Androgen Receptor Roles in Insulin Resistance and Obesity in Males: The Linkage of Androgen-Deprivation Therapy to Metabolic Syndrome

Yu, I‐Chen; Lin, Hung-Yun; Sparks, Janet D.; Yeh, Shuyuan; Chang, Chawnshang

doi:10.2337/db13-1505

Cited by 62 publications

(46 citation statements)

References 118 publications

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“…However, there are scarce and ambiguous data regarding the implications of metabolic abnormalities in the prognosis and response to novel hormonal therapies for CRPC patients (Halabi et al 2007, Conteduca et al 2015. Those conclusions would be of particular importance since androgen deprivation therapy (ADT) has been shown to induce insulin resistance (Yu et al 2014).…”

Section: :9mentioning

confidence: 99%

Uncontrolled diabetes predicts poor response to novel antiandrogens

Karantanos¹,

Karanika²,

Gignac³

2016

Endocrine-Related Cancer

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Metabolic abnormalities including hyperglycemia and hyperlipidemia have been associated with worse prognosis of prostate cancer (PCa), but there are limited data regarding their impact on the prognosis of castrate-resistant prostate cancer (CRPC) and the response of novel antiandrogens, namely abiraterone acetate (AA) and enzalutamide. Retrospective analysis of 61 patients with CRPC on AA or enzalutamide, treated at the Boston Medical Center, was performed. We evaluated hemoglobin A1c (HbA1c), HDL, LDL, Triglycerides and BMI within 2 months before the initiation of treatment with AA or enzalutamide and progression-free survival (PFS) under this treatment. Regression analysis and analysis of variance were used to evaluate the data. HbA1c levels were found to predict adversely the PFS on the novel agents (df (1, 37), P = 0.00, R 2 = 0.40, coeff = −3.28). The Kaplan-Meier analysis showed that there is significant difference in survival between the HbA1c 4.7-5.9% compared with patients with HbA1c 7.8-11.6% (6.72 ± 1.3 months, log rank test P < 0.0001) LDL (P = 0.07), HDL (P = 0.14), and triglycerides (P = 0.33) were not found to predict PFS. BMI predicted PFS positively (df (1.59), P = 0.02, R 2 = 0.09, coeff = 0.03), but not independently of HbA1c (P = 0.07). No significant implications of social and family history, previous chemotherapy regimen, and Gleason score with PFS were found. Multiple markers of patients' health state were not associated with HbA1c values. Uncontrolled diabetes can predict for poor response of CRPC patients to AA and enzalutamide determining PFS under this treatment. Elevated BMI can positively affect PFS at this stage of disease.

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Section: :9mentioning

confidence: 99%

Uncontrolled diabetes predicts poor response to novel antiandrogens

Karantanos¹,

Karanika²,

Gignac³

2016

Endocrine-Related Cancer

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“…Testosterone, a major androgen in males, is synthesized in the testes and released into the blood stream, where it binds to steroid hormone-binding globulin [13]. Androgen promotes the growth of lean mass and suppresses fat deposition [13,14]. Low levels of testosterone and steroid hormone-binding globulin may lead to insulin resistance, increased intra-abdominal fat and central obesity [13].…”

Section: Adt and Metabolic Syndromementioning

confidence: 99%

“…Increasingly, ADT with gonadotropin-releasing hormone (GnRH) agonists and antagonists is used to treat nonmetastatic or recurrent disease after definitive treatment [11,12], and is used along with radiation therapy (RT) to treat high-risk, newly diagnosed disease. Testosterone, a major androgen in males, is synthesized in the testes and released into the blood stream, where it binds to steroid hormone-binding globulin [13]. Androgen promotes the growth of lean mass and suppresses fat deposition [13,14].…”

Section: Adt and Metabolic Syndromementioning

confidence: 99%

Metabolic Syndrome in Prostate Cancer: Impact on Risk and Outcomes

2016

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Androgen-deprivation therapy (ADT) is a fundamental element of treatment for nonlocalized prostate cancer and for patients with high-risk disease who are not candidates for radical treatment. ADT has been linked to metabolic syndrome, which involves changes in metabolic factors. While distinct from classic metabolic syndrome, this type does include changes in body composition, lipid profiles and insulin resistance. The constellation of risk factors may be associated with cardiovascular morbidity and the onset of diabetes mellitus. Physicians should discuss in detail the risk and benefits of ADT, as well as any needed lifestyle modifications with patients before beginning therapy.

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“…ADT treatment is associated with more metabolic diseases, atherosclerosis, coronary artery disease, and cardiovascular events [42][43][44][45]. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events.…”

Section: Androgen-deprivation Therapy Late-onset Hypogonadism (Loh) mentioning

confidence: 99%

The biological and clinical advances of androgen receptor function in age-related diseases and cancer [Review]

Takayama

2017

Endocr J

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Abstract. Hormonal alterations with aging contribute to the pathogenesis of several diseases. Androgens mediate their effects predominantly through binding to the androgen receptor (AR), a member of the ligand-dependent nuclear receptor superfamily. By androgen treatment, AR is recruited to specific genomic loci dependent on tissue specific pioneer factors to regulate target gene expression. Recent studies have revealed the epigenetic modulation by AR-associated histone modifiers and the roles of non-coding RNAs in AR signaling. Androgens are male sex hormone to induce differentiation of the male reproductive system required for the establishment of adult sexual function. As shown by several reports using AR knockout mouse models, androgens also have anabolic functions in several tissues such as bone, muscle and central nervous systems. Notably, AR has a central role in prostate cancer progression. Prostate cancer is the most frequently diagnosed cancer in men. Androgen-deprivation therapy for cancer patients and decline of serum androgen with aging promote several diseases associated with aging and quality of life of older men such as osteoporosis, sarcopenia and dementia. Thus, androgen replacement therapy for treating late onset hypogonadism (LOH) or new epigenetic regulators have the potential to overcome the symptoms caused by the low androgen, although adverse effects for cardiovascular diseases have been reported. Given the increasing longevity and consequent rise of age-related diseases and prostate cancer patients, a more understanding of the AR actions in male health remains a high research priority.

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Androgen Receptor Roles in Insulin Resistance and Obesity in Males: The Linkage of Androgen-Deprivation Therapy to Metabolic Syndrome

Cited by 62 publications

References 118 publications

Uncontrolled diabetes predicts poor response to novel antiandrogens

Uncontrolled diabetes predicts poor response to novel antiandrogens

Metabolic Syndrome in Prostate Cancer: Impact on Risk and Outcomes

The biological and clinical advances of androgen receptor function in age-related diseases and cancer [Review]

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