New reports based on patient questionnaires suggest finasteride (Propecia), used for male pattern baldness, leads to permanent — rather than temporary— sexual side effects. A closer examination reveals it is unclear, just yet, how common these long-term side effects are.
Finasteride (Propecia) has been approved for men with pattern baldness since 1998 with a relatively low side effect profile.1 Potential side effects include decreased libido and disturbed sexual function, but the majority of research shows that these sexual side effects are reversed when the drug is withdrawn.2,3
A number of new reports that are based on patient questionnaires suggest that the sexual side effects of finasteride may actually be permanent, and that the drug may also cause depressive symptoms and suicidal thoughts in patients who suffer from persistent sexual side effects.4,5 The studies have become a hot topic among dermatologists and other healthcare professionals who treat patients with hair loss, and it appears to be unclear, just yet, how widespread the issue of long-term sexual side effects is.
Questions about Scientific Accuracy
One of the most significant factors that has raised questions about the prevalence of long-term sexual side effects is that a clear-cut pattern for this link has not been extensively demonstrated in the literature.
“The one study that was recently published was not performed in a manner that could be repeated, did not follow men from the outset of taking the drug and only went by patient report,” explains Amy McMichael, MD, of the Center for Dermatology Research and the Department of Dermatology at Wake Forest School of Medicine in Winston-Salem, NC, in reference to the most recent articles that raised these questions.4,5 “None of the men had a pre-treatment survey regarding sexual side effects or depression, so it is difficult to compare this to an unknown baseline.”
Stephen E. Wolverton, MD, a professor of clinical dermatology in the Department of Dermatology at Indiana University School of Medicine, conducted a review of finasteride studies in order to determine the accuracy of the new studies reporting permanent sexual side effects and was not able to come to as definitive a conclusion. In particular, Dr. Wolverton looked at a study by McClellan and Markham (1999) that included nearly 1,900 men between 18 and 41 years of age randomized to either finasteride or placebo.3
According to Dr. Wolverton, the study by McClellan and Markham demonstrated that there was a slightly increased risk of sexual side effects in patients taking finasteride for male pattern baldness, including decreased libido, erectile dysfunction and ejaculation disorders, but, he adds, there are a couple of points in the article that are particularly important to the current debate about long-term side effects.
“One is that sexual adverse effects ‘resolved in many men who reported them but remained on therapy and in all men who discontinued therapy because of these adverse events,’”3 explains Dr. Wolverton. “So, in other words, things in any of those three categories went back to normal, even while they were still taking the drug. The other statement was that sexual adverse events resolved ‘in all men who discontinued therapy because of these adverse events.’”3
The body of literature on finasteride does consistently support the existence of sexual side effects that begin while patients are on the drug, but the reports also demonstrate that, for the most part, these side effects resolve either when the drug is withdrawn or over time as therapy continues. In a report from the Finasteride Male Pattern Hair Loss Study Group, a slightly higher proportion of finasteride users compared to patients on placebo reported drug-related adverse events (AEs) that related to sexual function, but only 11 men (1.4%) treated with finasteride and 8 men (1.0%) treated with placebo discontinued the study due to these side effects.6 In addition, the side effects resolved in patients who discontinued finasteride and in most patients who reported them but remained on the drug.6 Another study published in the Journal of the American Academy of Dermatology (JAAD) concluded that no adverse events were seen significantly more often with finasteride compared to placebo.7 This study in JAAD also demonstrated that the side effects cleared in men who stopped taking finasteride and in most men who remained on the drug.7
So, while the literature shows that most patients see a decrease in, or resolution of, sexual side effects as therapy continues or when the drug is stopped, there is potentially a slight risk of more long-term issues, and newer research demonstrates that this issue may be more problematic than previously thought.
Changes to Finasteride Labeling by The FDA
In April 2012, the FDA changed the professional labels for Propecia (finasteride 1 mg) and Proscar (finasteride 5 mg).8 The new labeling now states, under Adverse Reactions - Postmarketing Experience: “Reproductive System: Sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders; male infertility and/or poor seminal quality (normalization or improvement of seminal quality has been reported after discontinuation of finasteride).”8
According to Dr. Edwin Epstein, chairman of the International Society of Hair Restoration Surgery (ISHRS) Task Force on the finasteride controversy, this is the most important fact to convey to patients: That it is not fully understood yet if finasteride leads to permanent sexual side effects. Dr. Epstein encourages physicians who treat hair loss to be thorough in their explanation to patients in regard to the lack of definitive, consistent evidence for the risk of permanent sexual dysfunction with finasteride.
The ISHRS, of which Dr. Epstein is a past president (2009-2010), agrees with the FDA “that a clear causal link between finasteride and persistent adverse events has not been established.” The ISHRS also notes that the FDA labeling changes for Propecia and Proscar were “based on a review of 421 post-marketing cases from 1998-2011, or about 7 million patient years of drug exposure, of which 59 reported persistent sexual dysfunction.”
“The ISHRS position is that there is insufficient information to establish a cause: effect relationship, and the clinical experience of our members does not support this relationship,” explains Dr. Epstein.
By being transparent about the possibility of these long-term side effects, physicians can ensure that patients are fully informed, and patients will be empowered to make more educated decisions about treatment. The ISHRS also encourages transparency, recommending that all members discuss the risks and benefits of finasteride with patients.
“The primary concern of the ISHRS is for the health and welfare of our patients, and any potential adverse events related to finasteride need further investigation,” Dr. Epstein continues, noting that the ISHRS plans to inform its members and the general public of these changes by the FDA with an amendment to the finasteride position statement on their website. “We are committed to working with other medical societies and their physicians to gather more information on this controversy.”
The role the media plays in publicizing studies and the inability of patients to fully comprehend what the studies are saying are both factors that may relate to why the topic gained such widespread attention. The sensitivity of the side effects and the possibility of lawsuits may have also impacted the level of attention the issue received, experts added.
A study in the Journal of Sexual Medicine examined the prevalence of sexual dysfunction in patients taking finasteride. One hundred twenty patients with a clinical diagnosis of benign prostatic hyperplasia (BPH), who were sexually active and with an International Index of Erectile Function-erectile function (IIEF-EF) domain ≥25 were randomized to receive finasteride 5 mg, which they were told was an “X compound of proven efficacy for the treatment of BPH” for 1 year with (Group 2) or without (Group 1) counseling on the drug’s possible sexual side effect. Group 2 was informed that “. . . it may cause erectile dysfunction, decreased libido, problems of ejaculation but these are uncommon”9 In this study, blind administration of the drug “was associated with a significantly higher proportion of sexual dysfunction in patients informed on sexual side effects (Group 2) as compared to those in which the same information was omitted (Group 1) (P=0.03).”9 The researchers believe a similar scenario “is likely to occur in clinical practice, where the patient is counseled by the physician and has access to the drug information sheet.”9 In addition, they describe a ‘nocebo effect’ — an adverse side effect that is not a direct result of the specific pharmacological action of the drug — and suggest that this “has to be taken into account when managing finasteride sexual side effects.”9
“The media, of course, will focus on what sells the news, but scienctific studies attempt to minimize bias — you can’t help too much what happens when the media get a hold of data, but it can, at least, be presented accurately at first,” explains Dr. Wolverton. “So, the punch line on this is — if enough people hear that there might be a problem – analogous to Group 2 in the Mondaini study — then there’s a pretty good chance that they’ll experience that bigger side effect.”9
In conjunction with the sensitive nature of the side effects, the recent $18 million Accutane settlement may be a parallel for the finasteride controversy, where patients hear that a drug causes a side effect and that there is a possible financial gain. Dr. Wolverton describes this scenario as “the medical-legal cart getting ahead of the scientific horse.” In addition, the studies that have been called into question collected data from the website www.propeciahelp.com, which may have created a pool of participants who, Dr. Wolverton explains, “at least believe persistent sexual side effects are due to finasteride.”
In the ISHRS statement on the adverse events controversy, the group writes: “Reports of persistent sexual side effects have come from a variety of sources, with some Internet sites attracting individuals claiming to have sexual and psychological issues related to finasteride. While continued difficulty having erections after discontinuing finasteride has been reported in post-marketing surveillance the incidence of this problem remains unknown. This rare side effect is included in Merck’s patient product information in the United States, and in Public Assessment Reports of the Medicines and Health Regulatory Agency of the United Kingdom and the Medical Products Agency of Sweden.”
Dr. McMichael agrees this new evidence for long-term sexual side effects with finasteride has raised some intriguing — and complicated — questions.
“It is very interesting that patients are coming out now with this complaint, since the large pivotal trials that were required by the FDA did not reveal these findings,” she explains.
The Bottom Line
The reexamination of the sexual side effects of finasteride and the potential for a long-term impact that has occurred in light of these new studies seems to be yielding the same results as the studies that were first conducted to achieve FDA approval: The drug is a safe, well-tolerated, effective option for male pattern baldness.
“If you go back before the hype and look at the data, as with the McLellan study — basically, in 1999, when they did all the trials before this subject was tainted by the media or medical-legal incentives — the problem of persistent sexual side effects didn’t exist,” explains Dr. Wolverton. “There were transient sexual side effects, yes, but even the percentage of these transient side effects was small.”
However, the labeling changes were announced in conjunction with advice from the administration on how to counsel patients with hair loss who are considering treatment with finasteride.
“Despite the fact that clear causal links between finasteride (Propecia and Proscar) and sexual adverse events have NOT been established, the cases suggest a broader range of adverse effects than previously reported in patients taking these drugs. Information about these adverse events may be important to individual patients. Therefore, prescribers and patients need to be aware of them, as part of a discussion of risk and benefits of finasteride when determining the best treatment options.”8