Background: Prostate cancer is a prevalent disease that urgently needs to address its treatment-related complications. By examining existing evidence on the association between Androgen Deprivation Therapy (ADT) and dementia, this study contributes to the understanding of potential risks. We sought to analyze the currently available evidence regarding the risk of dementia, Alzheimer's disease (AD), vascular dementia, and Parkinson's disease (PD) in patients undergoing ADT. Methods: A systematic search of PubMed, EMBASE, Scopus, and Google Scholar was performed to identify studies published from the databases’ inception to April 2023. Studies were identified through systematic review to facilitate comparisons between studies with and without some degree of controls for biases affecting distinctions between ADT receivers and non-ADT receivers. This review identified 305 studies, with 28 meeting the inclusion criteria. Heterogeneity was assessed using Higgins I2%. Variables with an I2 over 50% were considered heterogeneous and analyzed using a Random-Effects model. Otherwise, a Fixed-Effects model was employed. Results: A total of 28 studies were included for analysis. Out of these, only 1 study did not report the number of patients. From the remaining 27 studies, there were a total of 2,543,483 patients, including 900,994 with prostate cancer who received ADT, 1,262,905 with prostate cancer who did not receive ADT, and 334,682 patients without prostate cancer who did not receive ADT. This analysis revealed significantly increased Hazard Ratios (HR) of 1.20 [1.11, 1.29], p < 0.00001 for dementia, HR 1.26 [1.10, 1.43], p = 0.0007 for Alzheimer's Disease, HR 1.66 [1.40, 1.97], p < 0.00001 for depression, and HR 1.57 [1.31, 1.88], p < 0.00001 for Parkinson's Disease. The risk of vascular dementia was HR 1.30 [0.97, 1.73], p < 0.00001. Conclusion: Based on the analysis of the currently available evidence, it suggests that ADT significantly increases the risk of dementia, AD, PD, and depression.

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potential etiological factor in non-obstructive azoospermic patients. By modeling such mutations in Phf7 knockout mice, we show that the genetic defects are directly responsible for male infertility that prevent histone-to-protamine exchange as previously reported. More importantly, the deficiency of spermatogenesis caused by the deletion of Phf7 through ERV-mediated activation of the immune pathway is a common mechanism of infertility. Moreover, PPARa is an emerging target of immunity and inflammation in testis which ERV suppressed, we further demonstrate that Astaxanthin is a promising drug for treating male infertility. CONCLUSIONS: Our findings identify Phf7 as a target in human infertility and reveal its role as an epigenetic reader, while the loss of Phf7 lead to immune pathways activation which can be rescued by PPARa agonist Astaxanthin.

Hypogonadism was defined as a tT<300 ng/dL, or a documented diagnosis.RESULTS: A total of 36 men were included with a mean age was 58.2 years old (SD 10.4). The mean pre-treatment tT was 459.2 ng/ dL (SD 144.0), and 14 (39.9%) were hypogonadal, of whom 5 (35.7%) were receiving hormonal replacement therapy, 4 on testosterone and 1 on clomiphene. Mean pre-treatment curvature was 47.6 (SD 14.2) and mean post-treatment curvature was 27.8 (SD 10.7), for a mean improvement of 19.9 (40.1%) after a median of 4 cycles (2-8). Hypogonadism was significantly associated with more severe curvature, 54.6 among hypogonadal men compared to 43.2 among eugonadal men (p[0.03); however, baseline curvature and tT were not significantly associated (b[-0.03; R 2 [0.09; p[0.08). On linear regression analysis, tT did not significantly predict improvement in degrees (b[-0.02; R 2 [0.06; p[0.14) (Figure 1) or percent (b[0.0; R 2 [0.05; p[0.18). Improvement in neither degrees nor percent differed by hypogonadal status (p[0.14 and p[0.69, respectively). Number of cycles did significantly predict greater improvement in curvature on both univariate and multivariate analyses (b[5.7; R 2 [0.34; p<0.01).CONCLUSIONS: While hypogonadism is associated with more severe curvature, neither total testosterone nor hypogonadism is associated with degree of improvement after CCh treatment. Men should be offered CCh therapy according to guidelines independent of gonadal status.