ADT and the metabolic syndrome: no good deed goes unpunished
Notice bibliographique
Résumé
Although androgen deprivation therapy (ADT) has been used for more than half a century to treat prostate cancer, its mechanism and associated side effects are continuously updated. Androgens are key players in glucose homeostasis and lipid metabolism. In fact, lower total testosterone predicts a higher incidence of the metabolic syndrome, a cluster of risk factors predisposing patients to late onset diabetes mellitus, atherosclerosis and cardiovascular (CVS) morbidity and mortality.1 Since CVS disease is the most common competing cause for mortality, we should make all efforts to minimize our iatrogenic contribution to the metabolic syndrome and familiarize ourselves with the growing body of evidence linking ADT to the metabolic syndrome.2,3 Mohamedali and colleagues present their experience with the impact of long-term ADT on blood glucose levels in non-diabetic prostate cancer patients. The authors demonstrated that 1 year of ADT use is associated with elevated fasting glucose levels.4 This data is in line with a recent review of the ADT/metabolic syndrome which showed a clear casual association between ADT and diabetes mellitus, but the causal association is not as strong with CVS morbidity.5 The link needs to be better explored as novel ADT strategies are about to change our practice. In recent years it has become clear that current modes of castration are far from optimal in achieving complete androgen deprivation in prostate cancer cells. Multiple pre-clinical evidences suggest that prostate cancer cells can produce androgens which activate the androgen receptor already in concentrations lower than those traditionally defined as castrated serum testosterone levels (<20 ng/dL). Accordingly, although not completely validated, clinical observations suggest the lower the testosterone level under ADT, the longer the survival;6 it is possible that even lower levels of testosterone within and it is possible that even transient events of testosterone break through within the framework of ADT can accelerate disease progression.7 Hence, the current trend in ADT is a more strict deprivation of androgens in castrate resistant prostate cancer, and what we used to define as maximal androgen blocked (MAB) will certainly be expanded with the introduction of novel products, such as arbiraterone and MDV3100. It is reasonable to expect that novel therapeutic strategies that induce more effective testosterone suppression will reciprocally accentuate the metabolic side effect profile of ADT. Data comparing the long-term metabolic side effect of different modes of castration is currently limited,8 but once available, should better guide us in treating patients with known risk factors for CVS disease. We should incorporate routine baseline and follow-up assessments of metabolic measurements (fasting glucose levels, lipids, BMI) and advocate lifestyle modification for our ADT patients. We should also stay tuned for potentially more detrimental metabolic side effects with more strict MAB regimens.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,006 | 0,016 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,002 | 0,001 |
| Études des sciences et des technologies | 0,002 | 0,007 |
| Communication savante | 0,005 | 0,013 |
| Science ouverte | 0,002 | 0,004 |
| Intégrité de la recherche | 0,011 | 0,024 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,013 | 0,005 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».