Reference: JAMA Dermatol. 2024 Apr 10:e240284
Practice Point: When treating androgenic alopecia, consider oral minoxidil in selected patients.
EBM Pearl: Head-to-head comparison trials don’t replace placebo-controlled trials, but may inform treatment choice and reveal helpful real-life information.
Androgenic alopecia (more commonly called male-pattern baldness) isn’t an earth shattering problem to have, but in a society that places an extremely high value on youth and appearance, it can be important. We didn’t have to comb through the literature too hard to find a study on management of this problem, but we did brush up on the pros and cons of head-to-head trials when reviewing this study published in JAMA Dermatology last month and funded by the Brazilian Dermatology Society. The researchers sought to compare the use of oral and topical minoxidil side-by-side, so they conducted a randomized double-blind trial.
Ninety men with androgenic alopecia between the ages of 18-55 were enrolled, of whom 68 were randomized to either: a) placebo tablets at bedtime and 5% minoxidil solution bid or b) minoxidil 5 mg tablets with placebo solution. All the patients who participated had small positional tattoos placed on their scalp as an objective assessment of hair loss. This method of counting hairs in the region of the tattoos is well described and seems very objective. This objective measurement, along with an overall subjective assessment of improvement, were both evaluated six months into treatment, along with measurement of blood pressure and information about potential adverse effects.
The overall conclusions: taking minoxidil by mouth once at night or applying it to the scalp twice a day is roughly the same for effectiveness, with more people taking the pill having headaches or hypertrichosis (hair where they don’t want it), and those using the solution having more itching or skin irritation. However, the authors state: "All patients were analyzed using the intention-to-treat principle at 24 weeks regardless of treatment adherence. Patients who discontinued treatment or were missing data (i.e., dropouts) were not included in the final efficacy analysis." We aren’t certain if something was lost in translation, but we believe this actually means that they analyzed this “per protocol.” A per-protocol analysis in a superiority trial risks disruption of the prognostic equivalence of the randomized groups and tends to overestimate the magnitude of effect of the study intervention. Ironically, since no additional benefit was found for oral minoxidil when the magnitude of effect may have been overestimated with a per-protocol analysis, this unforced error strengthens their conclusion that oral minoxidil is not superior to topical. (We’ve said this at least twice this year already but it’s worth saying again: analyze superiority trials with intention-to-treat methods and non-inferiority trials with per-protocol methods.)
A couple of quick thoughts. Efficacy in a trial setting doesn’t mean real-world effectiveness. Patient preferences about medication administration (a tablet once a day versus solution twice a day) and adverse effects (headaches versus local itching and irritation) are personal. Since this is essentially a cosmetic problem, effectiveness is going to depend a lot on cost—roughly equal—and tolerance of side effects. Also, you might ask yourself why we don’t see more head-to-head research comparing two different treatment options. After all, it’s probably not ethical to have a placebo arm when studying the treatment of cancer or another life threatening problem. But, one of the primary problems is economic: when comparing drug A and drug B, there is something of a zero sum game. This seems to have resulted in a "publication bias" in which head-to-head studies sponsored by pharmaceutical companies almost always have results favoring the sponsor’s product. While this isn’t shocking, it has given head-to-head studies a less than savory reputation. That’s a shame, as this publication shows that small numbers can yield interesting results.
For more information, see the topic Androgenetic Alopecia in Men in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, MPH, FACP, Deputy Editor at DynaMed. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Medical Editor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.