Response to Dr. Ralph Trüeb’s writings on post-finasteride syndrome

A drug-induced syndrome is all in the mind, a Swiss doctor wrote. Editors of the journals had past ties to the drug maker.

Men turn to finasteride to try to save their hair, but they might end up with a severe and lasting disability.1 There are countless stories online, usually anonymous because of the embarrassing subject matter. Here is one posted to the Ask a Patient website in 2007:

I actually had increased sex drive while using propecia [finasteride] for 3 years. However, I suddenly lost my sex drive in June 2007 and it has not recovered for 18 months now since I quit propecia. I have lost all my normal morning erections and my sexual desire is completely absent. Nothing in life is exciting anymore without my sexual drive and energy. You will feel apathetic and emotionally blunt without your libido. It is a feeling of melancholy passiveness. I’m wondering if I’ll ever have my life back.2

If a young man in this position sees a doctor, he might be told he is merely depressed, already had sexual dysfunction before starting finasteride, or read too many horror stories online. Other doctors recognize this as post-finasteride syndrome, a long-term disability affecting sexuality, mental state, thought processes and more.3

Is it caused by the drug? Six years ago, a Swiss dermatologist named Dr. Ralph Trüeb stepped into the breach, writing a series of six articles about post-finasteride syndrome (four with co-authors).4-9 One was a case report suggesting the syndrome is a delusional disorder linked to a personality disorder and other psychological factors.6 On a close reading, these articles reveal nothing about the syndrome—indeed, they seem designed to stir up confusion and doubt—but put Trüeb’s own biases on display. Meanwhile, at the journals, editors had numerous ties to the author and to the pharmaceutical industry, including past involvement in Merck’s rollout of finasteride for hair loss under the brand name Propecia.

A “highly charged” encounter

The case report describes a 25-year-old patient seen in Dr. Trüeb’s clinic near Zürich. The case summary ends with these lines:

…[T]he patient expressed his belief in suffering from post-finasteride syndrome with unusual persistence, despite all rational argumentation against it, and was humorless and oversensitive about his concern. Every attempt to challenge his conviction aroused a strong emotional reaction, with irritability and hostility. He expressed a heightened sense of self-reference, and the atmosphere surrounding his belief was highly charged. He denied both a history of depression or a current depressive episode.

The authors go on to compare his condition to “mystery syndromes” and observe that “mass hysteria of genital shrinkage anxiety has a history in Africa, Asia and in the late Middle Ages of Europe.” They eventually propose that the syndrome could be a delusion emerging from a histrionic personality disorder, negative expectations and social media activity.6 For a time, the article’s sensational title appeared near the top of Google search results for “post-finasteride syndrome”: “Post-finasteride syndrome: an induced delusional disorder with the potential of a mass psychogenic illness?”

Dr. Trüeb is a notable figure in dermatology and hair disorders. The Swiss physician has published over 350 articles, authored books including The Difficult Hair Loss Patient, and edited a hefty textbook entitled Hair Growth and Disorders. His interests include the hair of religious and historical figures (his articles include “Beneath the Nimbus—The Hair of the Saints” and “Why Henry III of Navarre’s Hair Probably Did Not Turn White Overnight”). Displaying cosmopolitan tastes, his writings bear epigraphs from Carrie Fisher, Albert Einstein and Seneca.

Trüeb’s first article on lasting effects of finasteride, published in 2017, is dispassionate and prudent.4 The syndrome has “very distinctive and relatively homogenous symptoms,” he observes. He mentions lasting effects of other drugs and notes finasteride’s impact on neural pathways. The article is reasonable throughout and expresses no contempt for the patient.

In the next article, published in 2018, the first signs of exasperation appear.5 Trüeb and co-authors admit that post-finasteride syndrome is a “problem that has to be dealt with,” yet “low-quality studies” neither confirm nor deny its validity. The tone shifts erratically from open-minded to condescending, then humane, calling for understanding and rapport to “[maximize] patient benefit and safety.”

Personality disorders come up for the first time. The authors suggest the syndrome may emerge in patients with one of three disordered personality types:

• Suspicious, with grandiose sense of self-importance, obsessive, and socially withdrawn
• Impulsive, identity disordered, and socially maladjusted
• Dramatic, emotional, and dependent

These patients “lack a secure sense of self and effective coping skills,” they write, and quote from Trüeb’s book, The Difficult Hair Loss Patient.11

• Patient compliance issues are a problem in patients with paranoid, avoidant, or passive-aggressive (negativistic) personality disorders
• Nocebo reactions [side effects due to negative expectations] 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.

These remarks serve to deflect attention away from patients’ experiences and onto patients themselves, who are now tainted with psychological problems. Yet the authors urge diplomacy: “The physician should be careful not to be judgmental, ridiculing, or scolding because this may rapidly close down communication and potentially aggravate the situation.” This new idea—that post-finasteride syndrome is the product of a defective personality—will be developed and reiterated in four more articles.6-9

Competing interests and cozy relations

It’s worth pausing to look at how these articles came to be published, because editors at two journals had prior involvement in Merck’s rollout of Propecia along with other ties to the pharmaceutical industry. First, a crash course on the editorial process at medical journals. When a manuscript arrives, editors decide whether to consider it for publication. If it passes this first step, it is forwarded to outside experts for review. While reviewers decide whether to accept the article, editors have influence too as they orchestrate the publication process. For example, they might select reviewers and broker disagreements. Given this influence, it is worth understanding their professional ties.

At two journals where Trüeb’s articles appeared, editors included prominent physicians who moved between the worlds of academic medicine and the pharmaceutical industry. At the International Journal of Trichology, where the second article appeared,5 five editors had supported Merck’s launch of Propecia as investigators, co-authors and speakers (see a table of competing interests). Meanwhile, Trüeb had ties to these editors and the journal. He had edited a textbook by Dr. David Whiting, a Section Editor. Trüeb has published 36 articles in the journal to date, served as a Regional Editor in 2017, and holds this role today according to the journal’s website. Trüeb’s six articles on post-finasteride syndrome cited articles by all five editors.

At the journal Skin Appendage Disorders, where Trüeb’s last four articles were published, there was again a tight network linking Trüeb, the journal and editorial personnel, who in turn had previously supported Merck’s rollout of Propecia. Dr. Antonella Tosti, co-Editor-in-Chief, had worked with Trüeb as co-editor of Hair Growth and Disorders. Tosti had also co-authored an article on finasteride with Merck researchers in 200011 and served as a consultant and speaker for the company.12 Dr. Jerry Shapiro, a member of the Editorial Board, served as an investigator, consultant, co-author and speaker for the launch of Propecia.12,13 Finally, Trüeb has published 21 articles in this journal and has served on the Editorial Board since 2015, the earliest year that could be confirmed.

Trüeb’s articles rely heavily on a 2016 review co-authored by Tosti and Shapiro in Skin Appendage Disorders (as a reminder, both Tosti and Shapiro also have editorial roles at the journal, with Tosti as one of two Editors-in-Chief).12 The review declared that post-finasteride syndrome is documented in “low-quality studies with strong bias,” while published results of Merck’s clinical trials were deemed high-quality.

The network of relationships surrounding Skin Appendage Disorders is shown in the diagram.

The network surrounding Skin Appendage Disorders. All four of Trüeb’s articles on post-finasteride syndrome in this journal cited Fertig et al, 2016. Two co-authors, Dr. Tosti and Dr. Shapiro, had editorial roles at this journal as well as former roles in Merck’s launch of Propecia. (1) Dr. Tosti has also disclosed roles as a speaker and consultant for Merck,12 but it could not be confirmed whether this was specifically in support of Propecia for male pattern hair loss.

Beyond ties to Merck, Tosti and Shapiro have disclosed current or recent relationships with some 22 pharmaceutical and consumer product companies between them, from startups to household names like Pfizer and Procter & Gamble, as shown in the second diagram. Since 2020, both have been advisors to telehealth company Keeps, which prescribes finasteride for hair loss.

Industry relationships of Dr. Antonella Tosti and Dr. Jerry Shapiro. Both physicians had past roles in Merck’s rollout of Propecia. They have disclosed current or recent ties to 22 other pharmaceutical companies between them, in various roles as principal investigator, consultant, advisory board member, speaker, founder and stockholder. They have common ties to seven companies including Thirty Madison, owner of the fast-growing telehealth company Keeps, which prescribes finasteride for hair loss (they have been listed as advisors to Keeps since July 2020). Red stars highlight indirect links from Trüeb’s articles to the journal’s editors, the telehealth sector, and prior involvement in Merck’s launch of Propecia. (1) It could not be confirmed whether Dr. Tosti’s disclosed roles as a speaker and consultant for Merck were specifically in support of Propecia for male pattern hair loss. Sources: disclosures in journal articles.12,13,17–19

Tosti and Shapiro are influential in the field of dermatology, holding roles as professors, physicians, investigators, editors, board members and consultants to industry. They have published practice guidelines for the treatment of hair loss,14–16 and Shapiro has disclosed a relationship with UpToDate, a leading publisher of clinical guidance.12 Their extensive ties are characteristic of the key opinion leader (KOL), an influential figure who may promote a specific drug to their colleagues under agreement with the drug maker. KOL activities are billed as research or education, but serve a marketing purpose.20 When news comes that a widely used drug might cause patients irreversible harm, it threatens all who have a stake in the status quo—physicians, the pharmaceutical industry, professional associations, journals and regulators. Post-finasteride syndrome constitutes such a threat.

Reliance on impressions and associations

We return to Trüeb’s series of articles on post-finasteride syndrome. The only substantial new information across all six articles is a brief case summary.6 From there, the dermatologists mused at length about mental disorders, finally suggesting that the 26-year-old patient may have had a delusional disorder. Along the way, they criticized studies on post-finasteride syndrome as low-quality and biased, and belittled work by “non-dermatologists.”6 Their approach, heavy on impressions and associations, contrasts with a 2016 report on two cases of post-finasteride syndrome in Brazil, in which the physicians ordered a penile ultrasound examination, MRI scan, and genetic and hormonal tests. Those physicians administered multiple treatments and followed the patients for up to three months.21

Illusory foundations

Trüeb’s argument relies heavily on two studies, one on personality disorders (PDs) and the other on the nocebo effect (explained below). Upon careful reading, a 1994 study exploring personality disorders in hair loss patients provides no support for his claims.22 See the box for a detailed explanation.

Briefly, the paper reports that a stunning 79% of men seeking treatment for hair loss had a PD based on a questionnaire—and yet had no history of mental illness before entering the study. To explain this curious result, the authors speculated that the men developed a personality disorder only after starting to lose their hair, because of a “maladaptive” personality. No other studies could be found to support these findings, except for an earlier study by the same group with a major confounding factor: 79% of subjects were experiencing stress-related hair loss.23 (Another study, not cited by Trüeb, found that the prevailing personality traits in men with post-finasteride syndrome were extroversion, agreeableness, emotional stability and openness.24)

BOX: Technical discussion of Maffei et al, 1994

In the 1990s, researchers in Italy administered a questionnaire to assess personality disorders (PDs) in a population of 116 men and women seeking treatment for hair loss. They found that 79% of the men had a PD. From this data, they derived three common personality profiles called factors. The table shows how strongly each factor was expressed in men and women.

Since there was no control group, these findings only reveal differences within this study population, not differences from a general population. Similarly, the factors don’t have meaning outside the study because they were derived from questionnaire responses. Gender-specific correlations have limited value because the factors were derived from a mixed-gender population. Finally, if the questionnaire is unreliable, the factors are meaningless. (Can we trust the finding that nearly four in five men in the study had a PD even though they had no prior psychiatric history?)

Table 2 from Maffei et al., 1994. Scores indicate correlation with each Personality Disorder factor by gender. The range is –1.00 to 1.00.

Putting aside those limitations, two of the PD factors (F1 & F3) were negatively correlated with males, while the other (F2) had a slim positive correlation of 0.16 and a high standard deviation of 0.99. Moreover, this factor only captured 13% of variance in the sample. Factor 2 was expressed more in men than women in this sample but has no meaning beyond this population. No conclusions can be drawn about whether men seeking treatment for hair loss in the real world have these tendencies.

A separate questionnaire assessed subjects’ psychological symptoms (PS) and mapped them back to PD factors. The authors found relationships across the whole population of men and women; however, findings for the population cannot be applied to the male subgroup (and correlations of males to PD factors were already unremarkable).

Finally, Trüeb contends there is a higher rate of histrionic personality disorder (HPD) among patients with male pattern hair loss5 and frequently links men with post-finasteride syndrome to HPD.6 There is no support for these claims in Maffei et al, as the authors did not report on specific personality disorders found in the questionnaire. The centerpiece of Trüeb’s theory therefore finds no support in this study.

Trüeb leans heavily on the nocebo effect, in which a patient’s negative expectations about a drug might bring about side effects. He repeatedly cites a 2007 study in which one group of men was advised about possible sexual side effects before they started taking finasteride, while the other group did not receive any advance notice. During treatment, the group with advance notice reported side effects at a much higher rate.25 This study is irrelevant for Trüeb’s purposes, because side effects were reported while patients were taking the drug. Post-finasteride syndrome is not a case of side effects while taking a drug; it refers to dysfunctions present at least three months after stopping the drug. In a literature search, no evidence could be found for a nocebo effect after patients stopped taking finasteride, or any other drug.

Trüeb sought to link the alleged nocebo effect to personality disorders,6 citing his own 2013 paper, “The difficult hair loss patient: a particular challenge.”26 Yet it offers only a recommendation: “[S]ome patients with somatoform disorder and specific personality disorders…are more prone to nocebo reactions and should be recognized as such.” No evidence is cited, so the connection between personality disorders and a nocebo effect remains speculation.

Flight of ideas

Instead of making a logical argument, Trüeb’s six articles rely on free association. In the case report he describes koro, a culture-bound syndrome found in Asia, in which men believe their genitals are retracting into their body. Because a symptom of post-finasteride syndrome is penile shrinkage, Trüeb likens the syndrome to koro, ignoring empirical evidence that finasteride can reduce penis size27 and overlooking a plausible biological basis: the drug suppresses a male sex hormone crucial in the differentiation of male genitals in fetal development.

The authors pull from a grab bag of concepts including PDs, “difficult hair loss patients,” “delusional disorder of the somatic type,” histrionic personality disorder, conversion disorder, and social contagion via the internet. This excerpt shows a jumble of impressions with no clear destination and no basis in fact:

Events which, to others, are nonsignificant are of enormous significance to [the delusional patient], and the atmosphere surrounding the delusions is highly charged.

An induced delusional disorder is one in which symptoms of a delusional belief are transmitted from one individual to another. The same syndrome shared by more than two people (folie à deux) may be called folie à trois, à quatre, even à plusieurs, or ultimately folie “à l’Internet.” Finally, when a large number of people may come to believe obviously false and potentially distressing things based purely on hearsay, these beliefs are labelled by the psychiatric profession as mass psychogenic illness or mass hysteria.

The high degree of suggestibility points to yet another possible underlying psychopathological disorder: histrionic personality disorder.6

The passage recalls an older term in psychiatry, flight of ideas, defined as “a rapid shifting of ideas with only superficial associative connections between them that is expressed as a disconnected rambling from subject to subject and occurs especially in the manic phase of bipolar disorder.”28 By the authors’ own associative logic, we might say that their illogical claims suggest a possible mental disorder.

Self-sabotage

Trüeb exhibits some of the same traits he pins on the patient. He calls the patient histrionic and irrational—even while casting himself as a distinguished psychologist (without apparent credentials) and stringing together bizarre ideas. He describes the patient as irritable and hostile, yet the articles betray hostility towards the patient. He reports that the patient fixated on one idea and would not respond to reason—yet the physician himself shows a certain fixation, having published six articles on this syndrome in as many years.

It happens that Trüeb just published an article called “Ignorism” on the pitfalls of ignoring information that could change one’s conclusions.29 Leaving out information about charged topics is “reprehensible,” he writes. Yet the series on post-finasteride syndrome practices does just this. Studies have demonstrated penile damage in animals treated with finasteride: ignored. The Swiss doctor’s own behavior could have influenced the encounter with his patient: ignored. In a Japanese trial, the methodology and cultural setting might have understated safety concerns: ignored. There is no evidence for a post-drug nocebo effect: ignored. Many legitimate diseases remain poorly understood, but he ignored this and instead compared the post-finasteride disability to “mystery syndromes.”

Attitudes & blind spots

Certain attitudes and beliefs run as an undercurrent through Trüeb’s articles on post-finasteride syndrome.

Dermatologist as guru; patient as meek disciple. Trüeb professed in three different articles: “The physician’s role is to help the patient figure out what he really wants and then to use the power of persuasion to show the patient the way there. At length, the way a physician phrases his recommendations can powerfully sway a patient’s choice and have an influence on the treatment outcome.”6 In Trüeb’s view, the doctor must deploy his special powers to sway the patient, who is dim and pliable. There are overtones of the doctor as both guru and Freudian analyst.

Dermatology is the premier specialty. Trüeb sniffs at research by “non-dermatologists.” Surely other disciplines would have something to contribute regarding effects of finasteride on the brain, eyes and other organs. But the Swiss doctor insists that hair and skin experts are best suited to rule on its safety. (This does not prevent his own forays into psychiatry.)

Medical hubris. Trüeb has likened post-finasteride syndrome to a delusional condition because it has not been explained “biologically.”6 Of course, there are many recognized diseases that are not well-understood, such as Parkinson’s disease, glioblastoma and lupus. For Trüeb, a disease is legitimate if a physician finds it plausible. The doctor holds a priestly role, with unique access to the truth.

Omission of social context. Even in a physician’s exam room, social factors are in play. Patients might be loath to speak about sexual dysfunction, panic and suicidal thoughts with a dermatologist. This could explain why Dr. Trüeb and his colleagues do not often hear about these side effects (however, when they write, “we have rarely observed depression or suicidality,” one wonders: how rarely, and why is this mentioned only in passing?7). Physicians may incorrectly assume that all patients are an open book, and that diagnostic tests are comprehensive. This creates a blind spot for medical concerns that are embarrassing or not easily observed.

Pro-drug, pro-status quo. Any challenge to the medical consensus is viewed with suspicion. Large clinical trials are taken at face value, despite questionable safety data from industry-sponsored trials.30,31 Patient concerns are put down to pre-existing conditions or psychological deficiencies. These articles assure us that the medical consensus is correct while the men complaining of post-finasteride syndrome are mad.

Reality test

Trüeb and colleagues have suggested that post-finasteride syndrome is a delusional disorder linked to a histrionic personality disorder, and that it resembles “mystery syndromes” with no biological basis.5 They have hedged their views throughout, using words such as “circumstantial” and “in our opinion.” The theory could be tested in a case-control study. Researchers could identify ten cases of post-finasteride syndrome and ten healthy controls who had previously taken finasteride for hair loss. All would receive a psychiatric evaluation. If patients in the first group were consistently diagnosed with delusional disorder and histrionic personality disorder, while healthy controls were not, it would lend support to Trüeb’s theory.

Trüeb did not once propose how his theory might be tested empirically. It rests only on speculation and free association, with no support in systematic research.

Conclusion

Trüeb maintains post-finasteride syndrome is a patchwork of mental problems involving delusions, a personality disorder and the nocebo effect. To arrive at this view, he started with a personal impression of a patient (“humorless and oversensitive”), linked it to misreadings of earlier research, free-associated, played up the grotesque, and passed off the whole package as research. Then he repeated and cited this view in later work, calling it “well-established.” There is in fact no proper argument and no grounding in evidence.

Dr. Trüeb is obviously fascinated by psychopathology, having authored a book chapter and multiple articles on the topic. Some of the earlier work seems informed and serious. But when post-finasteride syndrome came into view, the work became shrill and obsessed. Why? I surmise three reasons. To defend the profession’s status quo; scapegoat an uncooperative patient; and use the syndrome as a projection screen for his interests in psychopathology.

At the journal where the last four articles appeared, a co-Editor-in-Chief and an editorial board member have extensive ties with the pharmaceutical industry. Both have been advisors for Keeps, a prominent prescriber of finasteride for hair loss, since 2020, and had past involvement in Merck’s rollout of Propecia. Whether this background had any role in the publication of Trüeb’s articles is unknown.

Supplementary materials may be found in an appendix.

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