Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study

Melcangi, Roberto Cosimo; Casarini, Livio; Marino, Marco; Santi, Daniele; Sperduti, Samantha; Giatti, Silvia; Diviccaro, Silvia; Grimoldi, Maria Grazia; Caruso, Donatella; Cavaletti, Guido; Simoni, Manuela

doi:10.1530/ec-19-0199

Cited by 10 publications

(7 citation statements)

References 64 publications

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“…Several studies (69,73,74,127,149) reported that depressive symptoms were significantly more prevalent in finasteride users than in non-users and the incidence of moderate to severe depressive symptoms were higher in the finasteride treated patients than in non-users. Suicidal thoughts were declared in 44% of the former finasteride users and only in 3% of the controls (62,69,73,74,75). An analysis of the FDA database (FEARS) revealed persistent suicidal ideation in 7.9% of males (127).…”

Section: Debruyne Et Al 2004 (106)mentioning

confidence: 98%

Post-finasteride syndrome: a surmountable challenge for clinicians

Traish

2020

Fertility and Sterility

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Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities. (Fertil Steril Ò 2020;113:21-50. Ó2019 by American Society for Reproductive Medicine.

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Section: Debruyne Et Al 2004 (106)mentioning

confidence: 98%

Post-finasteride syndrome: a surmountable challenge for clinicians

Traish

2020

Fertility and Sterility

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“…There is some evidence for penile curvature or other penile effects in men with PFS [ 25 ], but it is not clear if this was present prior to treatment or has resulted since. Alterations in neuroactive steroid levels [ 34 ], methylation of 5 alpha-reductase type 2 in cerebrospinal fluid [ 35 ], and gut microbiota population [ 36 ] have also been found in PFS patients. But again, it is not clear whether these were present before treatment.…”

Section: Post-finasteride Syndrome (Pfs)mentioning

confidence: 99%

Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin

Healy

Bahrick

Bak

et al. 2022

JRS

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BACKGROUND: A set of enduring conditions have been reported in the literature involving persistent sexual dysfunction after discontinuation of serotonin reuptake inhibiting antidepressants, 5 alpha-reductase inhibitors and isotretinoin. OBJECTIVE: To develop diagnostic criteria for post-SSRI sexual dysfunction (PSSD), persistent genital arousal disorder (PGAD) following serotonin reuptake inhibitors, post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction (PRSD). METHODS: The original draft was designed using data from two published case series (Hogan et al., 2014 and Healy et al., 2018), which represent the largest public collections of data on these enduring conditions. It was further developed with the involvement of a multidisciplinary panel of experts. RESULTS: A set of criteria were agreed upon for each of the above conditions. Features of PSSD, PFS and PRSD commonly include decreased genital and orgasmic sensation, decreased sexual desire and erectile dysfunction. Ancillary non-sexual symptoms vary depending on the specific condition but can include emotional blunting and cognitive impairment. PGAD presents with an almost mirror image of unwanted sensations of genital arousal or irritability in the absence of sexual desire. A new term, post-SSRI asexuality, is introduced to describe a dampening of sexual interest and pleasure resulting from a pre-natal or pre-teen exposure to a serotonin reuptake inhibitor. CONCLUSIONS: These criteria will help in both clinical and research settings. As with all criteria, they will likely need modification in the light of developments.

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“…On the other hand, it is important to highlight that observations obtained in PFS patients and in male rats after finasteride suspension show the nervous system as an important target, with alterations that could be associated with sexual dysfunction, such as depressive symptomatology and peripheral neuropathy. 7,20,27,28,32,45 In addition, it is important to remember that male sexual behavior (e.g., sexual motivation and reward to sexual performance) is under the control of complex neural circuits. 1,52 Therefore, future experiments will be important to explore whether finasteride withdrawal affects these circuits and molecules involved, such as neurotransmitters and neuropeptides.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 Interestingly, these side effects may persist after the drug suspension, inducing the so-called post-finasteride syndrome (PFS). 9,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] The effects of finasteride treatment were also reported in animal models. For instance, finasteride treatment in castrated rats decreased erectile response, although receiving T replacement 35,36 and in control male rats, it decreased intracavernosal pressure during electrical stimulation of cavernous nerves.…”

Section: Introductionmentioning

confidence: 97%

Exploring rat corpus cavernosum alterations induced by finasteride treatment and withdrawal

Diviccaro,

Herian,

Cioffi

et al. 2023

Andrology

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Despite its efficacy for treating androgenetic alopecia, finasteride, an inhibitor of 5α‐reductase (i.e., the enzyme converting testosterone, T, into dihydrotestosterone, DHT), is associated with several side effects including sexual dysfunction (e.g., erectile dysfunction). These side effects may persist after drug suspension, inducing the so‐called post‐finasteride syndrome (PFS). The effects of subchronic treatment with finasteride (i.e., 20 days) and its withdrawal (i.e., 1 month) in rat corpus cavernosum have been explored here. Data obtained show that the treatment was able to decrease the levels of the enzyme 5α‐reductase type II in the rat corpus cavernosum with increased T and decreased DHT levels. This local change in T metabolism was linked to mechanisms associated with erectile dysfunction. Indeed, by targeted metabolomics, we reported a decrease in the nitric oxide synthase (NOS) activity, measured by the citrulline/arginine ratio and confirmed by the decrease in NO2 levels, and a decrease in ornithine transcarbamylase (OTC) activity, measured by citrulline/ornithine ratio. Interestingly, the T levels are negatively correlated with NOS activity, while those of DHT are positively correlated with OTC activity. Finasteride treatment also induced alterations in the levels of other molecules involved in the control of penile erection, such as norepinephrine and its metabolite, epinephrine. Indeed, plasma levels of norepinephrine and epinephrine were significantly increased and decreased, respectively, suggesting an impairment of these mediators. Interestingly, these modifications were restored by suspension of the drug. Altogether, the results reported here indicate that finasteride treatment, but not its withdrawal, affects T metabolism in the rat corpus cavernosum, and this alteration was linked to mechanisms associated with erectile dysfunction. Data here reported could also suggest that the PFS sexual side effects are more related to dysfunction in a sexual central control rather than peripheral compromised condition.

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Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study

Cited by 10 publications

References 64 publications

Post-finasteride syndrome: a surmountable challenge for clinicians

Post-finasteride syndrome: a surmountable challenge for clinicians

Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin

Exploring rat corpus cavernosum alterations induced by finasteride treatment and withdrawal

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