Kiguradze Tina, Temps William H, Yarnold Paul R, Cashy John, Brannigan Robert E, Nardone Beatrice, Micali Giuseppe, West Dennis Paul, Belknap Steven M
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Optimal Data Analysis LLC, San Diego, CA, USA.
PeerJ. 2017 Mar 9;5:e3020. doi: 10.7717/peerj.3020. eCollection 2017.
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 (PDEI). 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.
病例报告描述了与接触5α还原酶抑制剂（5α-RIs）相关的持续性勃起功能障碍（PED）。非那雄胺和度他雄胺的临床试验报告及制造商完整处方信息（FPI）指出，延长5α-RI暴露时间不会增加性不良反应风险，且5α-RIs的性不良反应在停止暴露的男性中会消退。
我们的主要目标是评估延长5α-RI暴露时间是否会增加PED风险，而不受年龄和其他已知风险因素的影响。5α-RI暴露时间较短的男性作为暴露时间较长男性的对照比较组。
我们采用单组研究设计和分类树分析（CTA）对PED（停止5α-RI后持续≥90天）进行建模。协变量包括与性功能障碍相关的受试者属性、疾病和药物暴露情况。
我们的数据来源是西北医学的电子病历数据库。
分析队列包括所有接触过非那雄胺、度他雄胺或含有其中一种药物的复方产品的男性，以及16至42岁且每天接触非那雄胺≤1.25mg的男性亚组。
我们的主要结局指标是首次5α-RI暴露后开始诊断为PED，在停止5α-RI后持续至少90天，并同时使用磷酸二酯酶-5抑制剂（PDEI）进行治疗。其他结局指标是勃起功能障碍（ED）和性欲减退。通过人工查阅所有患有ED的受试者的医疗记录来确定PED。不良反应风险用伤害所需人数（NNH）表示。
在接触5α-RI的男性中，11909人中有167人（1.4%）发生了PED（停止5α-RI后持续时间中位数为1348天，四分位间距（IQR）为631.5 - 2320.5天）；预测PED的多变量模型有四个变量：前列腺疾病、5α-RI暴露时间、年龄和非甾体抗炎药（NSAID）的使用。在530名新发ED的男性中，167人（31.5%）患有新发PED。未患前列腺疾病且同时使用NSAID且5α-RI暴露时间>208.5天的男性发生PED的风险比暴露时间较短的男性高4.8倍（NNH为59.8，P均<0.002）。在16至42岁且每天接触非那雄胺≤1.25mg的男性中，4284人中有34人（0.8%）发生了PED（持续时间中位数为1534天，IQR为651 - 2351天）；预测PED的多变量模型有一个变量：5α-RI暴露时间。在103名新发ED的年轻男性中，34人（33%）患有新发PED。非那雄胺暴露时间>205天的年轻男性发生PED的风险比暴露时间较短的男性高4.9倍（NNH为108.2，P<0.004）。
5α-RI暴露时间较长的男性发生PED的风险更高。在年轻男性中，较长时间接触非那雄胺导致PED的风险比所有其他评估的风险因素都更大。
