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An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87-0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81-0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa.

Aim: The aim of this systematic review was to assess the effects on psychosocial and mental health, cognition, body composition, and metabolic markers of hormone treatment in children with gender dysphoria. Methods: Systematic review essentially follows PRISMA. We searched PubMed, EMBASE and thirteen other databases until 9 November 2021 for English-language studies of hormone therapy in children with gender dysphoria. Of 9934 potential studies identified with abstracts reviewed, 195 were assessed in full text, and 24 were relevant. Results: In 21 studies, adolescents were given gonadotropin-releasing hormone analogues (GnRHa) treatment. In three studies, cross-sex hormone treatment (CSHT) was given without previous GnRHa treatment. No randomised controlled trials were identified. The few longitudinal observational studies were hampered by small numbers and high attrition rates. Hence, the long-term effects of hormone therapy on psychosocial health could not be evaluated. Concerning bone health, GnRHa treatment delays bone maturation and bone mineral density gain, which, however, was found to partially recover during CSHT when studied at age 22 years. Conclusion: Evidence to assess the effects of hormone treatment on the above fields in children with gender dysphoria is insufficient. To improve future research, we present the GENDHOR checklist, a checklist for studies in gender dysphoria.

Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3–6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4–6.7) for PSA > 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0–5.5). Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH.

IMPORTANCE Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD. OBJECTIVE To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016. EXPOSURES Treatment with GnRH agonists and PCa diagnosis were the primary exposures. MAIN OUTCOMES AND MEASURES Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association. RESULTS The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.

Objectives The objective of this study is to find clinical variables that predict the prognosis for men with castration-resistant prostate cancer (CRPC) in a Swedish real-life CRPC cohort, including a risk group classification to clarify the risk of succumbing to prostate cancer. This is a natural history cohort representing the premodern drug era before the introduction of novel hormonal drug therapies. Methods PSA tests from the clinical chemistry laboratories serving health care in six regions of Sweden were retrieved and cross-linked to the National Prostate Cancer Registry (NPCR) to identify men with a prostate cancer diagnosis. Through further cross-linking with data sources at the Swedish Board of Health and Welfare, we retrieved other relevant information such as prescribed drugs, hospitalizations, and cause of death. Men entered the CRPC cohort at the first date of doubling of their PSA nadir value with the last value being >2 ng/ml, or an absolute increase of >5 ng/ml or more, whilst on 3 months of medical castration or if they had been surgically castrated (n = 4098). By combining the two variables with the largest C-statistics, “PSA at time of CRPC” and “PSA doubling time,” a risk group classification was created. Rsults PSA-DT and PSA at date of CRPC are the strongest variables associated with PC specific survival. At the end of follow-up, the proportion of men who died due to PC was 57%, 71%, 81%, 86%, and 89% for risk categories one through five, respectively. The median overall survival in our cohort of men with CRPC was 1.86 years (95% CI: 1.79–1.97). Conclusion For a man with castration-resistant prostate cancer, there is a high probability that this will be the main cause contributing to his death. However, there is a significant difference in mortality that varies in relation to tumor burden assessed as PSA doubling time and PSA at time of CRCP. This information could be used in a clinical setting when deciding when to treat more or less ag