Androgen Deprivation Therapy in Prostate Cancer and Metabolic Risk for Atherosclerosis

Shahani, Sadeka; Braga‐Basaria, Milena; Basaria, Shehzad

doi:10.1210/jc.2007-2595

Cited by 168 publications

(135 citation statements)

References 38 publications

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“…Il est aussi de mise en cas de récidive biologique, locale ou métastatique, et de contre-indication du traitement local à un stade localisé 1 . L'HAA réduit les niveaux sériques de la testostérone, qui passent d'un taux normal d'environ 500 à 600 ng/dl (17,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)8 nmol) à un taux de castration. Classiquement, la castration est considérée comme efficace si le taux de testostérone a été abaissé à un seuil de 50 ng/dl (soit 1,73 nmol/l) ou à une valeur inférieure à 5 % du taux normal 2,3 .…”

Section: Introductionunclassified

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Complications de l’hormonothérapie anti-androgénique du cancer de la prostate

Ziouziou

Karmouni²,

Khader³

et al. 2014

CUAJ

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RésuméLes effets indésirables de l'hormonothérapie anti-androgénique (HAA) dans le traitement du cancer de la prostate sont attribuables à la carence d'androgènes. L'HAA entraîne le syndrome de castration, qui se caractérise par une diminution de la libido, la dysfonction érectile, l'asthénie, des bouffées de chaleur, la diminution des capacités intellectuelles et la dépression. Il en résulte égale-ment une augmentation de la graisse abdominale, ce qui favorise l'insulinorésistance et le diabète. La perte de la densité minérale osseuse secondaire à l'HAA entraîne un risque fracturaire accru. Il existe de plus un risque cardiovasculaire important dû aux facteurs métaboliques. L'effet thérapeutique de l'HAA doit donc être soupesé en regard de la toxicité liée à l'hypogonadisme.

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Section: Introductionunclassified

“…La prescription de l'HAA a nettement augmenté aux États-Unis, où le tiers des deux millions de patients ayant un cancer de la prostate reçoivent ce traitement 4 . On assiste également à une forte augmentation de l'utilisation de l'HAA pour traiter les formes localisées de cancer de la prostate 5 .…”

Section: Introductionunclassified

Complications de l’hormonothérapie anti-androgénique du cancer de la prostate

Ziouziou

Karmouni²,

Khader³

et al. 2014

CUAJ

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“…While the role of testosterone and other androgens in CVD risk in men is controversial [49,50], recent clinical, epidemiological, cellular and animal studies have demonstrated that similar to the protective effects of E2 in women, androgens can also have positive effects on the vasculature [25,31,34,51,52]. This is exemplified by the increased incidence of CV risk factors in men with hypogonadism or undergoing androgen deprivation therapy (ADT) as part of their treatment regimen for prostate cancer [28][29][30]. Mechanistically, androgens have been implicated in several cardioprotective processes including in preventing vascular remodelling and promoting re-endothelialisation, where reduced proliferation of vascular smooth muscle cells and increased growth of endothelial cells is observed in response to DHT [53].…”

Section: Discussionmentioning

confidence: 99%

“…including in men with hypogonadism and in men undergoing androgen deprivation therapy (ADT) as part of their treatment for prostate cancer [28][29][30]. Consistent with this, a 5 year study in elderly men showed that high serum testosterone was associated with a decreased risk of cardiovascular incidents [31].…”

Section: Introductionmentioning

confidence: 94%

Regulated expression of the prostacyclin receptor (IP) gene by androgens within the vasculature: Combined role for androgens and serum cholesterol

Eivers

Kinsella

2016

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The prostanoid prostacyclin plays a key cardioprotective role within the vasculature. There is increasing evidence that androgens may also confer cardioprotection but through unknown mechanisms. This study investigated whether the androgen dihydrotestosterone (DHT) may regulate expression of the prostacyclin/I prostanoid receptor or, in short, the IP in platelet-progenitor megakaryoblastic and vascular endothelial cells. DHT significantly increased IP mRNA and protein expression, IP-induced cAMP generation and promoter (PrmIP)-directed gene expression in all cell types examined. The androgen-responsive region was localized to a cis-acting androgen response element (ARE), which lies in close proximity to a functional sterol response element (SRE) within the core promoter. In normal serum conditions, DHT increased IP expression through classic androgen receptor (AR) binding to the functional ARE within the PrmIP. However, under conditions of low-cholesterol, DHT led to further increases in IP expression through an indirect mechanism involving AR-dependent upregulation of SCAP expression and enhanced SREBP1 processing & binding to the SRE within the PrmIP. Chromatin immunoprecipitation assays confirmed DHTinduced AR binding to the ARE in vivo in cells cultured in normal serum while, in conditions of low cholesterol, DHT led to increased AR and SREBP1 binding to the functional ARE and SRE cis-acting elements, respectively, within the core PrmIP resulting in further increases in IP expression. Collectively, these data establish that the human IP gene is under the transcriptional regulation of DHT, where this regulation is further influenced by serum-cholesterol levels. This may explain, in part, some of the protective actions of androgens within the vasculature. Acknowledgements:We thank Dr Helen M. Reid for reading the manuscript during its preparation.

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“…2,3 In patients with distant metastases, ADT improves quality of life. 4,5 Although ADT is beneficial in these patient populations, it is often used as primary therapy in men with localized disease and in men encountering biochemical recurrence 6 without evidence of survival advantage. The overall use of ADT has increased in the past two decades 7 and its use in men with localized disease and biochemical recurrence accounts a great deal for this increase.…”

Section: Introductionmentioning

confidence: 99%

Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications

Collins¹,

Basaria²

2012

Asian J Androl

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Prostate cancer (PCa) is the most common malignancy in men. Prostate being an androgen responsive tissue, androgen deprivation therapy (ADT) is used in the management of locally advanced (improves survival) and metastatic (improves pain and quality of life) PCa. Over the past two decades, the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences, though without any evidence of survival advantage. Hypogonadism resulting from ADT is associated with decreased muscle mass and strength, increased fat mass, sexual dysfunction, vasomotor symptoms, decreased quality of life, anemia and bone loss. Insulin resistance, diabetes and cardiovascular disease have recently been added to the list of these complications. As the majority of men with PCa die of conditions other than their primary malignancy, recognition and management of these adverse effects is paramount. Here we review data evaluating metabolic and cardiovascular complications of ADT.

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Androgen Deprivation Therapy in Prostate Cancer and Metabolic Risk for Atherosclerosis

Cited by 168 publications

References 38 publications

Complications de l’hormonothérapie anti-androgénique du cancer de la prostate

Complications de l’hormonothérapie anti-androgénique du cancer de la prostate

Regulated expression of the prostacyclin receptor (IP) gene by androgens within the vasculature: Combined role for androgens and serum cholesterol

Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications

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