Sexual dysfunction is a feature shared by PFS and PSSD. This common aspect could be casual or rather be determined by common mechanisms that, once detected, could be useful to understand the pathophysiology and to possibly design therapeutic strategies for these conditions. In particular…neuroactive steroids, serotonin and dopamine are variably interconnected with PSSD and PFS… The ﬁnding that both PFS and PSSD, and consequently the persistent sexual dysfunction observed, occurred only in a limited number of patients may suggest possible epigenetic mechanisms.
The levels of some neuroactive steroids analysed in CSF of PFS patients were significantly different versus those in healthy controls. In particular, the levels of PREG, as well as of its further metabolites, PROG and DHP, were significantly decreased in CSF of PFS patients… PFS patients show altered levels of important physiological regulators of brain function, such as neuroactive steroids. This could explain the andrological and psychiatric features observed in PFS patients.
Our chief objective was to assess whether longer duration of 5α-RI exposure increases risk of [persistent erectile dysfunction], independent of age and other known risk factors… Among men with 5α-RI exposure, 167 of 11,909 (1.4%) developed PED… Of 530 men with new ED, 167 (31.5%) had new PED. Men without prostate disease who combined NSAID use with >208.5 days of 5α-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure… Of 103 young men with new ED, 34 (33%) had new PED. Young men with >205 days of finasteride exposure had 4.9-fold higher risk of PED (NNH 108.2, p < 0.004) than men with shorter exposure. Conclusion and relevance: Risk of PED was higher in men with longer exposure to 5α-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors.
Symptomatic finasteride users had “significantly lower International Index of Erectile Function composite score” and “significantly lower scores for each of its domains of erectile function, sexual desire, orgasmic function, intercourse satisfaction, and overall satisfaction”… There exists “a significant positive correlation between a subset of Beck Depression Inventory scores related to negative attitude and blood oxygen level dependent activity in the right nucleus accumbens, left pregenual anterior cingulate cortex, right insula, right lateral orbito-frontal cortex, and left posterior cingulate, as well as a negative correlation between BDI subscores and BOLD activity in the right parahippocampal/ fusiform gyrus. This neural circuitry overlaps with functional abnormalities that have been identified in major depression.”
Recent evidence has shown that [finasteride], albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia. In rat models of these conditions, FIN has been shown to block the effects of dopamine receptors in the nucleusaccumbens (NAcc), a key terminal of the dopamine mesolimbic system. The biological underpinnings of these effects, however, remain mostly elusive… [O]ur results showed that FIN treatment affected the expression of a number of accumbal proteins involved in key functional processes, such as regulation of GABAergic neurotransmission, as well as steroid and pyrimidine metabolism. These findings may prove crucial to understanding the neurochemical mechanisms of FIN’s neuropsychiatric side effects, as well as its potential therapeutic properties for neurological and mental disorders.
Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents.
— Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know? Abdulmaged M. Traish, PhD, Prof. of Biochemistry and Urology, Boston University School of Medicine, Reviews in Endocrine and Metabolic Disorders, Sept. 16, 2015.
Users of finasteride…report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome… Limited research exists exploring the psychological corollaries of post-finasteride syndrome and preexisting Axis I and Axis II mental health conditions… 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.
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)… Out of 79 participants… 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%)…Further studies are necessary to investigate the pathophysiological and biochemical pathways leading to the post-finasteride syndrome.
— An observational retrospective evaluation of 79 young men with long-term adverse effects after use of finasteride against androgenetic alopecia. Carlo Trombetta, MD, Urological Hospital, Departmentof Medical, Surgical and Health Sciences, University of Trieste, January 2016.
Conclusions: The data available in the contemporary literature on the adverse side effects of 5α-RIs do not conclusively suggest that these agents are safe to use in various subsets of patients. If the claimed safety profile indeed exists, then why there are so many patients treated with 5α-RIs seeking medical treatment for restoring their sexual function or recovery from their depression? Thus, the assertion that these drugs are well tolerated and safe is only in the eye of the beholder, and it is warranted to carefully reexamine the impact of the potential adverse effects of these agents not only on sexual function and psychological well-being, but also on other health concerns such as diabetes, bone metabolism, vascular disease, dementia, and cerebrovascular disease. Physicians bear the responsibility to give serious consideration to these adverse and sometimes debilitating and persistent side effects on patient health and discuss the potential adverse effects of these agents with their patients prior to commencing therapy.
— The Impact of the 5α-Reductase Inhibitors (5α-RIs) on Male
Sexual Function and Psychological Well-Being. Abdulmaged M. Traish, Department of Biochemistry, Boston University School of Medicine, August 2015.
Overview of Sexual Dysfunction (SD) and Suicidal Ideation (SI) Reports: A total of 15,518 adverse event reports were submitted [to the FDA] for low-dose finasteride between 1998 and 2013, corresponding to 4910 reports submitted for men aged 18–45 years. Persistent SD and SI adverse events accounted for 11.8% (577 reports) and 7.9% (39 reports), respectively, of the reports submitted for young men using low-dose finasteride. Approximately 87% (34/39 men) who had experienced SI had also reported SD. Conclusion: Our study suggests that young men receiving low-dose finasteride as treatment for androgenic alopecia are at risk of persistent SD, and this risk might contribute to SI.
— Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low-Dose Finasteride: A Pharmacovigilance Study. Ayad K. Ali, Global Patient Safety, Eli Lilly and Company. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, June 1, 2015.
Recent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5α-androstane-3α,17β-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation.
— Safety Concerns Regarding 5α Reductase Inhibitors for the Treatment of Androgenetic Alopecia. Michael S. Irwig, Center for Andrology and Division of Endocrinology, The George Washington University, Washington, D.C.
Conclusions: This study showed that long-term 5α-RIs therapy but not tamsulosin in men with BPH is associated with continued worsening of ED, which does not resolve with continue treatment, contrary to previous claims. Most importantly, it appears that 5α-RIs therapy but not tamsulosin results in reduction of T levels and increased AMS score as well as AST and ALT in liver. These findings raise a safety concern regarding 5α-RI therapy for the long-term. Clinicians are urged to discuss the impact of 5α-RIs therapy with their patients before commencing this therapy.
— Finasteride, Not Tamsulosin, Increases Severity of Erectile Dysfunction and Decreases Testosterone Levels in Men with Benign Prostatic Hyperplasia. Abdulmaged M. Traish, Boston University School of Medicine; Karim Sultan Haider, Private Urology Practice, Bremerhaven; Gheorghe Doros, Boston University School of Public Health; Ahmad Haider, Private Urology Practice, Bremerhaven. Hormone Molecular Biology and Clinical Investigation, June 6, 2015.
Results: Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection. No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was 1 year or less for 26 of 34 trials (76%). Of 5704 men in the clinical data repository who were treated for AGA with finasteride, 1.25 mg/d or less, for [androgenetic alopecia], only 31% met inclusion criteria for the pivotal trials referenced in the manufacturer’s full prescribing information and 33% took finasteride for more than 1 year.
Conclusions and Relevance: Available toxicity information from clinical trials of finasteride in men with AGA is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of AGA, most would have been excluded from the pivotal studies that supported US Food and Drug Administration approval for AGA. Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.
The effects in the brain of finasteride…have been poorly explored. Therefore, the effects of a subchronic treatment of finasteride…and the consequences of its withdrawal on neuroactive steroid levels in plasma, cerebrospinal fluid and some brain regions…have been evaluated in male rats. After subchronic treatment…the following effects were detected: (i) depending on the compartment considered, alteration in the levels of neuroactive steroids, not only in 5alpha-reduced metabolites but also in its precursors and in neuroactive steroids from other steroidogenic pathways and (ii) upregulation of androgen receptor in the cerebral cortex and beta3 subunit of GABA-A receptor in the cerebellum. One month after the last treatment (i.e., withdrawal period), some of these effects persisted…Moreover, other changes in neuroactive steroid levels, steroid receptors…and GABA-A receptor subunits…were detected. These findings suggest that finasteride treatment may have broad consequences for brain function.
— Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and their Receptors in the Male Rat Brain: Silvia Giatti, PhD. Neuroendocrinology: International Journal for Basic and Clinical Studies on Neuroendocrine Relationships, Dec. 9, 2015
Recent postmarketing studies and the [FDA] have found that finasteride, 1 mg, for androgenic alopecia has been associated with persistent sexual and nonsexual adverse effects… The present study was designed to assess whether otherwise healthy former users of finasteride with persistent sexual adverse effects have a higher prevalence of low serum androgens and spermatogenic deficits… 3 of 19 participants (16%) [had] severe oligospermia (<5 million/mL). The mean and median motilities were 50% (23%) and 50%, respectively, with 4 of 9 participants (44%) having 2 confirmed low motility.
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.”
Conclusions: This study significantly extends understanding of the effects of long-term treatment with these drugs on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Treatment with finasteride or combined therapy was associated with worsening sexual function while treatment with doxazosin alone was associated with minimal negative impact, if any. Physicians should discuss with their patients the possible long-term effects of these drugs for lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function.
— Change in Sexual Function in Men with Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Associated with Long-Term Treatment with Doxazosin, Finasteride and Combined therapy. CW Fwu, Journal of Urology, June 2014.
Summary: “A substantial body of evidence exists which points to serious and potentially ill-health effects of [finasteride and dutasteride] therapy. These include loss or reduced libido, erectile dysfunction, orgasmic and ejaculatory dysfunction, development of high grade PCa tumors, potential negative cardiovascular events, and depression. The side effects are potentially harmful in some individuals and in young men may be persistent or irreversible. The argument that the benefits of these drugs outweighs the risks is slowly eroding in the face of new emerging scientific evidence from preclinical and clinical studies. The available data demonstrate that such drugs do pose serious adverse effects, especially in a subset of men who may have the predisposition to be affected severely. This is also corroborated by the overwhelming FDA disapproval of these drugs for the chemoprevention of PCa. The FDA mandated relabeling issued in 2011 equally points to the dark side of these drugs on human health. Physicians need to be aware of the adverse side effects of these drugs and are encouraged to share this information with their patients prior to commencing therapy with finasteride or dutasteride.
— The Dark Side of 5α-Reductase Inhibitors’ Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression. Traish, A.M. Korean J Urol. 2014 Jun;55(6):367-79. doi: 10.4111/kju.2014.55.6.367. Epub 2014 Jun 16.
Observations performed in a subset of patients treated for male pattern hair loss indicate that persistent sexual side effects as well as anxious/depressive symptomatology have been reported even after discontinuation of finasteride treatment. Due to the capability of finasteride to block the metabolismof progesterone (PROG) and/or testosterone (T) we have evaluated, by liquid chromatography–tandemmass spectrometry, the levels of several neuroactive steroids in paired plasma and cerebrospinal fluid (CSF) samples obtained from post-finasteride patients and in healthy controls. At the examination, post-finasteride patients reported muscular stiffness, cramps, tremors and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Although severity of the anxious/depressive symptoms was quite variable in their frequency, overall all the subjects had a fairly complex and constant neuropsychiatric pattern…The present observations show that altered levels of neuroactive steroids, associated with depression symptoms, are present in androgenic alopecia patients even after discontinuation of the finasteride treatment.
— Patients Treated for Male Pattern Hair with Finasteride Show, After Discontinuation of the Drug, Altered Levels of Neuroactive Steroids in Cerebrospinal Fluid and Plasma. Caruso, D., Melcangi R.C. J. Steroid Biochem. Mol. Biol. (2014)
Background: There have been reports for over a decade linking serotonin reuptake inhibitors, finasteride and isotretinoin with enduring sexual dysfunction after treatment stops.
Methods: We have selected 120 reports to RxISK.org reporting the problem and mined these for data on age, gender, drug of use, and impact of the problem.
Results: The data make it clear that the three drugs show extensive overlap in symptom profile, regardless of sex or country of origin.
Conclusions: The availability of 120 reports from over 20 countries add to the case for the validity of the syndrome. This is severe and enduring condition can result in death. An understanding of its physiology and an approach to treatment are needed.
Finasteride is still one of the most common therapeutic drugs prescribed for AGA, a distinctive alopecia pattern involving hairline recession and vertex balding, a condition more frequent with increasing age… However, treatment of young subjects is of increasing concern due to accumulating evidence that daily use of oral finasteride has several severe adverse effects. Our main finding was the assessment of a significant increase of AR nuclear levels in some types of cells, specifically, stromal and epithelial cells, in dermis samples of foreskin from patients with major sexual adverse side-effects long after use of finasteride (on average almost 5 years later). As our patients are suffering from symptoms suggestive of local androgens deficiency, it was important to assess if this phenomenon was due to intrinsic inability to express and/or translocate the AR into the cell nuclei, specifically in the genital tissues… Since finasteride inhibits T conversion into DHT, which is responsible for most androgen activity, it is plausible that prolonged finasteride use in predisposed individuals could simulate the effects of aging in young men. Since some of the effects of androgen inhibition cannot be reversed once local androgen levels are re-established, it is temping to speculate that patients could still suffer from adverse sexual effects several months or even permanently after finasteride discontinuation because of aging effects caused prematurely by androgens deprivation, namely by artificially reduced DHT concentrations.
— 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. Di Loreto, C., La Marra, F., Mazzon, G., Belgrano, E., Trombetta, C., Cauci, S. PLoS One. 2014 Jun 24;9(6):e100237. doi: 10.1371/journal.pone.0100237
Conclusions. Persistent adverse effects of finasteride in younger men include erectile dysfunction, low libido, lack of
orgasms, depression, and decreased alcohol consumption. One study has found lower levels of several neurosteroids
in this population. Out of the various persistent side effects, erectile dysfunction and decreased alcohol consumption
have been the most studied in animal models. Further research is needed on who is susceptible to the persistent
adverse side effects of finasteride and on the underlying mechanisms of the medication.
Background: There is a robust literature in rodents, but not in humans, on the interaction between finasteride and alcohol, particularly as it relates to neurosteroids. Finasteride has been shown to reduce alcohol intake and suppress alcohol preference in male mice. This study examines the role of finasteride in alcohol consumption in humans with male pattern hair loss.
Results: Of the 63 men who consumed at least 1 alcoholic beverage/wk prior to starting finasteride, 41 (65%) noted a decrease in their alcohol consumption after stopping finasteride. This reduction typically began before discontinuing finasteride. Twenty men (32%) reported no change in their alcohol consumption, and 2 men (3%) reported an increase in their alcohol consumption. For the 63 consumers of alcohol, the mean number (±SE) of alcoholic beverages/wk declined from 5.2 ± 0.7 before finasteride to 2.0 ± 0.3 after finasteride (p < 0.0001). A major study limitation is the lack of a comparison group.
Conclusions: In former male users of finasteride who developed persistent sexual side effects, 65% noticed a decline in their alcohol consumption as compared to baseline. This finding is consistent with finasteride’s ability to modulate alcohol intake in rodents. Further research is needed on the central nervous system effects of finasteride in humans.
— Decreased Alcohol Consumption Among Former Male Users of Finasteride with Persistent Sexual Side Effects: A Preliminary Report. Michael S. Irwig, M.D., F.A.C.E., assistant professor of medicine at the George Washington University School of Medicine and Health Sciences, and director of the Center for Andrology at The GW Medical Faculty Associates. Alcoholism: Clinical and Experimental Research. June 13, 2013. DOI: 10.1111/acer.12177.
Introduction: Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation.
Aim: A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology.
Conclusion: The present observations confirm that an impairment of neuroactive steroid levels, associated with depression symptoms, is still present in androgenic alopecia patients treated with finasteride despite the discontinuation of the treatment.
— Neuroactive Steroid Levels are Modified in Cerebrospinal Fluid and Plasma of Post-Finasteride Patients Showing Persistent Sexual Side Effects and Anxious/Depressive Symptomatology. Roberto Cosimo Melcangi PhD. The Journal of Sexual Medicine. Volume 10, Issue 10, pages 2598–2603, October 2013.
Expert opinion: Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5 – 9%. Decreased circulating dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARI. Patients receiving therapy with 5ARI should be counseled as to potential sexual and psychological adverse effects. Future clinical studies are needed to further investigate the sexual side effects associated with this class of drugs.
— Effects of 5-alpha Reductase inhibitors on erectile function, sexual desire and ejaculation. Serap Gur, Tulane University Health Sciences Center, January 2013, Vol. 12, No. 1 , Pages 81-90 (doi:10.1517/14740338.2013.742885)
- 5α-reductases are a family of isozymes that play a critical role in transformation not only of testosterone but also of progesterone, DOC, aldosterone and cortisol into a host of neuro-active steroids that regulate multitude of functions in human physiology…. the neuro-active steroid hormones modulate multitude of functions in human physiology encompassing regulation of sexual differentiation, neuro-protection, memory enhancement, anxiety, sleep and stress, among others.
- Until recently, the adverse effects of 5α -reductase inhibitor therapy were thought to be very minor and well tolerated (80, 81, 82). However, new information suggests that these drugs may impair sexual function including sexual desire, erectile and orgasmic function [Table 3](for review cf. 83, 84). Recent studies in animal models suggested that these agents alter penile tissue histo-architecture and nitric oxide synthase function in penile tissue and thus can contribute to erectile dysfunction (85, 86, 87).
- It is particularly important to note that in a subset of patients, the effects of these drugs are long lasting and may be irreversible (84). An association between use of these inhibitors and depression is also noted (88), suggesting potential adverse effect on the brain.
- A number of case reports have suggested that 5α-reductase inhibitors therapy is associated with angioedema ( 91); cataract and intraoperative floppy-iris syndrome (92), pseudoporphyria, (93),T cell–mediated acute localized exanthematous pustulosis (94) and gyncomastia and male breast cancer (28, 95).
- The recent introduced warnings on the drug labeling also suggests that increased awareness of the potential irreversible side effects of these agents [FDA].”
— 5α-Reductases in Human Physiology: An Unfolding Story. Abdulmaged M. Traish, PhD, MBA. Department of Urology, Boston University School of Medicine, Boston, Massachusetts, USA. Endocrine Practice (July 2012), 1530-891X (Print), 10.4158/EP12108.RA
- In a group of 54 otherwise healthy former users of finasteride who developed persistent sexual side effects that lasted for at least 3 months, 96% continued to experience these effects when reassessed 9–16 months (mean 14 months) later, raising the possibility of permanent effects.
- To explain the long-term neurological effects of finasteride, it is possible that reduced concentrations of neuroactive steroids are affecting the plasticity of neuronal architecture in regions of the brain responsible for sexual function.
- The most volunteered changes related to the urogenital system in terms of semen quality and decreased ejaculate volume, reduction in penis size, penile curvature or reduced sensation, fewer spontaneous erections, decreased testicular size, testicular pain, and prostatitis. Many subjects also noted changes to their mental abilities, sleeping patterns, and/or depressive symptoms. Many subjects reported a “disconnection” between the mental and physical aspects of sexual function.
- Further valuable research could determine who would be susceptible to finasteride through genetic studies of polymorphisms of 5a reductase and the androgen receptor. Further research with validated instruments is needed to study the nonsexual persistent side effects associated with finasteride.”
- In a group of 61 otherwise healthy former users of finasteride who developed persistent sexual side effects, depressive symptoms were present and categorized as mild in 11% of users, moderate in 28% of users, and severe in 36% of users. Suicidal thoughts were present in 39% of former finasteride users, and an additional 5% chose the statement “I would like to kill myself.”
- The corresponding rates of depressive symptoms and suicidal thoughts were significantly lower in a control group of young men with male pattern hair loss who had not used finasteride and who did not have any current or past psychiatric conditions or use of psychiatric medications.
- It turns out that finasteride crosses the blood-brain barrier and blocks the enzyme 5α-reductase, which reduces the concentrations of multiple neuroactive steroids derived not only from testosterone, but also from progesterone and deoxycorticosterone…. reduced concentrations of neuroactive steroids are associated with depression in several human studies.
- Although the effects of finasteride in the human brain are poorly understood, clinicians, as well as potential finasteride users, should be aware of the serious potential risks of this medication, especially as it is being used cosmetically to alter a normal age-related process. This is the first study to document suicidal thoughts in (former) users of finasteride.”
— Depressive Symptoms and Suicidal Thoughts Among Former Users of Finasteride With Persistent Sexual Side Effects. Michael S. Irwig, MD, Division of Endocrinology, Medical Faculty Associates and George Washington University. J Clin Psychiatry (August 2012), 10.4088/JCP.12m07887
- 5a-RIs therapy, while improving urinary symptoms in patients with BPH and may prevent hair loss, produce significant adverse effects in some individuals including loss of libido, ED, ejaculatory dysfunction, and potential depression. They are serious enough to preclude them from pursuing such therapy.
- The effects of these agents on vascular health should also be noted in light of recent findings that patients treated with 5a-RIs therapy had significant adverse cardiovascular events.
- These observations suggest that extreme caution should be exercised prior to prescribing 5a-RIs therapy to patients for hair growth or for BPH symptoms.”
— Adverse Side Effects of 5α-Reductase Inhibitors Therapy: Persistent Diminished Libido and Erectile Dysfunction and Depression in a Subset of Patients. Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML. J Sex Med. 2011 Mar;8(3):872-84.
- A subset of otherwise healthy men taking finasteride for MPHL developed persistent sexual side effects in temporal association with the medication. Most men developed sexual dysfunction in multiple domains with 94% experiencing low libido, 92% experiencing erectile dysfunction, 92% experiencing decreased arousal, and 69% experiencing problems with orgasm.
- The mean duration of the persistent sexual side effects was at least 40 months, with 20% of subjects reporting durations of over 6 years. The mean number of sexual episodes per month dropped from 25.8 before finasteride to 8.8 after finasteride (P < 0.0001). The total sexual dysfunction score increased from 7.4 to 21.6 for before and after finasteride use (P < 0.0001).
- Physicians treating MPHL should discuss the potential risk of persistent sexual side effects associated with finasteride.”