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Risques prostatiques de la testostérone : nouveau retour du balancier?

Risks of testosterone for prostate: new pendulum swing back?

Résumé

Depuis les années 1940, la testostérone (T) est réputée dangereuse pour la prostate, bien que sans preuve solide. Les études longitudinales ne montrent pas de corrélation entre taux de T et incidence des cancers de la prostate (CaP), dont les formes graves sont au contraire associées à des taux faibles de cette hormone. Les essais cliniques randomisés contre placebo de traitement par la T n’ont pas montré d’augmentation de l’incidence du CaP dans les groupes T. Ces données rassurantes ont conduit certains à prescrire des traitements de substitution androgénique à des hommes porteurs de néoplasies intra-épithéliales prostatiques, ou précédemment traités pour un CaP de bon pronostic, ou sous surveillance active pour un tel cancer non traité, sans qu’apparaisse un risque élevé de progression ou de récidive du CaP sous ce traitement. Il ne fait pourtant aucun doute que la prostate normale et son cancer, au moins dans ses formes évoluées, sont faits de tissus androgénodépendants. Ces apparentes contradictions pourraient s’expliquer, outre par la possibilité d’une très faible diffusion de la T circulante dans le tissu prostatique, par l’hypothèse d’une saturation des récepteurs androgéniques prostatiques dès des niveaux très bas de T circulante, proches des taux de castration, expliquant qu’une augmentation de la T au-delà de ce niveau ne puisse pas stimuler le tissu prostatique. Quelques publications récentes d’évolution de CaP sous traitement androgénique, persistant parfois à l’arrêt de ce traitement, montrent qu’on ne peut pas généraliser les résultats très favorables des études précédentes. Des données objectives suggèrent aussi que le niveau de saturation du récepteur androgénique prostatique pourrait être en réalité proche de la limite inférieure des taux physiologiques de T. Il faut donc rester prudent avant d’élargir les indications du traitement par la T chez les hommes avec antécédent de CaP. Seules des études randomisées à grande échelle, en double insu contre placebo, permettront de se faire une idée exacte des risques auxquels expose ce traitement.

Abstract

Since the 1940’s, testosterone (T) is deemed dangerous to the prostate, though without solid evidence. Longitudinal studies do not show association between T levels and prostate cancer (PCa) incidence. To the contrary, aggressive PCa cases are associated with low T levels. Randomized placebo controlled trials of T therapy do not show any increase in PCa incidence in the T groups. These reassuring data have led some doctors to prescribe T replacement therapy to men with prostatic intraepithelial neoplasia, or previously treated for a low grade PCa, or under active surveillance for such untreated cancer without showing a high risk of progression or recurrence of cancer with this treatment. There is however no doubt that normal prostate and PCa, at least in its advanced forms, are made with androgen-dependent tissues. These apparent contradictions might be explained, besides the possibility of a very low diffusion of circulating T in the prostate, by the hypothesis of a saturation of the prostate androgen receptors from very low levels of circulating T, close to castration levels, explaining that an increase in T beyond this level cannot stimulate the prostate tissue. Some recent reports of PCa progression under T therapy, sometimes persisting despite T withdrawal, show that the reassuring results of the previous studies cannot be generalized. Objective data also suggest that the saturation level of the prostate androgen receptor is actually close to the lower limit of the normal T range. We must remain cautious about expanding the indication of T therapy in men with a history of PCa. Only large-scale, randomized, double-blind placebo controlled trials, will provide reliable information on the prostatic risks of such a treatment.

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Author information

Correspondence to J. Buvat.

Additional information

Centre d’Études et de Traitement de l’Appareil Reproducteur et de la Psychosomatique (CETPARP)

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Mots clés

  • Testostérone
  • Androgénothérapie
  • Cancer de la prostate
  • Néoplasie intra-épithéliale prostatique
  • Revue de la littérature

Keywords

  • Testosterone
  • Androgen therapy
  • Prostate cancer
  • Prostatic intraepithelial neoplasia
  • Literature review