Efficacy of Topical Finasteride 0.5% vs 17α-Estradiol 0.05% in the Treatment of Postmenopausal Female Pattern Hair Loss: A Retrospective, Single-Blind Study of 119 Patients

Background and Objectives Female pattern hair loss (FPHL) is a common form of scalp hair loss that occurs in 38% of females. Currently, minoxidil solution is the only therapy approved by the US Food and Drug Administration, but many other treatments are used, including cyproterone acetate, spironolactone, topical 17α-estradiol, and prostaglandin analogs. Systemic finasteride has been considered a treatment option in women even though its teratogenic effects tend to limit its prescription. Recently, topical finasteride has been evaluated to limit the side effect profile of the drug. The objective of the present study is to compare retrospectively the efficacy of topical 0.05% 17α-estradiol solution and a 0.5% finasteride lotion in the treatment of FPHL. Patients and Methods We enrolled 119 postmenopausal female patients. The first group comprised 69 women treated with finasteride 0.5% and minoxidil 2%. The second group included 50 women treated with 17α-estradiol 0.05% and minoxidil 2%. At baseline and at 6- and 12- to 18-month follow-up, global photographs were systematically taken. Three operators blind to the prescribed treatment evaluated photographs using a 7-point scale. One-way analysis of variance and unpaired Student t tests were performed to analyze 7-point scale scores. Results The improvement was statistically significant from 6 months to 12–18 months, both for finasteride (P < 0.005) and 17α-estradiol (P < 0.05). The efficacy of topical finasteride was significantly greater than that of 17α-estradiol solution, both at the 6-month (P < 0.05) and at the 12- to 18-month follow-up (P < 0.005). In general, the highest improvement was observed after 12–18 months of treatment with topical finasteride therapy. Conclusions Topical finasteride 0.5% in combination with minoxidil 2% could represent a valid therapeutic option for the treatment of postmenopausal FPHL, showing higher efficacy than topical 17α-estradiol with minoxidil 2% both at 6-month and 12- to 18-month follow-up.

All patients were instructed to apply 1 mL of the assigned topical solution every night, on the vertex and frontal mineral supplements, and prostaglandin analogs, as well as surgical therapy and light therapy [10]. The weak estrogen 17α-estradiol has been used for many years as a 0.25-mg/mL topical alternative for the treatment of both male androgenetic alopecia and FPHL given the absence of feminizing estrogenic activity [11] and its ability to weakly inhibit 5α-reductase.
The objective of the present study was to compare retrospectively the efficacy of a topical 0.05% 17α-estradiol solution and a 0.5% finasteride lotion in the treatment of FPHL.

Methods
We performed an observational retro-

Introduction
Female pattern hair loss (FPHL), once known as female androgenetic alopecia, is a common form of nonscarring scalp hair loss in women occurring in 38% of women between the ages of 50 and 70 years [1,2]. It is characterized by a progressive miniaturization of hair follicles especially localized in the frontal, central, and parietal regions of the scalp [3].
The pathophysiology of FPHL is still not completely clear. Even though genetic and hormonal factors are considered involved as in the more common male form [4], its link to androgen hormones is less clear as it has been shown to appear in females affected by complete androgen insensitivity syndrome [5]. and European Medicines Agency for the treatment of male androgenetic alopecia are topical 2% and 5% minoxidil and oral finasteride (1 mg/day) [6]. Currently, minoxidil solution is the only FDA-approved therapeutic option for FPHL. Finasteride is a selective type II 5α-reductase inhibitor, the enzyme responsible for the conversion of testosterone (T) to its more active form dihydrotestosterone (DHT). It has been considered a treatment option also in women even though its teratogenic effects tend to limit its prescription. Reports of its efficacy in women are contradictory, with less consistent results than in men [7,8]. Recently, topical formulations have been evaluated to limit the side effect profile of the drug [9]. Other commonly used therapies in FPHL are cyproterone acetate, spironolactone, flutamide, topical 17α-estradiol, greater than that of 17α-estradiol solution, both at the 6-month (P < 0.05) and at the 12-to 18-month follow-up (P < 0.005). In general, the highest improvement was observed after 12-18 months of treatment with topical finasteride therapy.

Conclusions:
Topical finasteride 0.5% in combination with minoxidil 2% could represent a valid therapeutic option for the treatment of postmenopausal FPHL, showing higher efficacy than topical 17α-estradiol with minoxidil 2% both at 6-month and 12-to 18-month follow-up.

Statistical Analyses
One-way analysis of variance and   formulations (Figures 1-3). More important, the efficacy of topical finasteride (treatment 1) was significantly greater than that of the 17α-estradiol solution (treatment 2), both at the 6-month (P < 0.05) and at the 12-to 18-month follow-up (P < 0.005) (Figure 4). In general, the highest improvement was observed after 12-18 months of treatment with topical finasteride and minoxidil therapy ( Figure 5).

Discussion
In our work, we compared 2 galenic formulations for the treatment of FPHL. Minoxidil is a piperidinopyrimidine derivative and its action is believed to be due to its vasodilator properties. This is realized through the opening of potassium channels localized on the smooth muscular cells of the peripheral artery [14]. Approved in 1979 for hypertension, it is largely used as a topical product for alopecia owing to its common adverse effect of inducing hair growth. induces hair growth [16].   Currently, minoxidil is the only FDA-approved therapeutic option for FPHL [17]. The 2% concentration was approved in 1991, and 5% minoxidil was approved in 2014 [18].
Systemic finasteride inhibits the type II 5α-reductase, which normally catalyzes the conversion of testosterone  This is a stereoisomer of the female hormone 17β-estradiol, which weakly inhibits 5α-reductase. Furthermore, it suppresses the 17β-dehydrogenase, causing a reductive conversion of androstenedione to T, and it stimulates the aromatase, which induces the conversion of T to estradiol [21].
In our work, through global photographs and using the 7-point rating scale, we observed that both galenic formulations determined a statistically significant improvement of hair loss from 6-month follow-up to 12-to 18-month follow-up. More important, 0.5% finasteride showed higher efficacy than 0.05% 17α-estradiol lotion, both at 6 and 12-18 months. This outcome was statistically significant.
I t i s i n t e r e s t i n g t h a t f i n a steride-treated patients had an improvement at 6 months, which was com-