Efficacy and Safety of Combined Topical 17α-Ethinyl Estradiol With Minoxidil vs Topical Minoxidil Alone in Patients With Female Pattern Hair Loss

We applaud the authors for publishing this valuable study focused on the use of minoxidil and estradiol for the treatment of alopecia, particularly for the transparent reporting of their methodology. Female pattern hair loss is challenging to treat, with topical minoxidil being the only FDA-approved medication for the disease. Recently, interest in off-label use of topical hormonal medications has been noted. In a study presented at the 2019 American Academy of Dermatology meeting, clascoterone (a dihydrotestosterone blocker) was noted to be more effective in increasing hair counts than cyproterone acetate or 17α-estradiol in patients with androgenetic alopecia. Furthermore, patients' interest in hormonal therapies may be peaking, with topical estrogen treatments for hair loss trending in the media. In this timely randomized controlled trial, the outcomes of treatment with topical minoxidil 2% (MX) versus a combination of 17α-estradiol 0.01% and minoxidil 2% (EMX) were assessed in patients with female pattern hair loss.

In summary, 22 patients in the EMX group and 21 patients in the MX group underwent daily topical treatment for 24 weeks. The outcomes that were assessed included hair density, fiber thickness, and follicular unit density. The authors reported no differences in improvement parameters between the two treatment groups; however, they noted that the study may have lacked statistical power owing to a small sample size. The authors noted a significant difference in the rate of side effects between the treatment groups, with 55% of the patients in the EMX group experiencing menstrual irregularities compared with 5% of those in the MX group. This finding was surprising, given that topical 17α-estradiol is frequently used for vaginal atrophy, with menstrual irregularities being an uncommon side effect despite being applied to a mucous membrane in those cases.

The field of hormone therapy is exciting, and this study touches on the continued need to investigate the use of estrogen products for the treatment of patients with hair loss. Traditionally, in hair loss studies, hair count locations are confirmed with a permanent tattoo on the scalp. It appears that tattoos were not utilized in this study. Of note, a 2% minoxidil solution was used in this study; however, for many clinicians, 5% minoxidil is the concentration of choice when treating female pattern hair loss. The authors alluded to future studies with a larger sample size as well as monitoring of serum estrogen levels. If this is done, it may be prudent to use a 5% minoxidil formulation.

In conclusion, this is a timely study, as topical estrogen products appear to be flooding the skin care marketplace. Despite the lack of a significant superiority of the combination treatment over minoxidil alone in this study, future studies on gonadocorticoid pharmaceuticals in female pattern hair loss would be welcomed.