Researchers blamed growing safety concerns on patients, overlooking social context and weaknesses in safety regime
The official view of Propecia, fashioned by Merck at a reported cost of $450 million, is that the drug is safe and effective. Upon approval by FDA in 1997, this view was carried forward by dermatologists, some of whom were engaged by Merck as investigators, consultants, speakers and co-authors.
But as safety concerns have emerged over the last two decades, the slogan “safe and well-tolerated” has come under strain. Since 2010, studies have reported evidence of severe and lasting dysfunctions after discontinuation of finasteride. Other researchers have attacked these studies, calling them underpowered, lacking in controls, retrospective, plagued by confounding variables, and so on. As the pace of adverse event reports has increased over time, articles have questioned whether new reports are valid. Three strikingly similar papers advanced a raft of other explanations including advocacy group activities, social media use, mental illness, distress over hair loss, litigation, and relationship disappointments among other factors. (One co-author disclosed he had been retained as an expert for Merck’s defense in Propecia litigation, while another had been a consultant on a Merck trial which included finasteride.)
In directing attention away from the drug as a possible cause, researchers have overlooked social factors and weaknesses in the drug safety regime itself. A discussion of these factors follows.
Stigma. Unlike headaches and rashes, sexual dysfunction and mental health concerns carry social stigma. These topics lie outside the bounds of polite conversation. Patients may keep these concerns private in medical settings, out of embarrassment and a sense of propriety. This tendency would also have influenced adverse event reporting in clinical trials (playing to Merck’s advantage).
Events after discontinuation. If adverse events arise or worsen after discontinuing finasteride, the patient may no longer be seeing the physician. This would prevent expression of concerns to the prescribing physician. Even if they are reported, new or worsening concerns after stopping a drug may seem implausible. Despite increased attention to post-withdrawal conditions, these experiences strike many physicians and the general public as implausible.
Attribution. When a patient begins taking finasteride to stop hair loss, attention goes to the scalp and hair. If he later experiences sexual dysfunction, panic or suicidal ideation, the drug might not be an obvious culprit—especially if he is not aware of the mechanism of androgen inhibition. Sexual and neuropsychiatric events are internal and qualitative experiences—totally different in nature from the hair and scalp.
Specialization. Dermatologists are focused on hair and skin, typically without expertise in sexual medicine or neuropharmacology. Patients may feel it is inappropriate to discuss sexual or neuropsychiatric concerns with their dermatologist. In urology, erectile dysfunction in younger men is often assumed to be psychogenic. If lab tests show hormones in normal range, this might confirm the urologist’s suspicion of a psychogenic condition. Endocrinologists are also unlikely to find a diagnostic marker in lab tests. These specialties are not equipped to consider the impact of a drug across multiple systems and functions.
Medical hubris. Physicians tend to value diagnostic signs and the physician perspective over patient reports. They are typically trained to rule out diagnoses based on signs. Faced with an unfamiliar presentation without obvious signs, and perhaps lacking time or patience, the physician may conclude the patient’s concerns are merely psychological.
Concerns over liability. A patient reporting lasting harms of a drug may trigger fears of physician liability. As a result, physicians might draw attention away from the drug as a potential cause, and instead offer other explanations such as depression, concerns over hair loss, or use of social media.
Conflicts of interest. Certain prominent people in urology and dermatology participated in the development of Proscar and Propecia as investigators, consultants, co-authors and speakers. Their history of involvement, along with the specialties’ deep ties to industry, may influence the activities of societies, journals, conferences and teaching. Lending any credence to harms of a prescribed drug—particularly when litigation is pending—would not be well-received by drug makers. Societies are unlikely to bite the hand that feeds them.
Inadequate safety data. The quality of safety data from Merck’s clinical trials appears to be inadequate. The long history of label changes and adverse event reporting support this. (A warning of suicidal ideation and behavior was added to the U.S. label in July.) Patients have effectively been beta testers of a drug whose actual safety profile appears very different from information in Merck’s New Drug Application. Even today, the full extent of risks and harms of 5-alpha reductase inhibitors taken by young men is unknown.
Lack of research funding. There is little or no funding or interest in doing research on harms of prescription drugs; in fact, it may be a career risk, since it challenges the medical and regulatory status quo.
Increased volume of adverse event reports might not be an artifact, but a genuine and alarming signal which had previously been suppressed by a combination of factors. These include stigma and social boundaries, medical specialization, lack of diagnostic signs, and conflicts of interest among physicians. With increased awareness, patients have become attuned to the risks of finasteride and emboldened to express concerns. This long trend provides an opportunity to reflect on special challenges of detecting sexual and neuropsychiatric events, the need for greater attention to long-term drug harms and the ways in which industry ties can poison the doctor-patient relationship.