Post-finasteride Syndrome Research Articles

A comment on the post-finasteride syndrome

The post-Finasteride syndrome (PFS) has been claimed to occur in men who have taken oral finasteride to treat hair loss or benign prostatic hyperplasia. While the incidence of persistent sexual, mental, and physical side effects despite quitting finasteride is unknown, and the condition is not recognized by the scientific community, individuals who suffer from PFS do present with very distinctive and homogenous symptoms. The concept has emerged from reports of nondermatologists, neuroendocrinological research, case reports, and uncontrolled studies. These have been scrutinized by hair experts who found that persistent sexual side effects were only documented in low-quality studies with a strong bias selection and a significant nocebo effect. Others totally dispute the credibility of the PFS. In any case, the PFS is a problem that has to be dealt with. Low-quality studies neither confirm nor refute the condition as a valid nosologic entity. Therefore, it is as inappropriate to dismiss the condition, as it would be to demonize finasteride for the treatment of male pattern hair loss. Whether the PFS represents a nocebo reaction or a real drug adverse event is irrelevant, while the best way to alleviate the emotional distress related to hair loss is to effectively treat the condition causing the problem. It is not sufficient to only discuss the plausibility of the PFS. There is a need for practical recommendations to include such important issues as patient selection and risk assessment, appropriate patient information, how to react in case of drug-related adverse events, issues of fertility and malignancy, management of the PFS, and alternatives, specifically the use of topical finasteride. It is the aim of this commentary to provide the respective information.

Finasteride as a model for personalized medicine

The side effects of Finasteride are currently a subject of controversy. Some studies report minor or acceptable adverse effects, which decrease after a variable period of time so that they do not necessitate terminating Finasteride administration. However, several clinical and neuro-endocrine studies show that some adverse effects persist indefinitely in the form of post-Finasteride syndrome, even after the drug cessation. This paper presents a possible explanation for these inconsistent findings. First, the study design of either informing or not informing patients prior therapy about possible adverse effects can influence the incidence and magnitude of reported adverse effects. Second, structural and information dichotomies of the brain generate four distinct neuronal networks, which are activated through specific cerebral neuromodulators and that are able to support four distinct minds within an individual body. As a conclusion, the “mind psychophysiology” and the corresponding mental impairments differ across individuals, such that not only the prediction of adverse effects should be addressed from a more individualized medical perspective, but also the therapeutic strategies could be tailored to the four distinct mental profiles described. It is a personalized approach that would be applicable to several interrelated domains of neuroscience, like psychology, psychiatry and sexuality. Finally, this perspective may represent a starting point for a more individualized understanding of mental events, perhaps even a step forward in the understanding of the mind-body problem.

Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients

Recent reports show that, in patients treated with finasteride for male pattern hair loss, persistent side effects including sexual side effects, depression, anxiety and cognitive complaints may occur. We here explored the psychiatric and andrological features of patients affected by post-finasteride syndrome (PFS) and verified whether the cerebrospinal fluid (CSF) and plasma levels of neuroactive steroids (i.e., important regulators of nervous function) are modified. We found that eight out of sixteen PFS male patients considered suffered from a DSM-IV major depressive disorder (MDD). In addition, all PFS patients showed erectile dysfunction (ED); in particular, ten patients showed a severe and six a mild-moderate ED. We also reported abnormal somatosensory evoked potentials of the pudendal nerve in PFS patients with severe ED, the first objective evidence of a neuropathy involving peripheral neurogenic control of erection. Testicular volume by ultrasonography was normal in PFS patients. Data obtained on neuroactive steroid levels also indicate interesting features. Indeed, decreased levels of pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone), dihydrotestosterone and 17beta-estradiol and increased levels of dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol were observed in CSF of PFS patients. Neuroactive steroid levels were also altered in plasma of PFS patients, however these changes did not reflect exactly what occurs in CSF. Finally, finasteride did not only affect, as expected, the levels of 5alpha-reduced metabolites of progesterone and testosterone, but also the further metabolites and precursors suggesting that this drug has broad consequence on neuroactive steroid levels of PFS patients.

Safety Profile of Finasteride: Distribution of Adverse Effects According to Structural and Informational Dichotomies of the Mind/Brain.

Finasteride is currently used extensively for male androgenic alopecia and benign prostatic hyperplasia; however, some adverse effects are severe and even persistent after treatment cessation, the so-called 'post-finasteride syndrome'. The following most severe adverse effects-sexual dysfunction and depression-often occur together and may potentiate one other, a fact that could explain (at least in part) the magnitude and persistence of finasteride adverse effects. This paper presents the pharmacological action of finasteride and the corresponding adverse effects, the biological base explaining the occurrence, persistence and distribution of these adverse effects, and a possible therapeutic solution for post-finasteride syndrome. The distribution of finasteride adverse effects is presented within a comprehensive and modern neuro-endocrine perspective related to structural and informational dichotomies of the brain. Understanding the variation of finasteride side effects among different populations would be necessary not only to delineate the safety profile of finasteride for different subgroups of men (a subject may or may not be affected by a certain anti-hormonal compound dependent on the individual neuro-endocrine profile), but also as a possible premise for a therapeutic approach of finasteride adverse effects. Such therapeutic approach should include administration of exogenous hormones, which are deficient in men with post-finasteride syndrome, namely dihydrotestosterone (in right-handed men) or progesterone/dihydroprogesterone (in left-handed subjects).

Androgen Receptor (AR) Gene (CAG)n and (GGN)n Length Polymorphisms and Symptoms in Young Males With Long-Lasting Adverse Effects After Finasteride Use Against Androgenic Alopecia.

IntroductionLong-term adverse symptoms of men who used oral finasteride against androgenic alopecia have been recently described as post-finasteride syndrome (PFS).AimTo determine whether (CAG)n-rs4045402 and (GGN)n-rs3138869 polymorphisms in the androgen receptor (AR) gene are implicated in PFS.MethodsAR polymorphisms were studied according to PFS symptoms in 66 white participants (31.8% Italian, 28.8% American, and 39.4% other).Main Outcome MeasuresSymptoms were investigated by an ad hoc 100-item questionnaire and the Arizona Sexual Experience Scale and Aging Male Symptom Scale (AMS). (CAG)n and (GGN)n repeats were categorized as short ([CAG]9–19, [GGN]<23), medium ([CAG]20–24, [GGN]23), or long ([CAG]25–37, [GGN]>23).ResultsMedian age was 32 years, duration of finasteride use was 360 days, and time from finasteride discontinuation was 1,053 days. We observed several frequency differences in symptoms according to (CAG)n and (GGN)n repeat numbers. Three AMS items were worse for medium (GGN)23 than for long (GGN)>23 carriers and one item was worse for short (GGN)<23 carriers. The AMS item for decrease in sexual desire or libido was worse for short (CAG)9–19 carriers than for medium (CAG)20–24 carriers. Through the ad hoc questionnaire, significant findings in (CAG)n and/or (GGN)n repeats were obtained for penile discomfort, loss of scrotal sensitivity, scrotal discomfort, less pubic hair, loss of perceived perineal fullness, increased sperm density, involuntary muscle spasms, loss of muscle tone, increased weight (>2 kg), increased skin dryness, and onset of symptoms after finasteride use.ConclusionThis study showed that short and/or long (CAG)n and (GGN)n repeats had different frequencies according to symptoms reported by patients with PFS, likely reflecting the vast array of genes modulated by the AR. This study showed a U-curvilinear profile of (CAG)n repeats for skin dryness symptoms, where the two extremes exhibited a worse condition than medium repeats. Further studies are necessary to investigate the PFS pathophysiology using a precision medicine approach.

004 Post Finasteride Syndrome: Is dutasteride unfairly accused?

Finasteride (FIN), a 5α−reductase inhibitor (5−ARI’s), is used to treat benign prostatic hyperplasia and alopecia. Controversial research has suggested that finasteride, can result in persistent sexual and nonsexual side effects known as post−finasteride syndrome (PFS). Because of a shared mechanism of action, dutasteride voluntarily underwent an FDA label change similar to that for FIN. The aim of this study was to evaluate adverse effects associated with dutasteride by examining an FDA Adverse Event Reporting Symptoms (FAERS) database. The aim of this report was to address PFS putatively induced by dutasteride by quantifying and summarizing these FAERS reports, create a demographic of patient reports, assess the cluster of PFS symptoms, and to correlate consistency of the PFS syndrome. A FAERS database between 4/1/2011 and 10/29/2014 pertaining to all 5−ARI’s received was analyzed. Every reported case was coded according to date received, case type, whether it was reported by a health professional, outcomes, manufacturer, age of patient, country, product used, adverse events, and the suspected role of the reported drug.

Post-finasteride syndrome: newly recognised condition

Post-finasteride syndrome: newly recognised condition

Emotional Consequences of Finasteride: Fool's Gold.

Androgenetic alopecia, the gradual, progressive loss of hair frequently results in psychological despair, in part related to changes in self-image. Current androgenetic alopecia treatments are limited to hair transplantation and medications that inhibit dihydrotestosterone, a potent androgen associated with follicular micronization. Users of finasteride, which prevents dihydrotestosterone production, report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome. Psychiatric illnesses and personality traits, specifically neuroticism influence emotional well-being. Limited research exists exploring the psychological corollaries of post-finasteride syndrome and preexisting Axis I and Axis II mental health conditions. The aim of this study was to explore how having a preexisting personal and/or familial history of a psychiatric diagnosis and certain personality traits may influence anxiety and depression among finasteride users. Participants in this online survey completed the Beck Depression Inventory, the Beck Anxiety Inventory, and Ten-Item Personality Inventory. An important finding in this study was that almost 57% ( n = 97) of men reported a psychiatric diagnosis and 28% ( n = 27) had a first-degree relative with a mental health disorder, of this group 17 only had a family history. Nearly 50% of the men surveyed reported clinically significant depression as evidenced by Beck Depression Inventory score and 34% experienced anxiety on the Beck Anxiety Inventory. There were no statistically significant trends in personality traits reported. Results provide evidence on the need to screen for psychiatric history and counseling patients about the potential psychological consequences of finasteride. Prescribing clinicians should carefully weigh the risk/benefit ratio with these patients.

An observational retrospective evaluation of 79 young men with long-term adverse effects after use of finasteride against androgenetic alopecia.

Concern regarding adverse effects of finasteride is increasing. We aimed to determine the type and frequency of symptoms in men having long-term sexual and non-sexual side effects after finasteride treatment (a condition recently called post-finasteride syndrome, PFS) against androgenetic alopecia (AGA). Subjects were recruited at the Urology Unit of the Trieste University-Hospital, and from a dedicated website. Out of 79 participants, 34% were white Italians, mean age was 33.4 ± 7.60 years, mean duration of finasteride use was 27.3 ± 33.21 months; mean time from finasteride discontinuation was 44.1 ± 34.20 months. Symptoms were investigated by an ad hoc 100 questions' questionnaire, and by validated Arizona Sexual Experience Scale (ASEX) and Aging Male Symptom Scale (AMS) questionnaires. By ASEX questionnaire, 40.5% of participants declared getting and keeping erection very difficult, and 3.8% never achieved; reaching orgasm was declared very difficult by 16.5%, and never achieved by 2.5%. By the ad hoc questionnaire, the most frequent sexual symptoms referred were loss of penis sensitivity (87.3%), decreased ejaculatory force (82.3%), and low penile temperature (78.5%). The most frequent non-sexual symptoms were reduced feeling of life pleasure or emotions (anhedonia) (75.9%); lack of mental concentration (72.2%), and loss of muscle tone/mass (51.9%). We contributed to inform about symptoms of PFS patients; unexpectedly loss of penis sensitivity was more frequent than severe erectile dysfunction and loss of muscle tone/mass was affecting half of the subjects. Further studies are necessary to investigate the pathophysiological and biochemical pathways leading to the post-finasteride syndrome.

Post-Finasteride Syndrome: About 2 Cases and Review of the Literature

Introduction: Finasteride is widely used in the treatment of benign prostatic hyperplasia and androgenetic alopecia. Persistent sexual adverse events in patients that withdraw the drug was poorly studied. Materials and methods: case report study of two clinical cases of post-finasteride syndrome. Case 1: 27 year old male who, after 7 months of finasteride 1mg/day intake for androgenetic alopecia, began with erectile dysfunction, low libido, hypospermia, muscular hipotrophy and penile shrinking, in a persistent and progressive way although withdrawal of the drug. He was also evaluated by a psychiatrist. Case 2: 23 year old male that after the intake of 1 pill of finasteride 1mg for androgenetic alopecia began with erectile dysfunction, low libido, hypospermia, less intense orgasms, asthenia, muscle pain and penile shrinking, in a persistent and progressive way although withdrawal of the drug. He is under psychiatric evaluation. Results: Case 1: Hormonal profiles were normal, with a dihydrotestosterone of 192 pg/ml and the penile ultrasound showed an hyperechogenicity at the distal portion of the right corpus cavernosum. The genetic determination of the CAG triplets of the androgen receptor gene showed a value of 24 repetitions. Treatment with Tadalafil and vacuum therapy was effective, although not complete, but he didn't benefit from the 3 month application of Andractim®, with a posterior benefit from the application of HCG 6000 UI/week associated with Anastrozole 2mg/week, with normal hormonal controls. Case 2: penile Doppler and hormonal profiles were normal. Treatment with Tadalafil was effective, although not complete. There was no adherence to other treatments. Conclusion: post-finasteride syndrome is a little known entity with an unknown physiopathology, and is currently under study. Awareness should be promoted about the existence of this syndrome in order to give the best assistance to these patients until we have a better comprehension of this entity.

Co-editors’ Messages

1. Mario Marzola, MBBS (editors{at}ISHRS.org) 1. Adelaide, South Australia </br>![][1]</img> Dear readers, I am very concerned with the increasing discussion and publicity given to post finasteride syndrome (PFS). It is gaining a momentum of its own, receiving prominence in the media and

Post-Finasteride Syndrome (PFS) Update: Point/Counterpoint

1. Edwin S. Epstein, MD, FISHRS (esehairmd{at}gmail.com) 1. Richmond, Virginia, USA At the ISHRS 2015 Annual Scientific Meeting in Chicago, we heard an update on the constellation of symptoms that has come to be known as Post-Finasteride Syndrome (PFS). The update was presented by guest

A pharmacogenetic survey of androgen receptor (CAG)n and (GGN)n polymorphisms in patients experiencing long term side effects after finasteride discontinuation.

Finasteride is a steroid 5-alpha-reductase inhibitor, approved for the treatment of androgenetic alopecia (AGA) and benign prostate hyperplasia. In some patients the treatment is associated with adverse side effects that could become persistent after therapy discontinuation, resulting in the so-called post-finasteride syndrome (PFS). A pharmacogenetic component in the response to finasteride treatment was previously demonstrated. Two polymorphisms (CAG) rs4045402 and (GGN) rs3138869 in the gene encoding for the androgen receptor (AR) have been hypothesized to play a role in finasteride sensitivity. We aimed to compare the rs4045402 and rs3138869 polymorphisms prevalence in a group of 69 selected subjects (AGA+PFS) that used finasteride to treat alopecia and developed persistent side effects, with that in a group of 91 untreated subjects with AGA (AGA), and a group of 76 untreated subjects without AGA (NO-AGA). The rs4045402 and rs3138869 polymorphisms extreme-lengths alleles were more frequent among AGA+PFS (odds ratio, 5.88; 95% CI, 1.87-18.52) and AGA subjects (odds ratio, 3.55; 95% CI, 1.13-11.21) than among NO-AGA subjects, probably reflecting the genetic predisposing factors for AGA development. In conclusion, we described a predictive effect of the less common repeats' length CAG-rs4045402 and GGN-rs3138869 on AGA development. Prospective trials are required to confirm our findings also in other ethnicities, and to highlight possible further pharmacogenetic predictive markers of susceptibility to adverse effects.

Persistent sexual, emotional, and cognitive impairment post-finasteride: a survey of men reporting symptoms.

Finasteride is a synthetic 5-α reductase inhibitor, which prevents the conversion of testosterone to dihydrotestosterone and has been used for more than 20 years in the treatment of male pattern hair loss. Randomized, controlled trials have associated finasteride with both reversible and persistent adverse effects. In this pilot study, we sought to characterize sexual and nonsexual adverse effects that men reported experiencing at least 3 months after stopping the medication. Based on previous research on persistent side effects of finasteride, we constructed an Internet survey targeting six domains: physical symptoms, sexual libido, ejaculatory disorders, disorders of the penis and testes, cognitive symptoms, and psychological symptoms and was e-mailed to patients who reported experiencing symptoms of side effects of finasteride. Responses from 131 generally healthy men (mean age, 24 years) who had taken finasteride for male pattern hair loss was included in the analysis. The most notable finding was that adverse effects persisted in each of the domains, indicating the possible presence of a "post-finasteride syndrome."