‘Safe and well-tolerated’: Arguments used to discredit reports of persistent adverse effects

Summary

It cannot simultaneously be true that finasteride is considered “safe” as a treatment for male pattern hair loss and that the drug causes severe and permanent sexual dysfunction in some men. Since 2011, dozens of papers have investigated its adverse effects, with some concluding that finasteride is safe for treating hair loss despite complaints from men who report persistent adverse effects after stopping the drug. Researchers who defend the drug as safe draw on the following arguments, which I have organized into four dimensions:

1. Received medical knowledge
1.1 The drug is safe and well-tolerated per clinical trials and clinician experience.

2. Credibility of patients and their reports
2.1 Patient reports reflect a nocebo effect.
2.2 Media coverage, internet forums, an advocacy group and litigation have stimulated reports of adverse events.
2.3 Patient complaints could reflect depression or psychopathology.

3. Quality of research
3.1 Studies are of low-quality and have methodological problems.
3.2 A causal link to finasteride has not been established.
3.3 Higher-quality research is needed, such as a randomized, placebo-controlled trial.

4. Disease definition
4.1 The proposed disease ‘post-finasteride syndrome’ is ill-defined and controversial.
4.2 No mechanism for permanent adverse effects can be conceived.

These researchers focus their efforts on defending the medical status quo and discrediting patient reports, while giving less attention to potential limitations and blind spots that might prevent detection and characterization of persistent adverse effects of finasteride.

Introduction

Propecia was approved for the treatment of androgenetic alopecia in 1997. Today, the mainstream medical view remains that finasteride is effective and safe for the treatment of androgenetic alopecia (AGA). In 2011, papers reported that adverse effects persisted in some men after they stopped taking the drug. One by Michael Irwig was titled: “Persistent sexual side effects of finasteride: could they be permanent?” If young, otherwise healthy men are indeed developing permanent sexual dysfunction because they took finasteride, this would be unacceptable. It cannot be the case that finasteride is safe, and that the drug can cause severe and permanent harms in some men. This sets up a kind of epistemological showdown between the medical status quo and patient reports.

Some researchers have defended the view that the drug is safe, in part by discrediting patient reports as invalid or suspect. They make logical arguments, citing previous research, and some authors do give consideration to patient reports. While this post does not contribute new evidence, it will show that a common set of arguments is repeatedly brought to defend medical orthodoxy, and that some researchers emphasize these arguments without giving serious consideration to alternative explanations. I contend that on the whole, these papers defend the status quo while making little or no effort to explore limitations which might prevent detection and understanding of persistent harms of finasteride.

Arguments used in defense of the status quo

There is a remarkable degree of overlap in arguments used across the papers considered here. I will introduce the common arguments and provide supporting quotations—with emphasis in bold text added. Supporting quotations are in order of publication date, with the most recent article first. For the full context, see the original studies in References.

Dimension 1: Received medical knowledge

Argument 1.1: Finasteride for AGA is safe and well-tolerated

Authors point out that large-scale clinical trials found an acceptable safety profile and that patients who reported adverse effects generally saw them resolve after stopping the drug. Some authors mentioned they have never, or only rarely, seen patients who report persistent adverse effects in their clinical practice.

Article excerpts

Clinical studies have demonstrated both a high efficacy of treatment and a very favorable safety profile

Trüeb et al., 2019

…in the Prostate Cancer Prevention Trial, none of the more than 17,000 participants experienced persistent sexual dysfunction or depression. In addition, the authors were able to demonstrate that finasteride only had a minimal effect on sexual dysfunction Once again, given the data from the hundreds of randomized, controlled trials, finasteride should still be considered a safe and well-tolerated medication. 

Singh & Avram, 2014

Our review shows that 5aRIs are a well tolerated and effective treatment for AGA.

Yim et al., 2014

Finasteride is a well-tolerated drug, and the only reported adverse effects involve sexual function… Finasteride-induced sexual dysfunction is nevertheless a benign condition that completely resolves after therapy is discontinued.

Tosti et al., 2004

Although subjects taking finasteride were informed about possible sexual side-effects, the results indicate that the sexual and erectile function of those subjects was not reduced compared with controls. These results are consistent with the experience of many dermatologists who do not see sexual or erectile dysfunction in their patients taking Propecia®.

Tosti et al., 2001

Dimension 2: Credibility of patient reports

Argument 2.1: Patient reports reflect a nocebo effect

The nocebo effect refers to “adverse effects of active treatments that cannot be attributed to the pharmacological or other active ingredients of the therapy” (Petrie et al., 2019 citing Barsky et al., 2002). Some researchers have argued that media stories and online discussions of finasteride could create the expectation of adverse effects, which prompts reports of adverse effects even though (according to this explanation) they are psychological in origin.

Article excerpts

An overlooked effect in research is the nocebo effect, or the phenomenon in which suggestions about inert substances actually bring about negative effects in a patient… The increased publicity of PFS can increase awareness and could increase the nocebo effect similar to the study mentioned above.

Baas et al., 2018

Moreover, a significant nocebo effect has been revealed in patients who were informed of potential sexual adverse effects before taking finasteride versus patients who were not informed.

Rezende et al., 2018

Although we excluded men who were depressed before initiating finasteride, we do not know whether the depressed mood in men in group 1 was causally related to finasteride use, alopecia itself, or nocebo effect.

Basaria et al., 2016

A significant placebo/nocebo effect has been documented among patients informed about possible side effects of finasteride and this may explain the high prevalence of reported sexual dysfunction including persistent dysfunction in subjects participating in Internet groups and blogs.

Fertig et al., 2016

…[I]n the 2007 study by Mondaini et al, a significant placebo [sic] effect was detected when patients were informed in advance about possible sexual dysfunction… Because a number of these patients were self-selected from the Internet, it would be difficult to determine if these individuals are experiencing a placebo [sic] effect because of possible counseling provided to these patients prior to initiating finasteride.

Singh & Avram, 2014

Our results support the clinical impression that sexual side effects are actually less common than is reported in clinical trials. This discrepancy may be attributable to the fact that subjects who enrolled in the clinical trials were informed about possible changes in their sexual function and were specifically asked about such changes at every visit, resulting in a higher percentage of reported adverse events than would normally occur. 

Tosti et al., 2004

Argument 2.2: Media coverage, online forums, a patient advocacy group and litigation have stimulated reports of adverse events

Similar to the nocebo argument, this argument embeds a view of patients as naïve, impressionable and unreliable:

  • Patients have been swayed by media stories to believe they have adverse effects;
  • Patients have been influenced by an advocacy group to believe they have adverse effects;
  • Patients are uninformed about health care, and therefore not qualified to report their health problems;
  • Patients may be motivated by involvement in litigation against Merck;
  • As a result of these influences, reports to FDA and other adverse event data reporting systems are biased and invalid.

[T]here may have been spurious reports from dissatisfied consumers or those involved in litigations against the pharmaceutical manufacturer. Health-related reports submitted by individuals without medical training may have led to biased or erroneous records which contain unverified symptoms.

Reports to FAERS from non-healthcare personnel increased dramatically following the FDA-mandated finasteride label change, associated with increased number of adverse effects included in each report.

Harrell et al., 2020

[T]he quality and quantity of reports in these databases can be influenced by reporting behavior, such as false reports submitted by patients who are dissatisfied or involved in litigation, or stimulated reporting affected by mass media. In fact, the sensitivity analyses by Nguyen and colleagues did reveal such reporting bias. The lack of suicidality signal observed for dustasteride…hints at a potential reporting bias unique to finasteride.

…[the] ultimate stratified analysis [in Nguyen et al., 2020] showing a significant signal after 2012 but none before 2012 supports the potential presence of a reporting bias or stimulated reporting accounting for the observed suicidality signal for finasteride.

Ho, 2020

…the disproportional reporting of suicidality associated with finasteride use could be owing to reporting bias. 

Highly publicized studies reported in the media around 2012 and efforts by organizations such as the Post-Finasteride Syndrome Foundation (founded in 2012) may have led to greater attention to and reporting of depression and suicidality suspected to be associated with finasteride use by health care professionals (ie, stimulated reporting) or induced a nocebo effect in patients.

…[O]ur sensitivity analyses shed light on potential biases that may confound the association between finasteride use and suicidality, namely, stimulated reporting, which should be further investigated.

In light of these exploratory findings, disproportional signals associated with finasteride may be attributed to reporting biases, namely, stimulated reporting, or to greater repercussions of adverse effects and/or inherent psychological morbidities among younger men. Suicidality and psychological adverse events associated with finasteride use by young patients undergoing treatment for alopecia and potential biases confounding this association merit further investigation.

Nguyen et al., 2020

The publicity around post-finasteride syndrome might have increased the reporting of symptoms... Finally, the number of adverse events reported for finasteride in a post-marketing database nearly quadrupled between 2011 and 2014, coinciding with changes to the US product label in 2012 and increased publicity.

Gray & Semla, 2019

When patients can self-report AE without medical training, the database becomes substandard in terms of assigning casual [sic] effects. Clearly, the potential biases in the FAERS database calls for a more scientifically rigorous process to determine the incidence of PFS and its putative persistence.

Baas et al., 2018

However, anecdotal reports and poorly designed studies have received increased media coverage concerning the persistence of ED and SD following cessation of even a small dose of finasteride, putatively termed the post-finasteride syndrome (PFS).

Gupta & McVary, 2017

Persistent side effects of finasteride have garnered much media attention. In fact, legal action has been taken with 742 Propecia (finasteride) lawsuits filed against the manufacturer Merck… The website propeciahelp.com has a link that offers visitors the possibility to join the lawsuit.

Fertig et al., 2016

Although it is acknowledged that patient-submitted reports are of good quality, spurious reports might be submitted due to patient dissatisfaction or involvement in litigations. In addition, stimulated reporting due to mass media news about [sexual dysfunction] risk with finasteride therapy could contribute to overrepresentation of [sexual dysfunction] reports for low-dose finasteride compared to all other drugs in the FAERS.

Ali et al., 2015

Several articles have been published in recent years, receiving a great deal of media and internet attention, describing these persistent sexual side effects as well as depression.

Singh & Avram, 2014

Argument 2.3: Complaints of adverse effects may reflect depression or psychopathology

Like the preceding two arguments, this argument embeds a view that patients are unreliable—but this one attributes this quality to a psychological disorder.

[The post-finasteride] syndrome is unclearly defined and often regarded as a type of delusional disorder that affects susceptible patients with alopecia rather than a true drug adverse effect.

Choi et al., 2021 (letter)

PFS may represent a delusional disorder of the somatic type, possibly on a background of a histrionic personality disorder, and with the potential of a mass psychogenic illness due to its media coverage...

Attention must be focused rather on the treatment of associated specific psychopathological disorders and related sexual symptoms with appropriate psychotherapy and specific psychotropic agents depending on the type of the underlying mental disorder (depressive, delusional, or somatoform disorder).

Trüeb, 2019

…Maffei et al. found the prevalence of personality disorders in patients with male pattern hair loss to be significantly higher than in the general population…

Specifically, patients with personality disorders tend to experience more distress from hair loss than nondisordered patients, since these individuals lack a secure sense of self and effective coping skills, and therefore may be particularly vulnerable to the adverse effects of pattern hair loss. Ultimately, these patients tend to be more difficult to handle with respect to the treatment of their hair loss:

Patient compliance issues are a problem in patients with paranoid, avoidant, or passive-aggressive (negativistic) personality disorders

Nocebo reactions are more frequent in patients with paranoid, passive-aggressive (negativistic), or histrionic personality disorders

Overvalued ideas are typical for patients with histrionic or narcissistic personality disorders.

Rezende et al., 2018

Basaria et al., 2016, commenting on correlations between depression scores and various brain areas:

This neural circuitry overlaps with functional abnormalities that have been identified in major depression. These 2 fMRI experiments suggest that there are underlying neurobiological abnormalities in symptomatic finasteride users, which can be linked to circuitry that has been implicated in both depression and in sexual arousal.

The men reporting persistent sexual symptoms had depressed mood, negative affectivity balance, and patterns of brain activity that correlated specifically with sexual and negative affective symptoms and included regions known to be involved in sexual function and depression, respectively.

…Furthermore, because men seeking treatment for alopecia have higher prevalence of depression and sexual dysfunction than the general population, it would be appropriate to ascertain history of depression or sexual dysfunction before starting treatment.

Basaria, 2016

However, men with AGA are often severely psychologically affected by their hair loss and therefore can be more susceptible to the psychological impact of possible sexual side effects. 

Tosti et al., 2004

Dimension 3: Quality of research

Argument 3.1: Studies are of low quality and have methodological problems

Defenders of the status quo argue that research on persistent adverse effects of finasteride has limitations including selection bias, lack of a control group and the use of retrospective data.

Article excerpts

Post-finasteride syndrome originates from post-marketing reports, case series, and uncontrolled surveys of targeted patient populations recruited from advocacy websites. This low quality evidence does not support a causal link between finasteride and persistent symptoms. 

Gray & Semla, 2019

Quality studies are a major problem in assessing the validity of PFS associated with finasteride. Many of these studies are inherently biased (particularly with selection bias), retrospective in nature, lack a control group, and employ unvalidated questionnaires. Additionally, in many of the studies we do not know the sexual and psychological histories which may contribute to understanding the symptoms. One such oft-quoted study was a survey of 54 men treated with finasteride 1 mg recruited via an online survey via a website supported by an advocacy group for problems with finasteride, and reported persistent sexual dysfunction ≥16 months.

Baas et al., 2018

The concept [of post-finasteride syndrome] 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.

Rezende et al., 2018

However, despite a large number of patients seeking medical care, ongoing litigation, and a vast amount of anecdotal information available on the internet, even the basic pathophysiologic attributes of this condition…have not been rigorously investigated. Therefore, the underlying pathophysiologic mechanisms remain unknown.

Basaria et al., 2016

A literature review of adverse side effects associated with 5αRIs shows that persistent sexual side effects were only documented in low-quality studies with strong bias selection as participants were part of an Internet blog. The only high-quality study documenting persistent sexual side effects showed that these were more frequent in the placebo than in the treatment group, implying that the effects were not necessarily related to the treatment.

Psychiatric side effects were only documented in moderate- or low-quality studies including studies performed on patients with sexual side effects, which could influence patient’s mood. Most of these studies recruited patients through the same Internet patient website.

Fertig et al., 2016

A major concern is the level of selection bias among the participants. Many of the individuals were recruited from an Internet website for individuals with persistent sexual side effects after using finasteride. It is probable that these individuals are more seriously affected by sexuality or have more severe sexual dysfunction and, thus, are more likely to participate in and seek out the study…

Moreover, these were retrospective studies with no placebo control. Given the retrospective nature of these studies, we cannot ascertain the true incidence of persistent sexual dysfunction and depression in finasteride users.

Singh & Avram, 2014

Argument 3.2: Causation has not been established

This argument relates to the previous argument, as well as those about the nocebo effect and stimulated reporting. It points out that finasteride is not necessarily the cause of adverse effects patients have reported. It could be that these men were already depressed or had sexual dysfunction, and that prior use of finasteride could have been coincidental.

Article excerpts

Definitive causal inferences cannot be drawn from this kind of pharmacovigilance study, and certainly, the signals for suicidality and psychological adverse events that Nguyen and colleagues identified for finasteride should not be mistaken for proof that there is a causal association between the 2, due to the inherent biases described.

Ho, 2020

The physical effects of [animal model] findings are speculative, and remain unvalidated as causally related to 5ARI exposure given the poor study design of the aforementioned studies.

Given the nature of the FAERS reporting, any condition may have been attributed to finasteride. For example, a patient could claim to have worsened sexual function after becoming aware of potential side effects, change in relationship status, other psychosocial events, or social media interactions. In the absence of objective findings, it is impossible to attribute causality to use of 5ARIs.

Limitations of the FAERS database are numerous including self-selection bias, the lack of verifiable AE, lack of baseline function and knowledge of prior to drug exposure. No direct causation can be made from the reported use of 5ARIs. …it is not possible to causally link the AEs with finasteride exposure as controlled studies are lacking.

Baas et al., 2018

Because of the cross-sectional nature of the study, a causal relation between prior finasteride use and persistent sexual symptoms, mood changes, cognitive complaints, or fMRI findings cannot be inferred. It is possible that the depressive symptoms and prior finasteride use are coincidental or that the depressed mood may contribute to sexual dysfunction.

Basaria et al., 2016

From these studies [by Irwig et al] alone, we cannot conclude that finasteride is definitively linked to persistent sexual dysfunction and depression.

Singh & Avram, 2014

Argument 3.3: Higher-quality research is needed, such as a randomized, placebo-controlled trial

It is a common refrain of many scientific papers to say “more research is needed.” In this set of papers, researchers call for higher-quality research, but do not signal any intention to carry out such research.

Future prospective studies are required to evaluate the true rates of AEs to each monotherapy.

Harrell, 2020

[The findings by Nguyen et al., 2020] should stimulate further large-scale prospective pharmacoepidemiologic studies designed specifically to evaluate these potential adverse events in young patients using finasteride for treatment of androgenetic alopecia.

Ho, 2020

We need placebo controlled trials using validated questionnaires and long term follow-up after treatment to examine persistence of symptoms…

Gray & Semla, 2019

PFS requires further research with placebo controlled, randomized trials with validated questionnaires and prior sexual and mental health histories followed for a sufficient length of time.

Baas et al., 2018

The possibility that a medication as prevalent as finasteride causes irreversible SD is alarming, especially when the treatment population includes younger, otherwise healthy men. However, good science with appropriate controls and follow up is necessary to elucidate whether the effect is real and to ensure we do not shun effective therapy because of confirmation and selection bias.

Gupta & McVary, 2017

Persistent sexual and psychiatric side effects after 5αRIs are not documented by high-quality studies, and prospective studies to establish true incidence and frequency of the problem are really needed.

Fertig et al., 2016

It is essential that further research is performed, in the form of randomized control trials, to further evaluate if there are any unique characteristics in these individuals suffering from prolonged sexual dysfunction and severe depression after using finasteride. These future double-blind, placebo-controlled trials are necessary to conclude if these findings by Irwig et al are “a red herring” or a potentially rare but serious side effect about which we should counsel our patients.

Singh & Avram, 2014

Dimension 4: Disease definition

Argument 4.1: The proposed disorder is ill-defined and controversial

This argument responds to the proposal of a “post-finasteride syndrome,” an entity which has not been endorsed by any official medical body.

Article excerpts

[Post-finasteride syndrome] remains a contentious and poorly understood subset of potential adverse effects associated with 5ARIs, attributable to its unclear biological mechanism and absence of clear epidemiological data, and a large variability in time to depressive symptomatology in animal studies.

Harrell, 2020

Post-finasteride syndrome is an ill defined and controversial syndrome associated with a constellation of sexual, physical, and psychological symptoms that develop during or after finasteride exposure and persist after discontinuation.

Gray & Semla, 2019

[Post-finasteride syndrome] demonstrates analogies to controversial “mystery syndromes” as amalgam illness, multiple chemical sensitivity, Morgellons disease, and Koro: the symptoms cannot be adequately explained biologically, and the frequency of consultations for the respective condition parallels the media coverage, which points to a high degree of suggestibility.

Trüeb et al., 2019

Postfinasteride syndrome (PFS) is a controversial and ill-defined spectrum of symptoms in 3 categories: sexual, physical, and psychological that putatively arise and persist despite finasteride exposure and cessation.

Baas, 2018

Argument 4.2: No mechanism can be conceived

This argument implies that if a disease mechanism cannot be conceived, the proposed disease cannot be valid. Several of these articles discount the proposed disorder because they cannot answer the question: “Why?”

…the symptoms cannot be adequately explained biologically…

Trüeb et al., 2019

The responsible mechanism of action for the associated PFS symptoms is a matter of speculation, and some have theorized that more psycho and/or social issues are at play citing younger men with MPB may be a vulnerable population with self-image concerns.

[…] It is particularly interesting that the higher rates of AEs are associated with lower drug doses… [W]hy AE’s were not equally reported in both the 5 mg and 1 mg dose in the FAERS data by frequency is not known. We are not aware of any similar association in the literature of a drug induced AE in which the lower dose induces more events…

Baas et al., 2018

Biologically, the mechanism of action in PFS is questionable. While the biology of loss of libido with finasteride can be explained by a resultant dearth of dihydrotestosterone (DHT), the lack of DHT does not explain why this effect is not reversible when finasteride is stopped, 5a-reductase is no longer inhibited, and DHT returns to baseline levels. ED is less directly related to androgen levels and is more indicative of vascular health. Vascular integrity requires a significant time to deteriorate and almost certainly would not occur within 1 yr of starting treatment, as is the case with most reports of PFS, without some pre-existing vascular disease.

Gupta & McVary, 2017

It is unclear why only a subset of finasteride users experience persistent sexual symptoms and low mood. 

Basaria et al., 2016

Assessing arguments in defense of the status quo

As mentioned above, this post does not add new evidence, and so cannot prove or disprove any of the above arguments. My purpose has rather been to show how some researchers defend the status quo by endorsing received medical knowledge; discrediting patient reports and published research; and calling ‘post-finasteride syndrome’ ill-defined and lacking a plausible mechanism.

It is sensible to seek a mechanism and definition of the disease; and reasonable to critically evaluate patient reports. At the same time, it is revealing that these researchers do not give much attention to the limitations of current methods and measures to detect and characterize what has been reported by patients. Potential limitations and blind spots include:

  • Past clinical trials may not have adequately detected sexual and psychological adverse effects because of social stigma surrounding these conditions;
  • Adverse events may be stimulated but also true—and stimulation may be necessary because of stigma surrounding sexual and psychological adverse events;
  • Conventional lab tests may not detect the pathophysiology, which might involve neuroendocrine disruption, androgen receptor dysregulation or neurological damage. Numerous rare diseases have been accepted as valid without a clear biomarker (such as ME/CFS).
  • We do not have a complete understanding of finasteride’s effects on the body (including individual differences in response to the drug);
  • We have a limited understanding of the neurobiology of sexual desire and arousal, and of the neuroendocrine system on which finasteride operates;
  • Younger men, with a different androgenic profile to older men, may be at higher risk of persistent adverse effects of finasteride. Thus trials and studies of older men may not be applicable.

Finasteride as the cause of reported persistent adverse effects remains a plausible and reasonably parsimonious explanation, but the researchers quoted above are at pains to refute it. One would like to think that science is neutral and objective, but like any human endeavor it is subject to bias (see Science Fictions by Stuart Ritchie). The following interests and biases could be in play among researchers and clinician-scientists:

  • medical guild interests: putting the interests of medical professionals before those of patients (see Chervenak, 2018);
  • professional hubris: doctors have authority because they are doctors;
  • paternalism towards patients: “doctor knows best” when it comes to patient complaints;
  • reputational and legal concerns: if a drug was previously defended but later turns out to be unsafe, it would damage the profession’s reputation and provoke legal action;
  • inertia and conservatism in relation to medical knowledge: medicine can be slow to update its position on diseases and treatments as new evidence emerges.

I list these not to make any accusation against authors cited above, but as a reminder that science is a human endeavor that is subject to conflicts of interest and bias, and published peer-reviewed research is not necessarily definitive. Like any source of evidence, published studies should be viewed with a critical lens. We might bear in mind that in the history of science and medicine, it is typically easier and safer to defend the status quo than challenge it.

The fact remains that we have no biomarker or effective treatment for men who report persistent adverse effects after stopping finasteride. This is an exasperating state of affairs for patients, researchers and doctors alike. Until we have more definitive evidence, men who have taken finasteride, doctors and researchers will remain divided by their attitude towards this concerning area of uncertainty.

References

Ali AK, Heran BS, Etminan M. Persistent Sexual Dysfunction and Suicidal Ideation in Young Men Treated with Low-Dose Finasteride: A Pharmacovigilance Study. Pharmacotherapy. 2015;35(7):687-695. doi:10.1002/phar.1612 | PubMed

Baas WR, Butcher MJ, Lwin A, Holland B, Herberts M, Clemons J, Delfino K, Althof S, Kohler TS, McVary KT. A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Postfinasteride Syndrome. Urology. 2018 Oct;120:143-149. doi:10.1016/j.urology.2018.06.022 | PubMed

Basaria S, Jasuja R, Huang G, Wharton W, Pan H, Pencina K, Li Z, Travison TG, Bhawan J, Gonthier R, Labrie F, Dury AY, Serra C, Papazian A, O’Leary M, Amr S, Storer TW, Stern E, Bhasin S. Characteristics of Men Who Report Persistent Sexual Symptoms After Finasteride Use for Hair Loss. J Clin Endocrinol Metab. 2016;101(12):4669-4680. doi:10.1210/jc.2016-2726 | PubMed

Chervenak FA, McCullough LB, Hale RW. Guild interests: an insidious threat to professionalism in obstetrics and gynecology. Am J Obstet Gynecol. 2018 Dec;219(6):581-584. doi:10.1016/j.ajog.2018.09.007 | PubMed

Choi JW, Huh CH, Choi GS. [Letter] Association of Hair Loss With Suicidality and Psychological Adverse Events vs Finasteride Use. JAMA Dermatol. 2021 May 5. doi:10.1001/jamadermatol.2021.1001 | PubMed

Coskuner ER, Ozkan B, Culha MG. Sexual Problems of Men With Androgenic Alopecia Treated With 5-Alpha Reductase Inhibitors. Sex Med Rev. 2019;7(2):277-282. doi:10.1016/j.sxmr.2018.07.003 | PubMed

Fertig R, Shapiro J, Bergfeld W, Tosti A. Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome. Skin Appendage Disord. 2016;2(3-4):120-129. doi:10.1159/000450617 | PubMed

Gray SL, Semla TP. Post-finasteride syndrome. BMJ. 2019;366:l5047. doi:10.1136/bmj.l5047 | PubMed

Gupta NK, McVary KT. Re: Risk of Erectile Dysfunction Associated with Use of 5α-Reductase Inhibitors for Benign Prostatic Hyperplasia or Alopecia: Population Based Studies Using the Clinical Practice Research Datalink. Eur Urol. 2017;72(2):317–318. doi:10.1016/j.eururo.2017.03.043 | PubMed

Harrell MB, Ho K, Te AE, Kaplan SA, Chughtai B. An evaluation of the federal adverse events reporting system data on adverse effects of 5-alpha reductase inhibitors. World J Urol. 2020;10.1007/s00345-020-03314-9. doi:10.1007/s00345-020-03314-9 | PubMed

Ho RS. Ongoing Concerns Regarding Finasteride for the Treatment of Male-Pattern Androgenetic Alopecia. JAMA Dermatol. 2020 Nov 11. doi:10.1001/jamadermatol.2020.3384 | PubMed

Irwig MS. Persistent sexual side effects of finasteride: could they be permanent? J Sex Med. 2012 Nov;9(11):2927-32. doi:10.1111/j.1743-6109.2012.02846.x | PubMed

Kuhn, T. The Structure of Scientific Revolutions. University of Chicago Press; 1962.

Nguyen DD, Marchese M, Cone EB, Paciotti M, Basaria S, Bhojani N, Trinh QD. Investigation of Suicidality and Psychological Adverse Events in Patients Treated With Finasteride. JAMA Dermatol. 2020 Nov 11;157(1):35–42. doi:10.1001/jamadermatol.2020.3385 | PubMed

Petrie KJ, Rief W. Psychobiological Mechanisms of Placebo and Nocebo Effects: Pathways to Improve Treatments and Reduce Side Effects. Annu Rev Psychol. 2019 Jan 4;70:599-625. doi:10.1146/annurev-psych-010418-102907 | PubMed

Rezende HD, Dias MFRG, Trüeb RM. A Comment on the Post-Finasteride Syndrome. Int J Trichology. 2018;10(6):255-261. doi:10.4103/ijt.ijt_61_18 | Free PMC Article

Ritchie, S. Science Fictions. Metropolitan Books / Henry Holt; 2020.

Singh MK, Avram M. Persistent sexual dysfunction and depression in finasteride users for male pattern hair loss: a serious concern or red herring? J Clin Aesthet Dermatol. 2014;7(12):51-55. PubMed

Tosti A, Pazzaglia M, Soli M, et al. Evaluation of sexual function with an international index of erectile function in subjects taking finasteride for androgenetic alopecia. Arch Dermatol. 2004;140(7):857-858. doi:10.1001/archderm.140.7.857 | PubMed

Tosti A, Piraccini BM, Soli M. Evaluation of sexual function in subjects taking finasteride for the treatment of androgenetic alopecia. J Eur Acad Dermatol Venereol. 2001;15(5):418-421. doi:10.1046/j.1468-3083.2001.00315.x | PubMed

Trüeb RM, Régnier A, Dutra Rezende H, Gavazzoni Dias MFR. Post-Finasteride Syndrome: An Induced Delusional Disorder with the Potential of a Mass Psychogenic Illness? Skin Appendage Disord. 2019;5(5):320-326. doi:10.1159/000497362 | PubMed

Yim E, Nole KL, Tosti A. 5α-Reductase inhibitors in androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. 2014;21(6):493-498. doi:10.1097/MED.0000000000000112 | PubMed