RESUMO
Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through "Darwinian" treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.
RESUMO
BACKGROUND AND AIM: One of the main causes of mortality among obese patients is cardiovascular disease (CVD). Carotid intima-media thickness (CIMT) is an independent predictor for atherosclerosis and risk of CVD, and has been demonstrated to be related with obesity. This study aimed to evaluate the effect of substantial weight loss after bariatric surgery on CIMT. METHODS: This prospective study was performed on patients with morbid obesity and standard indications for bariatric surgery in a tertiary referral center in Iran. The mean CIMT values were assessed using B-mode ultrasonography before and 6 months after bariatric surgery. RESULTS: A total of 32 patients (25 females, 7 males) with a mean age of 38.18 ± 1.18 years were enrolled. Body mass index (BMI) was significantly reduced from 43.66 ± 6.44 to 29.01 ± 2.56 kg/m2 during 6 months following surgery (p: 0.001). The mean CIMT values at 6 months after surgery were significantly lower than the baseline (0.53 ± 0.06 vs. 0.50 ± 0.08; p: 0.001). Along with a significant hypertension and metabolic syndrome remission, we observed considerable reduction in FBS (p: 0.019), cholesterol (p: 0.061), triglycerides (p: 0.001), and insulin levels (p: 0.001). Besides, liver stiffness was significantly decreased after surgery (6.15 ± 0.82 vs. 5.26 ± 0.83; p: 0.001). There was no statistically significant correlation between changes in quantitative variables and changes in CIMT. CONCLUSION: Bariatric surgery results in significant reduction in CIMT, metabolic syndrome factors, and liver stiffness in patients with morbid obesity.
