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Background: The constellation of persistent sexual, neurological, and physical adverse effects in patients who discontinue 5α-reductase inhibitors (5ARIs) has garnered recent concern. The objective of this study was to evaluate potential penile vascular changes and persistent adverse effects of 5ARIs in men treated for androgenic alopecia (AGA).Methods: This was a prospective case-control study with 25 subjects with a history of 5ARI use for AGA and 28 controls. Patient self-reported questionnaires including the International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), Patient Health Questionnaire-9 (PHQ-9), the Epworth Sleepiness Scale (ESS) and the Androgen Deficiency in the Aging Male (ADAM) were used. Penile duplex Doppler ultrasound (PDDU) results were evaluated in men with a history of 5ARI use.Results: A significant difference in total IIEF score between the 5ARI (median: 35; IQR: 29-43) and control group (median: 29; IQR: 27-32) (P=0.035) was observed. Seventeen 5ARI subjects (68%) had a vascular abnormality on PDDU. The median (IQR) for total IPSS score for the 5ARI group was 10 [5-16] compared to 3 [2-8] for the controls (P<0.01). The 5ARI group had a higher median total PHQ-9 score than controls [10 (6.5-16) vs. 1 (0-2) (P<0.001)]. Two subjects (8%) committed suicide during or after the study.Conclusions: While the sexual side effects of 5ARIs are well known, there may be persistent genitourinary, physical, psycho-cognitive, anti-androgenic and penile vascular changes after 5ARI discontinuation. Use of 5ARIs for treatment of AGA may lead to persistent sexual, genitourinary, physical, psycho-cognitive, and anti-androgenic sequelae even after cessation of 5ARI therapy.

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