Androgenetic alopecia which occurs in females is referred to as female pattern hair loss. The cause of androgenetic alopecia is hereditary hypersensitivity of the hair roots to the male hormone, testosterone. The severity of female pattern hair loss is milder than that of male pattern hair loss. Nonetheless, it has a tremendous effect on appearance, interferes with the social lives of patients, and may result in psychological pain. In addition, due to the aging of the population in general and the increasing number of women having a social life at an older age, the demand for a treatment for female pattern hair loss is rapidly increasing2-4
. Various therapeutics have been tried for the treatment of female pattern hair loss; however, treatment outcomes are not always satisfactory, and further studies for the development of new therapeutics are needed4
Until now, a variety of factors have been suggested as the cause of female pattern hair loss. It has been reported that thyroid diseases or a reduction in serum ferritin are associated with female pattern hair loss. It is thought that androgen plays the major role in female pattern hair loss11-13
. Several studies have reported that, in the hair follicles in the alopecia areas of androgenetic alopecia patients, 5α-reductase activity, DHT concentration and androgen receptors are elevated in comparison with the levels in normal individuals14-18
. Testosterone is converted to DHT by 5α-reductase, and due to the action of DHT, a reduction in the sizes of hair follicles and a shortening of the growth period occurs, causing further hair loss19
. In females, as compared to males, the expression of the 5α-reductase androgen receptor in the hair follicles in the frontal region is low, and P-450 aromatase, which converts testosterone to estradiol, is abundant. Thus, relative mild hair loss results in. However, it has been also reported that, even in female pattern hair loss patients, the concentrations of testosterone and serum dehydroepiandrosterone sulfate are higher than those in a normal control group20,21
The clinical trial drug used in our study, 0.025% Ell-Cranell® alphasolution, is a stereoisomer of the female hormone 17β-estradiol. Various experiments have shown that, in comparison with 17β-estradiol, 17α-estradiol did not exhibit estrogen activity or exhibited only very weak activity. In the treatment of androgenetic alopecia, the action mechanism of 17α-estradiol is to suppress 5α-reductase activity, which impedes the conversion of testosterone to the more potent metabolite DHT5,22,23
. In addition, it inhibits 17β-dehydrogenase activity, resulting in a slowing of the conversion process of androstenedione to testosterone. As a result, there is a reduction in the syntheses of testosterone and DHT6
. On the other hand, by stimulating aromatase, the conversion of testosterone to estradiol is accelerated, hence, testosterone is reduced. It thus acts to ultimately reduce DHT7
. In addition, it has been reported to accelerate the generation of hair follicular matrix cells8
The 0.025% Ell-Cranell® alpha solution has been used for the past 30 years in Europe and in South America. There were several reports about the therapeutic effects of 17α-estradiol in European population. In a controlled, randomized double-blind study, 63% of the treated patients with 17α-estradiol showed a reduction of the amount of telogen hairs, whereas in the control group the same reduction was found in only 37% of the cases23
. Wozel et al.22
reported that 17α-estradiol increases and maintains the rate of anagen hair in 88% of the treated patients. When compared with minoxidil 17α-estradiol showed relatively lower efficacy compared to minoxidil in hair density and thickness5
In our clinical trial, the subjects were female pattern hair loss patients between the ages of 18 and 55 years old who had been diagnosed with specific type F1 or F2 by the BASP classification, and the efficacy and safety of 0.025% Ell-Cranell® alphasolution were assessed9
. The results of our clinical trial, during which 0.025% Ell-Cranell® alphasolution was applied to female pattern hair loss patients for eight months, showed that, after four and eight months of applying the study drug, the increases in the number of hairs and the diameter of hair, as assessed by phototrichogram, were statistically significant. Specifically, at eight months after the drug application, the number of hairs increased by 31.57 (±34.63) hairs/cm2
(95% confidence level: 21.83, 41.31) in comparison with baseline.
Our clinical study was a single-arm study, and thus interpretation of the results may be somewhat limited in comparison with studies that compared results to a placebo control group. Nonetheless, the results are comparable to the increased number of hairs (26.7 hairs/cm2
) that was obtained after 32 weeks of applying 2% minoxidil in a double-blind, random assignment clinical study that was conducted previously in female androgenetic alopecia patients24
At two and eight months after starting the study drug, the responses to the statements 'the product smells good' and 'after using the product, my hair is difficult to comb', more patients responded 'no' compared to those with affirmative responses. In other categories ('it is easy to apply the product,' 'the time for skin absorption of the product is satisfactory,' 'the use of the product did not render hair or scalp oily,' 'the product did not render the scalp or hair sticky,' 'the product did not induce pruritus in the scalp,' 'the product does not induce a tingling sensation or scalp irritation,' 'the product did not leave residue on the scalp' and 'overall, the product could be applied easily') positive responses represented more than 60% of the total.
The results for the evaluation of hair loss and hair restoration effects at two, four, six and eight months after the start of drug application did not show consistent trends. Overall, hair loss and hair restoration effects were shown to be best at eight months, and the satisfaction levels of patients were shown to be similar at each time point. The change in perceived appearance due to hair loss and hair restoration improved more than 30%. However, the satisfaction level of patients was relatively low. This could be because while hair loss was relatively improved, it was not completely cured. As the treatment period increased in duration, the expectation level for improvement increased.
The results of the analysis of the overall evaluation performed by the investigators at two, four, six and eight months after the start of drug use show that, in comparison with 'no change' or 'worsened,' the percentage of the subjects who evaluated themselves as 'greatly/moderately/slightly improved' gradually increased, showing that improvements in the alopecia condition were observed with time. In addition, the results of the evaluation at four and eight months showed an increase in the number of hairs and the diameter of hair when assessed by phototrichogram.
The results of the safety evaluation showed that abnormal drug reactions associated with the experimental drug were detected in 3.84% of the subjects (2/52 patients, 5 cases). All were mild local reactions, and there were no dropouts due to serious abnormal reactions or abnormal reactions. In the evaluation of the previously reported abnormal reactions caused by 0.025% Ell-Cranell® alpha solution (erythema, tingling sensation, pruritus, desquamation) that was performed at two, four, six and eight months, none of the patients experienced pruritus or desquamation. After two months of drug application, mild erythema and a tingling sensation were detected in one subject each (1.92%). However, the reactions were not reported again after four, six or eight months of drug application. Therefore, in the androgenetic alopecia patients who applied 0.025% Ell-Cranell® alpha solution for eight months, no noticeable abnormal reactions or events that violate safety regulations were observed. In addition, the observed abnormal drug reactions were all topical reactions in the application area, and no systemic reactions were observed. In conclusion, in this clinical study, the efficacy and safety of 0.025% Ell-Cranell® alpha solution were thoroughly evaluated, and this drug is considered to be a safe alternative for the effective treatment of female pattern hair loss.