| Abstract|| |
Eighty male patients with AGA, not treated in the previous 6 months were enrolled in this randomized, double blind, placebo controlled trial to assess the safety and efficacy of finasteride, 1mg daily, on hair growth. Patients were randomized into 2 groups: Group 1 received 1 mg of finasteride daily and Group 2 received a placebo for a period of 12 months. Efficacy was assessed by hair counts, photographic records, patient's self-assessment questionnaire and clinical assessment. Safety was assessed by history taking and laboratory parameters.
A total of 39 patients completed the study. Finasteride was rated superior to placebo with respect to all efficacy measures. At the end of study, finasteride treated patients had a mean increase of 20.56±4.73 hairs compared to a decrease of 9.56±5.53 hairs in placebo treated patients. Photographically, 69.56% of finasteride treated patients were rated as improved at 12 months compared to only 6.25% of placebo treated patients. Ten (25%) of finasteride treated patients developed adverse effects (5-decreased libido as well as erectile dysfunction, 4-erectile dysfunction, 1-decreased libido).
Finasteride in comparison to placebo was effective in promoting hair growth in male patients of AGA. However, the side effects to the drug were high in this study.
Keywords: Finasteride, 5-a reductase inhibitor, a0 ndrogenetic alopecia, h0 air growth
|How to cite this article:|
Prasad H R, Khanna N, Pandhi R K. A randomized double blind study of the effect of finasteride on hair growth in male patients of androgenetic alopecia. Indian J Dermatol 2005;50:139-45
|How to cite this URL:|
Prasad H R, Khanna N, Pandhi R K. A randomized double blind study of the effect of finasteride on hair growth in male patients of androgenetic alopecia. Indian J Dermatol [serial online] 2005 [cited 2020 Aug 10];50:139-45. Available from: http://www.e-ijd.org/text.asp?2005/50/3/139/18927
| Introduction|| |
Androgenetic alopecia (AGA) is the commonest cause of hair loss. At least 50% of men by the age of 50 years and a similar proportion of women by the age of 60 years are affected by AGA.
Orentreich first proposed the term "androgenetic alopecia", because it combined the characteristic features of this condition, namely, a genetic predisposition to the effects of androgens resulting in hair loss. The genetic factors are not yet clearly understood. AGA is thought to result either from an autosomal dominant inheritance with increased penetrance in men or a multifactorial inheritance.
Dihydrotestosterone (DHT) is the active androgen in AGA. DHT is formed by action of 5a-reductase on testosterone (T) by two different isoenzymes: type 1 in sebaceous glands and type 2 in inner root sheath. It is thought that the type 2 isoenzyme is probably involved in the pathogenesis of male pattern hair loss. Levels of type 2 isoenzyme are higher in men than in women and higher in areas affected by AGA than in the occipital region. The DHT levels are also significantly higher in bald scalp in comparison to hair containing scalp, while there is no difference in mean T levels. The levels of androgen receptors are also higher in men than in women and greater in frontoparietal region than in occipital region, which is always spared by the disease. Male pseudohermaphrodites are deficient in type 2 5a- reductase, while the type 1 isoenzyme is normal. So these patients have no facial or body hair and they do not show temporal hair line recession or vertex balding, but they essentially have normal scalp hair.
Finasteride, a synthetic 4-azasteroid, is a specific inhibitor of 5a-reductase. It is a much more specific inhibitor of type 2 isoenzyme of 5a reductase than type 1 isoenzyme. It has no binding affinity for androgen receptors site and in itself has no androgenic or antiandrogenic properties. The efficacy of finasteride in the management of AGA has been proved by large multicentre trials., The adverse effects of finasteride are related to sexual function, mainly manifesting as decreased libido, erectile dysfunction and decreased ejaculatory volume.
This study was conducted to determine the efficacy and safety of finasteride on hair growth in male patients of AGA in India.
| Materials and methods|| |
A randomised, double blind, placebo controlled study, approved by the Ethics Committee of All India Institute of Medical Sciences (AIIMS) was conducted at the Department of Dermatology and Venereology, AIIMS, New Delhi, India. All patients gave a written, informed consent for induction in the trial.
A total of 80 male patients of AGA, attending the Dermatology and Venereology Out-patient Department at AIIMS were included in the study. All patients were in the age group of 21-40 years. Patients with mild to moderate hair loss (Norwood classification II, IIa, III, IIIa, IIIv, IV, IVa) were included while patients with type I or severe hair loss (V, Va, VI, VII) were excluded from the study. Other exclusion criteria were: history of sexual dysfunction, evidence of hepatic dysfunction and treatment with hair growth promoting agents within 6 months prior to inclusion in the study.
At the first visit, the particulars of the patients were noted and informed consent was obtained. A detailed medical and family history was recorded. The severity of hair loss was assessed using the Norwood classification. Routine investigations like blood cell counts, erythrocyte sedimentation rate, blood glucose levels and chest X-ray were done. Liver and renal function tests were done along with serum lipid profile and electrocardiogram in each patient. Clinical close up photographs of the scalp were taken. The patients were randomized into 2 groups:
Study group (Group 1) : Received 1mg, finasteride, orally for a period of 1 year;
Control group (Group 2) : Received a placebo for 1 year.
The need for regularity of treatment and follow up was emphasised. The patients were followed up for a period of 1 year at 3 monthly intervals.
The response to treatment was assessed by four methods.
a. Scalp hair counts in a 2 cm diameter circle.
b. Comparing pre-treatment and post-treatment photographs.
c. Patients self assessment by means of a questionnaire.
d. Clinical assessment by assessing changes in scalp hair.
a. Scalp hair counts: A circle of 2 cm diameter was selected at the edge of the receding hair line in the area of temporal recession. The distance of the centre of the circle from the line connecting both ears and from the midline was noted and recorded. The hair in the 2 cm diameter circle were clipped to a length of 2mm and the hairs with thick, black stumps representing terminal hairs were counted manually using a magnifying lens. The hair counts were done before starting treatment and repeated at 3 monthly intervals. The repeat hair counts were done from the same area and recorded.
b. Photographic assessment: Color photographs of the patients were taken showing 4 views of the patients' scalp hair: frontal, temporal, mid-pattern and vertex. The photographs were taken with a Nikon FM-10 camera using Kodak 35mm films. The photographs were taken at initiation of therapy and repeated at 3 monthly intervals. The photographs were assessed by a panel of 3 observers, who were blinded to the nature of treatment. The follow up photographs, in comparison to baseline photographs were assessed on a 7 point scale:
Excellent response: 3
Moderate response: 2
Minimal response: 1
No change: 0
Minimal worsening: -1
Moderate worsening: -2
Severe worsening: -3
c. Patients' self assessment: Self assessment of the efficacy and the adverse effects of the treatment was done through a self administered questionnaire of 6 items [Table - 1]. Of these 6 items, 4 were pertaining to the effect of treatment on hair growth and 2 related to the adverse effects of treatment. All the items were answered on a 7 point scale similar to the one used for assessing photographs.
d. Clinical assessment: The clinical response to treatment was assessed by examining the scalp for the density of terminal hairs at the edge of the receding hairline and for any new hair growth. The response was graded on 7 point scale similar to the one used for photographic assessment.
During follow up, complete blood counts, erythrocyte sedimentation rate, blood sugar, liver and renal function tests were done at 3 monthly intervals. Serum lipid profile was done at baseline, at 3 months and at completion of study.
The statistical analysis was done using SAS 8.0 statistical software. The primary hypothesis for hair counts was assessed by difference between the count at each point of time and the accompanying baseline count by means of paired t-test. The statistical difference between the 2 groups at each point of time for all efficacy measures including hair counts, photographic assessment, patient self assessment and clinical assessment was calculated by means of two sample t-test. A p-value of less than 0.05 was considered statistically significant.
| Results|| |
The patient profile has been summarised in [Table - 2]. Out of the total 80 patients, 6 withdrew from the study because of adverse effects. All the 6 patients were in finasteride treated group. Of the remaining 72 patients, only 39 completed the study, 23 in the finasteride group and 16 in the placebo group.
Evaluation of efficacy measures
a) Hair counts: Finasteride treatment produced progressive increase in hair counts at 3, 6, 9 and 12 months [Table - 3], whereas the placebo treated patients continued to lose hairs at 6, 9 and 12 months (all p values, <0.05 vis a vis baseline). At month 12, the study demonstrated an increase of 20.56±4.73 hairs (mean±SE) for finasteride and decrease of 9.56±5.53 hairs for placebo, with a net difference of 30.12±7.31 hairs between the two groups. At month 12, 87.5% of the patients treated with placebo had decreased hair counts in comparison to only 21.74% of the patients treated with finastende. Thus, finasteride was significantly superior to placebo in increasing the hair counts, the improvement starting as early as 3 months.
b) Photographic assessment: Analysis of the serial photographs [Figure - 1], [Figure - 2], [Figure - 3] showed that finasteride was superior to the placebo group at each point of time of follow up (all p values <0.05). At 12 months, 69.56% of the finasteride treated patients were rated as improved by means of photographs, while only 6.25% of patients on placebo were rated as improved.
c) Patient self assessment: The questionnaire analysis revealed that finasteride was superior to placebo; however the superiority of finasteride over placebo was not uniform for all the 4 questions pertaining to efficacy of treatment.
l Appearance of hair: Finasteride treated patients had statistically significant superior rating at 6,9 and 12 months (p value, <0.05) but at 3 months, the difference between the two groups was not statistically significant (p value, >0.05).
l Hair fall: Finasteride treated patients were significantly better rated at each point of follow-up (all p values, < 0.05).
l Hair growth: Finasteride treated patients had significantly better hair growth at 6, 9 and 12 months (p value, <0.05); however the difference in rating between the two groups was not statistically significant at 3 months (p value, >0.05).
l Bald areas: Reduction of the bald areas in finasteride treated patients was rated as significantly better at 6 and 12 months (p value, <0.05) while at 9 months, the response to the drug was not significantly superior to placebo. At 3 months, placebo was rated superior to finasteride, however it was not statistically significant.
At 12 months, the percentage of patients assessing themselves as improved for hair appearance were 60.86% in finasteride group and 18.75% in the placebo group. For hair fall, it was 73.9 1% versus 43.75%, for hair growth, it was 52.17% versus 12.5% and for bald area, it was 39.13% versus 18.75%, in the finasteride and placebo groups, respectively.
d) Clinical assessment: The clinical assessment of hair growth also revealed that finasteride was superior to placebo. The finasteride treated patients were rated superior to placebo at each point of follow-up, but it was significant only at 6, 9 and 12 months (p value, <0.05). At 12 months, 56.52% of patients in the finasteride group were assessed as improved, whereas in the placebo group only 18.75% were rated as improved.
Clinical parameters: Clinical adverse events that developed in each group are shown in [Table - 4]. Six (15%) patients from the finasteride group opted out of the study due to events, which the patients attributed to the drug. None of the patients from the placebo group withdrew from study due to any adverse event. All the 5 patients with both complications of erectile dysfunction and decreased libido opted out of the study and the adverse events subsided spontaneously in 15-20 days. Of the 4 patients only with erectile dysfunction 1 opted out of the study, 3 continued the treatment and in 2 of them the complaints subsided spontaneously.
Laboratory parameters: There were no abnormalities in complete blood counts, erythrocyte sedimentation rate, liver and renal function tests in any of the patients throughout the period of treatment. Serum lipid profile abnormalities were found in 3(7.5%) of placebo treated patients and 1(2.5%) of the finasteride treated patients after 12 months of treatment. The finasteride patient had raised serum triglycerides levels, while in the placebo group 2 patients had increased serum cholesterol levels and 1 had raised levels of both cholesterol and triglyceride. The rise was mild in all the cases.
| Discussion|| |
Hair is a major component of an individual's general appearance and loss of hair has negative symbolism. AGA is the commonest type of alopecia and a large number of modalities have been used for treatment of AGA. However, majority of these have been published as case reports of reversal of alopecia when these agents were used to treat other medical illness. Till recently, minoxidil was the only agent which was proved to be effective in male patients of AGA by many controlled clinical studies.-
The safety and efficacy of finasteride in AGA has been confirmed by multicentred, double-blind, placebo controlled studies., Unlike the previous studies, we did not restrict the study to assess any particular areas of baldness. The earlier studies had demonstrated the efficacy of finasteride in vertex and frontal baldness. In our study, patients were included according to the Norwood classification and finasteride produced significant improvement in the hair counts in the target area. There was a significant increase in the hair counts from baseline at each point of follow up. The increase in hair counts with finasteride was evident as early as 3 months and it progressed throughout the period of study. In contrast, the patients in the placebo group progressively lost hair, consistent with the natural history of AGA.
The previous studies of finasteride in AGA done by Kaufman et al  and Leyden et al assessed the hair counts at 0, 6 and 12 months and the finasteride treated patients had a significant increase in hair counts at 6 months. In this study the hair counts were assessed at 0, 3, 6, 9 and 12 months and a significant increase in hair counts with finasteride was evident at 3 months itself (p value <0.05). In comparison to the patients treated with placebo, finasteride treated patients had a net increase of 30.12 ± 7.31 hairs at 12 months in the target area.
In the blinded comparison of pre-treatment and post-treatment photographs, which assessed the change from baseline at each point of follow up, finasteride treatment produced progressive improvement in hair growth throughout the follow up period, whereas the placebo treated patients worsened over time. The same results were seen in both the earlier studies and in addition, in those patients who continued treatment for another year, these photographic improvements were maintained in the second year. In our study, it was observed that the major improvement was in the vertex views and mid-pattern views. But some improvement was also noticed in frontal and temporal views. The photographic assessment suggested that the treatment with finasteride in patients of AGA improved the overall appearance of hair.
The finasteride treated patients assessed themselves as significantly improved in comparison to the placebo treated patients for all the 4 questions. The patients rated their hair appearance as improved when treated with finasteride at 3 months, which progressed throughout the study. The same results were obtained for questions relating to change in hair fall and hair growth. But for changes in bald area, the finasteride treated patients assessed themselves as significantly improved at 6 and 12 months, but not at 3 and 9 months. This inconsistency in the results for this question could partly be due to the recall bias, as they assessed the change from baseline and this recall bias is typical of any patient questionnaire. This recall bias could have played its role for all the other questions also but was not so obvious in any of them. The placebo effect was evident in this study, especially with the question relating to changes in hair loss, with nearly 43.75% of placebo treated patients assessing their hair loss as improved.
Treatment with finasteride at doses as low as 0.2mg/day for 6weeks has been shown to maximally suppress scalp and serum DHT in balding men. However, in a clinical dose ranging studies of finasteride in AGA, it was found that 1mg/day is the optimal dose for treatment of men with AGA. In another study male patients of AGA in the age group of 53-76 years, who also had BPH were treated with finasteride, 5mg and it was found that the drug significantly increased mean hair counts in comparison to placebo, but this drug has not been found to be effective in postmenopausal women with AGA.
The present study has raised concerns about the safety of finasteride, with a total number of 10 (25%) finasteride treated patients developing adverse effects (1 decreased libido, 4 erectile dysfunction and 5 both erectile dysfunction and decreased libido). The earlier studies have reported a very small incidence of adverse events, 4.2% by Kaufman et al and 2% by Leyden et al . Finasteride in the dose of 5mg daily has been used to treat BPH for several years and is known to have an excellent safety profile. With 1 year of treatment with finasteride 5mg daily, decreased libido occurred in 3.3% versus 1.6% of placebo controls, impotence 3.7% versus 1.1% and ejaculatory disorders in 2.9% versus 1.1% respectively. When compared to the above findings, the rate of adverse events in the present study was very high. As a part of the informed consent, the side effects were explained to the patients and the increase in adverse effects may be due to psychological effects. However, this is an unlikely explanation, because none of the patients on placebo developed sexual function related adverse events. These adverse events subsided spontaneously in all those patients who withdrew from the study within a period of 15-20 days. These adverse effects are likely to resolve in many patients even with continuation of treatment, as was found in previous studies, but the patients in this study refused to continue the medication and withdrew from the study voluntarily. No other significant clinical or laboratory adverse events were observed. In addition to the above adverse events, finasteride may cause hypospadiasis and malformations of external genitalia in the developing male fetus when administered to pregnant women. Moreover in postmenopausal women with AGA, finasteride has not been found to be effective.
In summary, finasteride is effective in the management of AGA. The efficacy has been demonstrated by the significant increase in hair counts, serial photographic assessment, clinical and patient self-assessment. These beneficial effects were noticed as early as 3 months after starting the medication. Knowing the excellent safety profile of finasteride, the safety concerns raised by this study may be an abberation rather than a rule. However, these results emphasize the need for the informed consent prior to starting the therapy and careful follow-up for the adverse events.
| Acknowledgement|| |
We are grateful to ARISTO Pharmaceuticals Ltd., India for providing finasteride and placebo tablets for the study.
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[Figure - 1], [Figure - 2], [Figure - 3]
[Table - 1], [Table - 2], [Table - 3], [Table - 4]