Post-finasteride syndrome
Post-finasteride syndrome is a type of long term or permanent adverse effects, mainly sexual and erectile dyfunction, following the use of finasteride or dutasteride, medications used for the treatment of androgenic alopecia (AGA) and benign prostatic hyperplasia (BPH).[1][2] Despite the growing number of reports concerning the occurrence of symptoms subsequent to treatment with these medications, the condition is still not officially recognized as a separate medical condition (rather as side effects linked to finasteride that persist after discontinuation)[3][4][5] and it's mechanism is not fully understood.[6] The people reporting persistent sexual dysfunction after finasteride have normal levels of sex hormones, markers of peripheral androgen action no different than in healthy men, although the difference has been found in brain fmri, with findings indicating "abnormal function in brain circuitry linked to sexual arousal and major depression".[7] The research completed in 2016 did not find an evidence of altered AR-dependent gene expression in penile skin[7], although in another research conducted in 2021 the significat changes in gene expression in penile skin has been identified, with "1,446 genes significantly over-expressed and 2,318 genes significantly under-expressed in study patients".[8] Moreover, the increased levels of androgen receptors (AR) have been found in genital tissues of young people affected by the syndrome.[9] The condition seems similar to post-SSRI sexual dysfunction as both involve sexual dysfunction long persisting after discontinuation of the drug and both are not well understood,[10] although the relationship seems rather superficial, that is symptomatic.
Possible mechanisms
As mentioned before, the etiology of these cases is unclear. The 5 alpha-reductase inhibitors (finasteride and dutasteride) are able to pass the blood brain barrier where type I and II of this enzyme are present and not only hinder the conversion of testosteron to dihydrotestosteron but also "the reduction of progesterone to 5α-dihydroprogesterone and of deoxycorticosterone to 5α-dihydrodeoxycorticosterone, associated with higher levels T, DHEA and 3alfa-diol as was reported in the CSF of PFS patients in comparison with those observed in healthy patients".[11][12] The finasteride can possibly induce changes in the neurosteroid metabolism in the central nervous system as well as the expression of their receptors and cause decrease in the neurogenesis of the hippocampus in the male mice, with the latter present also in depression.[13][14]
The other proposition states that due to ubiquitous nature of the alpha-reductase and important role played by dihydrotestosterone[15], the androgen deficiency can lead to yet not fully understood changes in the same way that DHT deficit blocks the growth of prostate, causes liver problems (fat buildup, fibrosis) and dry eye disease as well as impaired sperm production.[12]
The research also found gut dysregulation, that is changes to microbiota and gut inflammation (increased levels of pro-inflammatory cytokines like IL-1β and TNF-α, as well as serotonin) in male rates following the finasteride withdrawal, that given the importance of gut-brain axis, can contribute to development of sexual and psychological symptoms of the disorder.[16]
Symptoms
Apart from sexual and erectile dysfunction, some people report other adverse reactions, like depression, anxiety, suicidal ideation[17], memory impairment,[18] muscle weakness, penile shrinkage and numbness[9] or insomnia among others.[19] In the years 2011-2021 the FDA has received over 700 reports of suicide and suicidal thoughts among finasteride users (at least 100 deaths) and 34 such reports (10 deaths) in the years 1997-2011.[20]
Management
Currently, there are no official or scientifically based guidelines as to management or treatment of the PFS.[12]
References
- ↑ Diviccaro, Silvia; Melcangi, Roberto Cosimo; Giatti, Silvia (May 1, 2020). "Post-finasteride syndrome: An emerging clinical problem". Neurobiology of Stress. 12. doi:10.1016/j.ynstr.2019.100209. PMC 7231981 Check
|pmc=value (help). PMID 32435662 Check|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ Cilio, Simone; Tsampoukas, Georgios; Morgado, Afonso; Ramos, Pedro; Minhas, Suks (June 23, 2025). "Post-finasteride syndrome - a true clinical entity?". International Journal of Impotence Research. 37 (6): 426–435. doi:10.1038/s41443-025-01025-6. PMID 39953145 Check
|pmid=value (help) – via www.nature.com. - ↑ "Actualité - Finastéride : rappel sur les risques de troubles psychiatriques et de la fonction sexuelle". ANSM.
- ↑ "Finasteride: reminder of the risk psychiatric side effects and of sexual side effects (which may persist after discontinuation of treatment)". GOV.UK.
- ↑ https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020788s030lbl.pdf | page 5 [bare URL PDF]
- ↑ Traish, Abdulmaged M. (January 1, 2020). "Post-finasteride syndrome: a surmountable challenge for clinicians". Fertility and Sterility. 113 (1): 21–50. doi:10.1016/j.fertnstert.2019.11.030. PMID 32033719 Check
|pmid=value (help) – via www.fertstert.org. - ↑ 7.0 7.1 Basaria, Shehzad; Jasuja, Ravi; Huang, Grace; Wharton, Whitney; Pan, Hong; Pencina, Karol; Li, Zhuoying; Travison, Thomas G.; Bhawan, Jag; Gonthier, Renaud; Labrie, Fernand; Dury, Alain Y.; Serra, Carlo; Papazian, Allen; o'Leary, Michael; Amr, Sami; Storer, Thomas W.; Stern, Emily; Bhasin, Shalender (2016). "Characteristics of Men Who Report Persistent Sexual Symptoms After Finasteride Use for Hair Loss". The Journal of Clinical Endocrinology & Metabolism. 101 (12): 4669–4680. doi:10.1210/jc.2016-2726. PMC 5155688. PMID 27662439.
- ↑ Howell, Skyler; Song, Weitao; Pastuszak, Alexander; Khera, Mohit (2021). "Differential Gene Expression in Post-Finasteride Syndrome Patients". The Journal of Sexual Medicine. 18 (9): 1479–1490. doi:10.1016/j.jsxm.2021.05.009. PMID 34247957 Check
|pmid=value (help). - ↑ 9.0 9.1 Di Loreto, Carla; La Marra, Francesco; Mazzon, Giorgio; Belgrano, Emanuele; Trombetta, Carlo; Cauci, Sabina (2014). "Immunohistochemical evaluation of androgen receptor and nerve structure density in human prepuce from patients with persistent sexual side effects after finasteride use for androgenetic alopecia". PLOS ONE. 9 (6): e100237. Bibcode:2014PLoSO...9j0237D. doi:10.1371/journal.pone.0100237. PMC 4069023. PMID 24959691.
- ↑ Giatti, Silvia; Diviccaro, Silvia; Cioffi, Lucia; Cosimo Melcangi, Roberto (January 1, 2024). "Post-Finasteride Syndrome And Post-Ssri Sexual Dysfunction: Two Clinical Conditions Apparently Distant, But Very Close". Frontiers in Neuroendocrinology. 72. doi:10.1016/j.yfrne.2023.101114. PMID 37993021 Check
|pmid=value (help) – via ScienceDirect. Unknown parameter|article-number=ignored (help) - ↑ Melcangi, Roberto Cosimo; Santi, Daniele; Spezzano, Roberto; Grimoldi, Maria; Tabacchi, Tommaso; Fusco, Maria Letizia; Diviccaro, Silvia; Giatti, Silvia; Carrà, Giuseppe; Caruso, Donatella; Simoni, Manuela; Cavaletti, Guido (July 1, 2017). "Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients". The Journal of Steroid Biochemistry and Molecular Biology. 171: 229–235. doi:10.1016/j.jsbmb.2017.04.003. hdl:11380/1131597. PMID 28408350 – via ScienceDirect.
- ↑ 12.0 12.1 12.2 Leliefeld, Herman H. J.; Debruyne, Frans M. J.; Reisman, Yakov (June 23, 2025). "The post-finasteride syndrome: possible etiological mechanisms and symptoms". International Journal of Impotence Research. 37 (6): 414–421. doi:10.1038/s41443-023-00759-5. PMID 37697052 Check
|pmid=value (help) – via www.nature.com. - ↑ Hercher, Christa; Turecki, Gustavo; Mechawar, Naguib (July 1, 2009). "Through the looking glass: Examining neuroanatomical evidence for cellular alterations in major depression". Journal of Psychiatric Research. 43 (11): 947–961. doi:10.1016/j.jpsychires.2009.01.006. PMID 19233384 – via ScienceDirect.
- ↑ Giatti, S.; Cioffi, L.; Diviccaro, S.; Piazza, R.; Melcangi, R. C. (October 1, 2024). "Analysis of the finasteride treatment and its withdrawal in the rat hypothalamus and hippocampus at whole-transcriptome level". Journal of Endocrinological Investigation. 47 (10): 2565–2574. doi:10.1007/s40618-024-02345-y. PMC 11393021 Check
|pmc=value (help). PMID 38493246 Check|pmid=value (help) – via Springer Link. - ↑ Azzouni, Faris; Godoy, Alejandro; Li, Yun; Mohler, James (August 23, 2012). "The 5 Alpha-Reductase Isozyme Family: A Review of Basic Biology and Their Role in Human Diseases". Advances in Urology. 2012 (1): 530121. doi:10.1155/2012/530121. PMC 3253436. PMID 22235201.
- ↑ Diviccaro, Silvia; Giatti, Silvia; Cioffi, Lucia; Falvo, Eva; Herian, Monika; Caruso, Donatella; Melcangi, Roberto Cosimo (2022). "Exploration of the Possible Relationships Between Gut and Hypothalamic Inflammation and Allopregnanolone: Preclinical Findings in a Post-Finasteride Rat Model". Biomolecules. 12 (11). doi:10.3390/biom12111567. PMC 9687671 Check
|pmc=value (help). PMID 36358917 Check|pmid=value (help). - ↑ "Measures to minimise risk of suicidal thoughts with finasteride and dutasteride medicines | European Medicines Agency (EMA)". www.ema.europa.eu. May 8, 2025.
- ↑ Zhang, Hao; Ou, Hongqi; Zhao, Panli; Luo, Xi; Zhang, Ping; Huang, Hua (June 13, 2025). "Association between finasteride with subjective memory deficits: a study from the NHANES and FAERS databases". Frontiers in Neurology. 16. doi:10.3389/fneur.2025.1616851. PMC 12202497 Check
|pmc=value (help). PMID 40584531 Check|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ "About Post-Finasteride Syndrome – The Post-Finasteride Syndrome Foundation".
- ↑ Levine, Dan; Terhune, Chad (4 February 2021). "Exclusive: Merck anti-baldness drug Propecia has long trail of suicide reports, records show". Reuters.
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