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Case reports describe persistent erectile dysfunction (PED) associated with exposure to 5α-reductase inhibitors (5α-RIs). Clinical trial reports and the manufacturers' full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5α-RI exposure and that sexual adverse effects of 5α-RIs resolve in men who discontinue exposure. Our chief objective was to assess whether longer duration of 5α-RI exposure increases risk of PED, independent of age and other known risk factors. Men with shorter 5α-RI exposure served as a comparison control group for those with longer exposure. We used a single-group study design and classification tree analysis (CTA) to model PED (lasting ≥90 days after stopping 5α-RI). Covariates included subject attributes, diseases, and drug exposures associated with sexual dysfunction. Our data source was the electronic medical record data repository for Northwestern Medicine. The analysis cohorts comprised all men exposed to finasteride or dutasteride or combination products containing one of these drugs, and the subgroup of men 16-42 years old and exposed to finasteride ≤1.25 mg/day. Our main outcome measure was diagnosis of PED beginning after first 5α-RI exposure, continuing for at least 90 days after stopping 5α-RI, and with contemporaneous treatment with a phosphodiesterase-5 inhibitor (PDE I). Other outcome measures were erectile dysfunction (ED) and low libido. PED was determined by manual review of medical narratives for all subjects with ED. Risk of an adverse effect was expressed as number needed to harm (NNH). Among men with 5α-RI exposure, 167 of 11,909 (1.4%) developed PED (persistence median 1,348 days after stopping 5α-RI, interquartile range (IQR) 631.5-2320.5 days); the multivariable model predicting PED had four variables: prostate disease, duration of 5α-RI exposure, age, and nonsteroidal anti-inflammatory drug (NSAID) use. Of 530 men with new ED, 167 (31.5%) had new PED. Men without prostate disease who combined NSAID use with >208.5 days of 5α-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure (NNH 59.8, all < 0.002). Among men 16-42 years old and exposed to finasteride ≤1.25 mg/day, 34 of 4,284 (0.8%) developed PED (persistence median 1,534 days, IQR 651-2,351 days); the multivariable model predicting PED had one variable: duration of 5α-RI exposure. Of 103 young men with new ED, 34 (33%) had new PED. Young men with >205 days of finasteride exposure had 4.9-fold higher risk of PED (NNH 108.2, < 0.004) than men with shorter exposure. Risk of PED was higher in men with longer exposure to 5α-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors.

Introduction Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Objective The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. Methods This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. Results Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01–3.82); BCC and ARBs (OR 2.86; 95% CI 2.13–3.83), ACEIs (OR 2.23; 95% CI 1.78–2.81) and TZs (OR 2.11; 95% CI 1.60–2.79); SCC and ARBs (OR 2.22; 95% CI 1.37–3.61), ACEIs (OR 1.94; 95% CI 1.37–2.76), and TZs (OR 4.11; 95% CI 2.66–6.35). Conclusions A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

Importance Case reports describe persistent erectile dysfunction (PED) associated with exposure to 5[alpha]-reductase inhibitors (5[alpha]-RIs). Clinical trial reports and the manufacturers' full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5[alpha]-RI exposure and that sexual adverse effects of 5[alpha]-RIs resolve in men who discontinue exposure. Objective Our chief objective was to assess whether longer duration of 5[alpha]-RI exposure increases risk of PED, independent of age and other known risk factors. Men with shorter 5[alpha]-RI exposure served as a comparison control group for those with longer exposure. Design We used a single-group study design and classification tree analysis (CTA) to model PED (lasting [greater than or equal to]90 days after stopping 5[alpha]-RI). Covariates included subject attributes, diseases, and drug exposures associated with sexual dysfunction. Setting Our data source was the electronic medical record data repository for Northwestern Medicine. Subjects The analysis cohorts comprised all men exposed to finasteride or dutasteride or combination products containing one of these drugs, and the subgroup of men 16-42 years old and exposed to finasteride [less than or equal to]1.25 mg/day. Main outcome and measures Our main outcome measure was diagnosis of PED beginning after first 5[alpha]-RI exposure, continuing for at least 90 days after stopping 5[alpha]-RI, and with contemporaneous treatment with a phosphodiesterase-5 inhibitor (PDE.sub.5 I). Other outcome measures were erectile dysfunction (ED) and low libido. PED was determined by manual review of medical narratives for all subjects with ED. Risk of an adverse effect was expressed as number needed to harm (NNH). Results Among men with 5[alpha]-RI exposure, 167 of 11,909 (1.4%) developed PED (persistence median 1,348 days after stopping 5[alpha]-RI, interquartile range (IQR) 631.5-2320.5 days); the multivariable model predicting PED had four variables: prostate disease, duration of 5[alpha]-RI exposure, age, and nonsteroidal anti-inflammatory drug (NSAID) use. Of 530 men with new ED, 167 (31.5%) had new PED. Men without prostate disease who combined NSAID use with >208.5 days of 5[alpha]-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure (NNH 59.8, all p 205 days of finasteride exposure had 4.9-fold higher risk of PED (NNH 108.2, p < 0.004) than men with shorter exposure. Conclusion and relevance Risk of PED was higher in men with longer exposure to 5[alpha]-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors.