no data are available regarding the evolution with years of androgen receptor sensitivity. Nevertheless, identifying androgen deficiency by means of bT measurement may lead to hormone replacement therapy, at least as a therapeutic test. Several formulations of testosterone are currently available using oral, intra-muscular and transdermal routes. Testosterone undecanoate (Pantestone®) is given orally and is supposed to reach the blood stream via the lymph thoracic channel. Intra-muscular testosterone in oil (Androtardyl® and Testosterone Heptylate®) can maintain high testosterone levels for two to three weeks, but can also induce supra-physiological levels of testosterone and dihydrotestosterone (DHT) within the first week after injection. Transdermal formulations have been recently proposed as non-invasive ways to administer testosterone while by-passing liver metabolism. Permeation enhanced transdermal system (Androderm®) can mimic the testosterone circadian rythm, but testosterone levels may be supra-physiological for several hours. DHT levels however are generally maintained whithin physiological values. Testosterone gel (Androgel®) can induce stable and physiological levels of testosterone, DHT and estradiol. Care should be taken to avoid contamination of the familial environment by testosterone after its application. The choice between these formulations depends obviously on the patient’s needs, the patient’s requests, and the patient’s compliance with a particular formulation.

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Roger, M., Lahlou, N. Le déficit androgénique lié à l’âge: du diagnostic biologique au traitement substitutif. Androl. 12, 138 (2002). https://doi.org/10.1007/BF03034960

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Mots-clés

  • Homme
  • vieillissement
  • testostérone biodisponible
  • estradiol biodisponible
  • traitement hormonal substitutif

Key words

  • male
  • aging
  • bioavailable testosterone
  • bioavailable estradiol
  • hormone replacement therapy
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