Cyproterone

Abstract

Dihydrotestosterone is the main molecule responsible for androgenic alopecia. Finasteride, which reduces transformation of testosterone into dihydrotestosterone and decreases dihydrotestosterone activity, is approved for treatment of androgenic alopecia in men. We describe the case of a 46-year-old woman with androgenic alopecia, non-responsive to minoxidil, who initially benefited from finasteride. Due to only limited improvement after finasteride and persisting profound psychological distress resulting from androgenic alopecia, another 5-reductase inhibitor, dutasteride, was introduced. Clinical evaluation and trichogram were applied for assessment of dutasteride efficacy in this patient. Additionally, mean hair diameter was monitored by means of computer dermoscopy. After 6 months of therapy, significant improvement was observed and after 9 months the clinical diagnosis of androgenic alopecia could no longer be made in this patient. No side effects were observed. In conclusion, theoretical data and our experience in this case show that dutasteride might develop into a true alternative in treatment of androgenic alopecia.

Introduction

It is universally accepted that dihydrotestosterone (DHT) is responsible for androgenic alopecia (AGA) in men and women. (1-3) DHT induces miniaturization of hair and hair follicles by accelerating the mitotic rate of the matrix, by shortening hair cycle and increasing telogen shedding, as well as by increasing the duration of the lag phase or ketogen. (1,2) Thus, attempts have been made to reduce DHT activity in patients with androgenic alopecia by applying inhibitors of the enzyme 5-reductase, which transforms testosterone into dihydrotestosterone (DHT). Finasteride, an inhibitor of 5-reductase type 2 isoenzyme is now widely used for treatment of AGA in men. Also, the use of finasteride for AGA in women is increasingly gaining interest. (1,2)

Dutasteride is another 5-reductase inhibitor. It has the capability of inhibiting both isoenzymes, type 1 and type 2 of 5-reductase, and induces an even more significant reduction of serum DHT. (1) This molecule, however, has not yet been used for management of AGA.

Case Report

We describe a 46-year-old woman, who suffered from gradually progressive, diffuse loss of hair over the vertex and slow recession of the frontal hairline from the age of 39. Trichogram results, summarized in Figure 1, showed the presence of 44% telogen hair with an anagen/telogen ratio of 0.84/1. Histopathology from two sites showed partly fibrous root sheath remnants below miniaturized follicles with no perifollicular infiltrates, which confirmed the diagnosis of AGA. Dermoscopy of the affected scalp also revealed characteristic features of AGA, including variable hair diameter and hair miniaturization with a mean diameter of hair below 0.04 mm at the vertex and the front line area, as compared to 0.08 mm at the occipital area. The method of hair diameter assessment is presented in Figure 2. Dermoscopy also showed that follicle density at the vertex was 150 per square centimeter, which is significantly below normal values ranging from 300 to 400.

All basic laboratory data, including serum levels of dehydroepiandrosterone sulfate, androstedione and free testosterone were within normal range. From the age of 43 the patient received cyproterone acetate and ethinyl estradiol for contraception. According to anamnesis the treatment had no effect on disease progression.

The patient received topical 2% minoxidil therapy twice daily for 4 months with no improvement. Also, no improvement could be observed after introduction of 5% minoxidil twice daily for the next 2 months. The disease progressed and at this point the diagnosis of AGA type II/III according to Ludwig classification (1) could be made. Due to the lack of response and based on our previous positive experience in other female patients (unpublished data), as well as available literature (6,7) finasteride at the dose of 1 mg per day was introduced. After 3 months of therapy slow improvement could be noticed. Clinical picture and patient's satisfaction were slightly improved. As shown in Figure 1, this improvement was accompanied by changes in trichogram. Despite treatment continuation for another 3 months, no further improvement could be observed thereafter. At this point, the diagnosis of AGA type I/II according to Ludwig classification could be made.

[FIGURE 1 OMITTED]

Despite some improvement as compared to values upon introduction of treatment, the patient still experienced profound anxieties and distress due to persistent AGA and awaited further improvement.

Due to the lack of further improvement, finasteride was discontinued and another 5-[alpha] reductase inhibitor, dutasteride, at the dose of 0.5 mg per day was introduced. The patient received no other treatment either for AGA or for any other condition, accept continuation of cyproterone acetate and ethinyl estradiol for contraceptive purposes.

[FIGURE 2 OMITTED]

After 6 months of treatment an improvement in clinical picture, trichogram, hair diameter, and follicle density could be observed. After a total of 12 months of dutasteride therapy, the clinical diagnosis of AGA could no longer be made in this patient and trichogram values returned to normal. At dermoscopy, hair appeared thicker (with a mean of 0.073 in the vertex area and 0.065 at hair front line) and the initial significant variability in hair diameter was not observed. After a total of 12 months, dutasteride was discontinued and the patient remains free of AGA symptoms for several weeks after discontinuation.

No side effects were observed in this patient on either finasteride or dutasteride. Pregnancy was excluded prior to starting therapy. For both finasteride and dutasteride, the patient signed a consent form, which especially exposed the issue of teratogenicity and the need for effective contraception, despite the patient's repeated reassurance that she was single and there was no possibility of pregnancy.

Discussion

Finasteride, (1,2) an inhibitor of 5-[alpha] reductase type 2 isoenzyme, is now widely approved for the treatment of androgenic alopecia in men. Also, despite initial negative experience, there is increasing evidence of clinical efficacy of finasteride in female patients. (6,7)

Dutasteride is another inhibitor of 5-[alpha] reductase. There is strong theoretical basis for the hypothesis that potential efficacy of dutasteride in AGA might be even more pronounced, as compared to finasteride. This hypothesis is based on the observation that finasteride, a selective inhibitor of the type 2 isoenzyme of 5-[alpha] reductase, has the capability of reducing serum DHT by about 70%, while dutasteride inhibits both isoenzymes, type 1 and 2, and induces a 94% to 98% reduction of serum DHT. (8) This might lead to the conclusion that dutasteride has the ability of significantly inhibiting the effect of dihydrotestosterone on hair follicles and, as a result, reverse hair miniaturization in AGA. Based on these theoretical data, dutasteride was introduced in our AGA patient. Significant clinical improvement, accompanied by normalization of trichogram results, reduction in hair diameter variability, and an increase in mean hair diameter in affected areas was observed.

[FIGURE 3 OMITTED]

[FIGURE 4 OMITTED]

Dutasteride is presently approved in some countries, including USA, for symptomatic benign prostatic hyperplasia in men. Side effects, such as erectile dysfunction, decreased libido, gynecomastia, and ejaculation disorders have been observed in male patients receiving the drug. (1) No other side effects have been described in patients receiving dutasteride. Also, side effects in female patients are not known, but some clinical trials are still ongoing. In our patient, we have not observed any side effects during treatment. The patient's depression improved significantly, but we consider this to be the effect of aesthetic satisfaction rather than a direct effect of dutasteride.

The durability of improvement and the reproducibility of the therapeutic effect in other patients remain unanswered questions. It can be suspected that dutasteride will cause temporary improvement and decrease the speed of AGA development, but repeated or ongoing therapy for many years might be necessary, as is the case for finasteride in male AGA.

In our patient, computer dermoscopy (videodermoscopy) (1) was applied for evaluation of scalp hair in addition to traditional methods. The method enables visualization of hair miniaturization, as well as enabling the monitoring of degree of hair diameter variation, which is typical of androgenic alopecia in women. (1) The method is especially valuable for noninvasive measurement of hair diameter, which has been shown to be below normal range of 0,055-0,085 in patients with AGA. Thus, application of dermoscopy enables quantitative monitoring of therapy results in patients with AGA. To our knowledge this is the first description of the use of computer dermoscopy in trichology. We believe that dermoscopy may develop into a valuable tool in differential diagnosis and monitoring of hair loss. However, time is needed to develop strict quantitative criteria for evaluation of specific features found in various trichologic conditions.

In conclusion, theoretical data and our experience in this case show that dutasteride might develop into a true alternative treatment in androgenic alopecia. We have also shown that videodermoscopy is a valuable tool for evaluation of hair diameter in patients with AGA.

References

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10. Burkhart CG, Burkhart CN. 5 alpha-reductase and finasteride in pattern alopecia and acne. J Drugs Dermatol. 2004;3(4):363-364.

11. Libecco JF, Bergfeld WF. Finasteride in the treatment of alopecia. Expert Opin Pharmacother. 2004;5:933-940.

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Address for Correspondence

Malgorzata Olszewska MD PhD

Dept. Dermatology

Warsaw Medical School

Koszykowa 82

02-008 Warsaw, Poland

Phone: +48228242200

Fax: +48228242200

e-mail: malgorzataolszewska@yahoo.com

Malgorzata Olszewska MD, (a) Lidia Rudnicka MD (b)

a. Department of Dermatology, Warsaw Medical School, Warsaw, Poland

b. Department of Dermatology, CSK MSWiA, Warsaw, Poland

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