Roshan Dongre

Background: Male Pattern Baldness (MPB), also known as androgenic alopecia (AGA), is the most common form of hair loss in men and affects an estimated 50 million men and 30 million women the United States.¹ By age 35, 2/3 of American men will have some degree of hair loss and by 50 approximately 85% of men will have significantly thinning hair.¹ 5AR inhibitors such as finasteride and dutasteride have been shown to have great efficacy in stopping this hair loss, but there has become increasing concern of post-finasteride-syndrome (PFS), a phenomenon where side effects like sexual dysfunction and neurological damage persist long-term after cessation of 5AR treatment.²

Methods: A database search in PubMed was performed for relationships among the keywords “finasteride”, “dutasteride”, “post-finasteride syndrome”, and “5-alpha-reductase”. There was also an exclusion criterion of studies published more than five years prior to this review.

Results: Numerous studies explored 5AR inhibitor treatment effects and post-finasteride syndrome mechanisms. In a randomized control trial, 32 patients were compared to controls; both finasteride and dutasteride induced hepatic insulin resistance and lipid accumulation.³ Due to their lipophilic nature, these drugs can traverse the blood-brain barrier, potentially causing epigenetic changes in predisposed individuals.³ In another study, 25 subjects on finasteride for a median of 18 months were compared to controls, revealing significant differences in intercourse satisfaction and penile length loss, although 18 of these subjects had a prior depression history.⁴ Long-term large-sample trials present a more favorable outlook on 5AR treatment. A study tracking 166 AGA patients over 5 years showed no side effects persisting beyond 3 months, with significant hair growth.⁵ Additionally, a study on men over 50 using finasteride found increased suicide/self-harm risk only in those with mood disorder history.⁶ Finally, a 10-year study on 523 Japanese men showed high hair loss efficacy and mild adverse effects, with all patients continuing finasteride throughout the study period.⁷

Conclusions: Androgenic alopecia significantly impacts males, causing stress and anxiety, especially in younger populations. Despite controversy surrounding 5AR inhibitors, conclusive evidence of commonplace long-term side effects directly linked to treatment is lacking. While epigenetic changes are plausible, further research is necessary to mitigate confounding factors.

Works Cited:

1. Lolli F, Pallotti F, Rossi A, et al. Androgenetic alopecia: a review. Endocrine. 2017;57(1):9-17. doi:10.1007/s12020-017-1280-y
2. Traish AM. Post-finasteride syndrome: a surmountable challenge for clinicians. Fertil Steril. 2020;113(1):21-50. doi:10.1016/j.fertnstert.2019.11.030
3. Leliefeld HHJ, Debruyne FMJ, Reisman Y. The post-finasteride syndrome: possible etiological mechanisms and symptoms. Int J Impot Res. Published online September 11, 2023. doi:10.1038/s41443-023-00759-5
4. Khera M, Than JK, Anaissie J, et al. Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia. Transl Androl Urol. 2020;9(3):1201-1209. doi:10.21037/tau.2020.03.21
5. Shin JW, Chung EH, Kim MB, Kim TO, Kim WI, Huh CH. Evaluation of long-term efficacy of finasteride in Korean men with androgenetic alopecia using the basic and specific classification system. J Dermatol. 2019;46(2):139-143. doi:10.1111/1346-8138.14719
6. Laanani M, Weill A, Jollant F, Zureik M, Dray-Spira R. Suicidal risk associated with finasteride versus dutasteride among men treated for benign prostatic hyperplasia: nationwide cohort study. Sci Rep. 2023;13(1):5308. doi:10.1038/s41598-023-32356-3
7. Yanagisawa M, Fujimaki H, Takeda A, Nemoto M, Sugimoto T, Sato A. Long-term (10-year) efficacy of finasteride in 523 Japanese men with androgenetic alopecia. Clin Res Trial. 2019;5(5). doi:10.15761/CRT.1000273