Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia. J Am Acad Dermatol 43:

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/12275255 Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia. J Am Acad Dermatol 43: 768-776 Article in Journal of the American Academy of Dermatology December 2000 Impact Factor: 4.45 DOI: 10.1067/mjd.2000.107953 Source: PubMed CITATIONS 153 READS 87 14 authors, including: Vera H Price University of California, San Francisco 167 PUBLICATIONS 4,951 CITATIONS Maria Hordinsky University of Minnesota Twin Cities 140 PUBLICATIONS 3,933 CITATIONS SEE PROFILE SEE PROFILE Wilma F Bergfeld Cleveland Clinic 355 PUBLICATIONS 5,024 CITATIONS David A Whiting 48 PUBLICATIONS 1,968 CITATIONS SEE PROFILE SEE PROFILE All in-text references underlined in blue are linked to publications on ResearchGate, letting you access and read them immediately. Available from: Maria Hordinsky Retrieved on: 09 May 2016

Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia Vera H. Price, MD, FRCPC, a Janet L. Roberts, MD, b Maria Hordinsky, MD, c Elise A. Olsen, MD, d Ronald Savin, MD, e Wilma Bergfeld, MD, f Virginia Fiedler, MD, g Anne Lucky, MD, h David A. Whiting, MD, i Frances Pappas, BA, MS, j Jennifer Culbertson, BA, j Paul Kotey, PhD, j Alan Meehan, PhD, j and Joanne Waldstreicher, MD j San Francisco, California; Portland, Oregon; Minneapolis, Minnesota; Durham, North Carolina; New Haven, Connecticut; Cleveland and Cincinnati, Ohio; Chicago, Illinois; Dallas, Texas; and Rahway, New Jersey Background: Finasteride, an inhibitor of type 2 5α-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. Objective: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. Methods: In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. Results: After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. Conclusion: In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning. (J Am Acad Dermatol 2000;43:768-76.) From the University of California, San Francisco a ; Northwest Cutaneous Research Specialists, Portland b ; University of Minnesota, Minneapolis c ; Duke University Medical Center, Durham d ; Yale School of Medicine, New Haven e ; Cleveland Clinic Foundation f ; University of Illinois, Chicago g ; Dermatology Research Associates, Cincinnati h ; University of Texas, Dallas i ; and Merck Research Laboratories, Rahway. j Supported by Merck Research Laboratories. Accepted for publication April 13, 2000. A preliminary report of the findings from this study was presented at the Hair Workshop, Brussels, Belgium, May 1998. Reprint requests: Joanne Waldstreicher, MD, Merck Research Laboratories, RY33-508, 126 East Lincoln Ave, Rahway, NJ 07065-0900. Copyright 2000 by the American Academy of Dermatology, Inc. 0190-9622/2000/$12.00 + 0 16/1/107953 doi:10.1067/mjd.2000.107953 In women and men who are genetically predisposed to androgenetic alopecia (AGA) or common hereditary hair thinning, androgens gradually transform large scalp hair follicles to small miniaturized hair follicles. 1,2 This transformation occurs over many hair cycles and represents shortening of the anagen growth phase and reduction in hair matrix size. The smaller follicles produce progressively shorter, finer, miniaturized hairs, which Abbreviations used: AGA: ANOVA: DHEAS: DHT: FSH: androgenetic alopecia analysis of variance dehydroepiandrosterone sulfate dihydrotestosterone follicle-stimulating hormone 768

J AM ACAD DERMATOL VOLUME 43, NUMBER 5 Price et al 769 ultimately do not cover the scalp effectively. In women, the thinning may be diffuse, but is generally greatest in the frontal/parietal region, with the frontal hairline being characteristically retained. 2-4 Dihydrotestosterone (DHT), the primary androgen implicated in the pathogenesis of AGA, 5 is formed by the peripheral conversion of testosterone by the enzyme 5α-reductase. There are two isoforms of human 5α-reductase, types 1 and 2. The type 1 isozyme is found in the liver, sebaceous glands, and possibly the infrainfundibular region of scalp hair follicles. 6-11 Type 2 5α-reductase is found in the prostate, male genitalia, root sheaths of hair follicles, and liver. 6-11 Men born with a genetic deficiency of type 2 5α-reductase do not develop AGA. 12-15 In addition, it has been shown that balding scalp skin contains increased type 2 5α-reductase and increased DHT levels. 16,17 These observations provided a rationale for the use of a type 2 5α-reductase inhibitor in the treatment of AGA in men. Finasteride is an orally active, specific inhibitor of type 2 5α-reductase. It has no androgenic, antiandrogenic, estrogenic, antiestrogenic, or progestational effects, no affinity for the androgen receptor, and it does not affect the physiologic actions of testosterone. 18-21 Large clinical studies in men aged 18 to 41 years with mild to moderate AGA demonstrated that finasteride 1 mg/day increased hair growth and slowed the progression of hair loss in most men. 22,23 In women, the underlying pathophysiology of AGA or hereditary hair thinning is believed to be similar to that in men. 2 The milder and somewhat less patterned manifestation of this trait in women may be due in part to differences in the relative levels of 5α-reductase, aromatase, and androgen receptors in scalp hair follicles in women compared with those in men. 24 The purpose of this study was to evaluate the efficacy of finasteride in increasing hair growth and in slowing the progression of hair loss in postmenopausal women with AGA. This study was limited to postmenopausal women because of the concern that an inhibitor of type 2 5α-reductase may cause abnormalities of the external genitalia of male fetuses in pregnant women who receive finasteride, based on the findings in males born with type 2 5αreductase deficiency. 12,25 METHODS Patient population Women were eligible for the study if they were 59 years of age or younger at screening, in good physical and mental health, postmenopausal (and amenorrheic for at least 1 year, but no more than 10 years), and had a serum follicle-stimulating hormone (FSH) level of 40 miu/ml or more. They had to have mild to moderate frontal hair thinning assessed as grade 1 or 2 on the Ludwig classification 3 and 3, 4, or 5 on the Savin Female Density Scale. 26,4 Study design This was a 1-year, double-blind, placebo-controlled, randomized study conducted at 8 investigational sites in the United States. All women gave written informed consent before entering the study. After a 2-week placebo run-in, each subject was randomized to receive either oral finasteride 1 mg or placebo once daily for 12 months. Visits were then scheduled for months 1, 3, 6, 9, and 12. Macrophotographs of the identical clipped scalp site in each patient were taken at baseline and at months 3, 6, and 12. Global photographs of the scalp were taken at screening and at months 3, 6, and 12. Investigator assessment and patient hair growth questionnaires were completed at each visit. Scalp biopsy specimens were obtained at baseline and month 12. A suitable biopsy site was selected in an area of hair thinning 10 mm beyond the boundary of the clipped target area used for macrophotographic hair counts. A complete physical examination was performed at screening and at month 12. Vital signs (blood pressure and heart rate) were taken at each visit. Laboratory analyses were done at baseline and at months 1, 6, and 12. Rationale for dose selection. Selection of the 1 mg/day dose of finasteride for the present study was based on the demonstration of the safety and efficacy of this dose in men with AGA and on unpublished data from a previous 2-week study in healthy postmenopausal women, which demonstrated that finasteride doses of 1 mg and 5 mg were equivalent, and better than finasteride 0.2 mg, in reducing serum DHT levels in this population. In addition, the pharmacokinetics of finasteride 1 mg were similar in men and women (data not shown). Efficacy evaluation procedures Four end points were used to evaluate the efficacy of finasteride in these postmenopausal women: hair counts, patient self-assessment, investigator assessment, and global photographic assessment. Hair counts. Hair counts (primary end point) were obtained from computer-assisted scans of macrophotographs of clipped hair in a defined circular target area (1 cm 2 ) in the frontal/parietal (anterior/mid) scalp, centered with a dot tattoo to ensure reproducibility. 23,27 Macrophotographs were converted into dot maps of each visible hair by trained technicians (Canfield Scientific, Inc [CSI], Fairfield, NJ), who were blinded as to patient, treatment, and

770 Price et al J AM ACAD DERMATOL NOVEMBER 2000 Table I. Baseline characteristics of women randomized to study treatment Finasteride 1 mg (n = 67) Placebo (n = 70) Mean age ± SD (y) 53 ± 4 53 ± 5 (range 42-60 y) (range 41-60 y) Mean time since last menses ± SD (y) 8 ± 6 7 ± 5 Mean reported age at onset of hair loss ± SD (y) 43 ± 11 44 ± 9 (range 14-56 y) (range 16-56 y) No. of women with age at onset 40 y 22 18 (range 14-40 y) (range 16-40 y) No. of women with age at onset >40 years 45 52 (range 41-56 y) (range 41-56 y) Mean baseline hair count* ± SD 151 ± 49 164 ± 53 Savin score (No. [%] of women) 3 21 (31.3) 30 (42.9) 4 30 (44.8) 21 (30.0) 5 16 (23.9) 19 (27.1) Ludwig score (No. [%] of women) I (Mild) 22 (32.8) 31 (44.3) II (Moderate) 45 (67.2) 39 (55.7) Concomitant hormone replacement therapy (No. [%] of women) 35 (52.2) 37 (52.9) *Number of hairs measured in a 1-cm 2 circular area at the anterior/mid area of the scalp. time, using a mapping procedure that was validated for precision. 27 Dot maps were converted into hair counts using computer-based scanners and imaging software. 27 Patient self-assessment. Patient self-assessment of hair growth was determined using a modified version of a validated, self-administered hair growth questionnaire, 28 consisting of 4 questions regarding appearance of the hair, growth of hair, slowing down hair loss, and satisfaction with appearance of the hair. Investigator assessment. Investigators assessed patients hair growth using a standardized 7-point rating scale (greatly decreased [-3], moderately decreased [-2], slightly decreased [-1], no change [0], slightly increased [+1], moderately increased [+2], greatly increased [+3]). 22,23 In each patient, assessments were made with comparison to baseline global photographs (see below). Global photographic assessment. Patients were requested to maintain the same hair style, hair color, and hair length throughout the study. Standardized global photographs of the frontal/parietal region were taken with the patient s head in a stereotactic device to ensure consistency of patient positioning and photographic distance. 23 Before being photographed, each patient had her hair parted centrally so that the thinning area was optimally viewed. At the end of the study, an expert panel of 3 dermatologists (E. Olsen, R. Savin, and D. Whiting), blinded as to treatment, independently evaluated hair growth or loss by comparing baseline photographs with follow-up photographs of each patient, using the same standardized 7-point rating scale as in the investigator assessment (see above). Macro and global photographs (Kodak KR-64 35-mm slide film) were taken using a Nikon N-6006 camera with a Nikon 60 mm f2.8 lens and a CSI Twin Flash. 27 Film emulsion, lighting, framing, exposure, and reproduction ratios were held constant. Photographs were processed at Qualex Laboratories, Fairlawn, NJ, and returned to CSI for technical evaluation and quality assurance. Scalp biopsies. Ninety-four of the 137 women enrolled in this study consented to having scalp biopsies. Serial 4-mm punch biopsies of scalp were taken in the frontal/parietal region of the scalp, adjacent to the circular clipped area that had been designated for hair counts by macrophotography. Biopsies were cut horizontally, about 1 to 1.5 mm beneath the dermoepidermal junction and paraffinembedded. Horizontal sections were then made through the entirety of the embedded tissue. At the end of the study, all slides were read by one dermatologist (D. Whiting) who was blinded as to patient, treatment, and time. All terminal hair bulbs, terminal anagen, catagen and telogen hairs, and vellus and velluslike (miniaturized) hairs, were counted. 29-31 Catagen hairs were included in the telogen count. Laboratory assessments Laboratory parameters included hematology, urinalysis, serum chemistry, hormone analysis, and bone marker analyses. Serum chemistry, hematology, and bone marker analyses were performed at Mayo Medical

J AM ACAD DERMATOL VOLUME 43, NUMBER 5 Price et al 771 Fig 1. Mean hair count change from baseline (± 1 SE) over 12 months in the frontal/parietal (anterior/mid) scalp. Group numbers: finasteride 1 mg, n = 66; placebo, n = 69. Table II. Disposition of patients Finasteride 1 mg (n = 67) Placebo (n = 70) No. (%) No. (%) No. of patients completing 12 mo of treatment 62 (92.5) 63 (90.0) No. of patients who did not complete study 5 (7.5) 7 (10.0) Reasons for not completing study: Clinical adverse event 2 (3.0) 1 (1.4) Lost to follow-up 1 (1.5) 3 (4.3) Withdrew consent 0 3 (4.3) Noncompliance 1 (1.5) 0 Lack of efficacy 1 (1.5) 0 Table III. Women with self-assessed improvement in scalp hair at month 12 Finasteride 1 mg (n = 67) Placebo (n = 70) Patient self-administered hair growth questionnaire No. (%) No. (%) Q1: Appearance of hair 32 (48) 29 (42) Q2: Growth of hair 30 (44) 32 (53) Q3: Slowing hair loss 33 (50) 33 (49) Q4: Satisfaction with hair overall 12 (18) 16 (23) Laboratories (Rochester, Minn). Serum hormone assays were performed at Endocrine Sciences, Inc (Calabasas Hills, Calif). DHT, testosterone, androstenedione, estradiol, and androstanediol glucuronide were measured by radioimmunoassay. Serum-free testosterone was measured using equilibrium dialysis against a buffer containing radiolabeled testosterone. Dehydroepiandrosterone sulfate (DHEAS) was measured as DHEA by radio-immunoassay after enzymolysis of the DHEAS. Prolactin was measured by a chemiluminescent sandwich method. Luteinizing hormone and follicle-stimulating hormone were measured using an immunochemiluminometric assay. Thyroid-stimulating hormone was measured using a two-site immunometric procedure and chemiluminescent detection. Urinary levels of N-telopeptide were determined by an enzyme-linked immunosorbent assay using a kit from Ostex International, Inc (Seattle, Wash). N-telopeptide was determined after adjustment for urinary creatinine levels. Urinary creatinine was assayed by the Jaffe alkaline picrate reaction (Medical Research Laboratories, Highland Heights, Ky). Serum bone-specific alkaline phosphatase was measured by means of an enzyme-linked immunoradiometric assay using a kit from Hybritech Inc (San Diego, Calif). Statistical analysis The primary efficacy end point for this study was change from baseline in hair count, assessed in all subjects (intent-to-treat population, ie, all women

772 Price et al J AM ACAD DERMATOL NOVEMBER 2000 Fig 2. Investigator assessment of hair growth at month 12 (percentage of women with change in hair growth). Fig 3. Global photographic assessment at month 12 (percentage of women with change in hair growth). Table IV. Scalp follicular counts at baseline and month 12 Finasteride 1 mg (n = 44) Placebo (n = 50) Ratio of Ratio of month 12 month 12 Ratio (± SE) Baseline Month 12 to baseline Baseline Month 12 to baseline Anagen/telogen 6.1 ± 0.7 7.9 ± 1.1 1.3 ± 0.2 5.7 ± 0.7 7.4 ± 0.9 1.3 ± 0.2 Terminal/miniaturized hair 1.7 ± 0.2 2.1 ± 0.2 1.2 ± 0.1 1.9 ± 0.2 2.3 ± 0.3 1.2 ± 0.1 with a baseline and at least one postrandomization efficacy measurement). Analysis of variance (ANOVA) was used to compare the change from baseline in the month 12 hair counts between the two treatment groups (ie, finasteride versus placebo groups). The secondary efficacy end points of the investigator and global photographic assessments represent categorical data. Therefore a unit interval scale was assumed for these variables to enable analysis using ANOVA. For the other secondary end point, the patient self-administered hair growth questionnaire, a global analysis was performed incorporating the scores across all 4 questions at the month 12 time point. For the biopsy end points (ratios of anagen to telogen and terminal to miniaturized hairs), a twoway ANOVA model utilizing least squares was used to compare the month 12 change from baseline between the finasteride and placebo groups, the results of which were corroborated by the Wilcoxon ranked sum test.

J AM ACAD DERMATOL VOLUME 43, NUMBER 5 Price et al 773 ANOVA was performed for the biochemical parameters. The Cochran-Mantel-Haenszel test on ranks was used to compare treatment effects between groups. The analyses of the biochemical parameters, except for bone markers, were performed only on patients who were not receiving hormone replacement therapy. Bone markers were analyzed separately for patients receiving hormone replacement therapy and for those not receiving hormone replacement therapy. Patients were excluded from the bone marker analysis if their hormone replacement therapy status changed during the study. Comparison of the proportion of patients with an adverse event (ie, drug-related and unrelated adverse events) was done between the finasteride and placebo groups using Fisher s exact test. RESULTS Baseline characteristics One hundred thirty-seven women with mild to moderate hair thinning in the frontal/mid scalp region were enrolled in the study. The two treatment groups were similar in terms of all baseline characteristics (Table I). Approximately half (35 patients, or 52%, in the finasteride group, and 37 patients, or 53%, in the placebo group) of the patients in each treatment group were receiving concomitant hormone replacement therapy during the study. Sixtytwo finasteride-treated patients (92.5%) and 63 placebo-treated patients (90%) completed the study (Table II). Five patients (7.5%) in the finasteride group and 7 patients (10%) in the placebo group did not complete the study (Table II). Two finasteridetreated patients withdrew because of an adverse event (one with nausea and the other with colon cancer; in both cases the adverse event was assessed by the investigator as being unrelated to treatment). One patient in the placebo group withdrew because of an adverse event (hair shedding, assessed by the investigator as drug-related). Hair count During the 1-year study, both treatment groups demonstrated a similar degree of hair loss by hair count (Fig 1). At month 12, the mean decrease from baseline in hair count was 8.7 hairs (95% confidence interval [CI] 15.2, 2.3; P <.01) in the finasteride group and 6.6 hairs (95% CI 13.0, 0.1; P <.05) in the placebo-treated group, with no significant difference between the treatment groups. Patient self-assessment There was no significant difference between the finasteride and placebo groups in the percentage of patients reporting improvement in scalp hair from baseline at month 12 for any of the questions on the patient self-administered hair growth questionnaire (Table III). Moreover, there were no significant differences between the treatment groups in the global analysis or in the mean scores for the patient selfadministered hair growth questionnaire. Investigator assessment There was no significant difference between the finasteride and placebo groups in the investigator assessment of change in hair growth (Fig 2). The majority of patients in both treatment groups (67% in the finasteride group and 54% in the placebo group) were assessed as having a slight to moderate improvement from baseline by the investigator assessment score at month 12. Global photographic assessment Assessment of global photographs showed no significant difference between the finasteride and placebo groups during the course of the study (Fig 3). At month 12, the expert panel rated 11% of finasteride-treated subjects as having slightly increased hair growth from baseline compared with 16% of placebo-treated subjects. Subgroup analyses The efficacy results were the same for all analyses, regardless of whether or not the data were stratified by hormone replacement therapy, age, or Ludwig classification of hair loss. There were no significant differences between the finasteride and placebo groups for any of the parameters assessed. Scalp biopsy Assessment of scalp biopsy results also showed no significant difference between the finasteride and placebo groups during the course of the study. There were no differences between the two treatment groups in the change from baseline in anagen/telogen ratio or in the change from baseline in the ratio of terminal to miniaturized hairs, at month 12 (Table IV). Serum hormones and bone markers Although the baseline level of serum DHT in the postmenopausal women was low, being similar to that reported in castrated men, 32 treatment with finasteride led to relatively large reductions in serum DHT and androstanediol glucuronide and a small reduction in DHEAS compared with placebo (Table V). Finasteride had no significant effect on total serum testosterone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, androstenedione, estradiol, or prolactin. Analysis of bone markers (bone-specific alkaline phosphatase and N-

774 Price et al J AM ACAD DERMATOL NOVEMBER 2000 Table V. Serum hormone levels at baseline and month 12* Finasteride 1 mg Normal range Median serum level ± SD Median % for serum level change from Hormone in women No. Baseline Month 12 baseline Dihydrotestosterone (ng/dl) <2-12 19 5.2 ± 3.2 2.9 ± 2.4 42.4% Total testosterone (ng/dl) 6-49 25 18.0 ± 28.8 14.0 ± 31.1 5.9% DHEAS (µg/dl) 6-140 26 59.0 ± 31.5 52.5 ± 33.5 21.2% Androstanediol glucuronide (ng/dl) 10-160 19 64.0 ± 97.9 18.0 ± 38.6 70.0% *Excluding women on hormone replacement therapy. Based on nonparametric rank analysis. Table VI. Summary of selected adverse events* Finasteride 1 mg Placebo (n = 67) (n = 70) Total No. of patients with 53 55 one or more clinical adverse events Headache 5 11 Depression 1 3 Nausea 2 2 Hot flashes 0 2 *Adverse events were selected that were judged to be of particular clinical interest in a postmenopausal female patient population. telopeptide) indicated that there were no significant differences between the finasteride and placebo groups, regardless of whether or not patients were receiving hormone replacement therapy. Safety The overall incidence and nature of all (ie, drugrelated and unrelated) clinical adverse events reported during the 12-month treatment period were similar for both treatment groups; 53 patients (79.1%) reported clinical adverse events in the finasteride group compared with 55 patients (78.6%) in the placebo group. There were no significant differences between the finasteride and placebo groups in drugrelated clinical or laboratory adverse events. Only one patient in the finasteride group reported a drugrelated adverse event (folliculitis), which resolved while the patient remained on finasteride. Five patients in the placebo group reported drug-related adverse events (2 cases of increased body hair growth, 1 case of sweating and hot flashes, and 1 case each of hot flashes and headache). No drugrelated laboratory adverse events were reported in the finasteride or placebo groups. The nature and incidence of adverse events of particular interest in this population of postmenopausal women, including headache, nausea, hot flashes, and depression, were similar in both the finasteride and placebo groups (Table VI). DISCUSSION This 12-month study demonstrated that finasteride 1 mg did not improve scalp hair growth in postmenopausal women with AGA. Analysis of hair count data after 1 year of therapy revealed that patients in both the finasteride and placebo groups had modest, but statistically significant, decreases in hair counts from baseline. These decreases in hair count for the two treatment groups were not significantly different. Analysis of the other efficacy end points also failed to demonstrate any effect of finasteride on hair growth in these patients. The patient self-administered hair growth questionnaire showed no difference between women taking finasteride or placebo at month 12 for any of the individual questions. Similarly, there was no difference between the finasteride and placebo groups in the investigator assessment of change in hair growth. Assessment of global photographs by the expert panel showed no significant difference between the finasteride and placebo groups during the course of the study. Evaluation of scalp biopsy specimens also revealed no differences between the two treatment groups in the change from baseline in anagen/telogen ratio or in the ratio of terminal to miniaturized hairs at month 12. We can speculate as to why finasteride did not show any efficacy in improving hair growth in these postmenopausal women. The baseline level of serum DHT in these women was low, being similar to that reported in castrated men. 32 Nonetheless, finasteride still produced relatively large reductions in serum DHT and androstanediol glucuronide and a

J AM ACAD DERMATOL VOLUME 43, NUMBER 5 Price et al 775 Placebo P value Median serum level ± SD Median % (between-group change from comparison for % No. Baseline Month 12 baseline change from baseline) 24 5.0 ± 3.4 3.5 ± 3.1 17.3%.002 26 18.0 ± 11.6 14.5 ± 11.9 17.6%.786 26 60.5 ± 39.4 50.0 ± 39.7 4.7%.038 22 88.0 ± 103.1 105.0 ± 84.9 0.4% <.001 small reduction in DHEAS in these women, indicating that 5α-reductase had been inhibited. AGA usually manifests itself in the second, third, and fourth decades in both genders, and in this age group, levels of 5α-reductase have been measured in frontal and occipital scalp hair follicles. 5,24 Women and men with AGA have increased levels of 5α-reductase in frontal follicles compared with occipital follicles, although women have only about one third the amount that men have. 24 Levels of 5α-reductase in the scalps of older women with AGA have not been systematically measured. However, in men with AGA, it has been reported that increased DHT formation in the scalp is most pronounced in young men and that scalp DHT formation decreases with age. 33-35 The clinical relevance of these findings is not known and awaits studies on the effects of 5α-reductase inhibition in older men with AGA. Other factors in scalp hair follicles besides 5α-reductase may also be important in the pathophysiology of AGA. These likely include the level of aromatase, the enzyme that converts testosterone to estradiol, and the number of androgen receptors. 24 The role of these factors in hair thinning in postmenopausal women is not known. There may be another explanation why finasteride did not improve hair growth in the postmenopausal women in this study. Women and men in the later decades of life may develop thinning scalp hair, which may not be 5α-reductase or DHTdependent. This late-onset decrease in scalp hair density, or senescent hair thinning, has not been thoroughly studied, but one might speculate that it may be similar to the familiar decrease in lower limb, axillary, and pubic hair that occurs with advancing age. Senescent scalp hair thinning may appear as a continuum with earlier-onset AGA or may appear for the first time in someone who had dense hair until the later decades. It is possible that some of the women in this study had late-onset or senescent thinning that will not respond to finasteride, a highly specific inhibitor of type 2 5α-reductase. Finasteride was generally well tolerated by the women in this study. No clinically significant differences were seen in the numbers or types of adverse events reported in the finasteride and placebo groups. In conclusion, in postmenopausal women with AGA ranging in age from 41 to 60 years, finasteride was not effective in improving hair loss. REFERENCES 1. Olsen EA. Androgenetic alopecia. In: Olsen EA, editor. Disorders of hair growth: diagnosis and treatment. New York: McGraw- Hill; 1994. p. 257-83. 2. Frieden IJ, Price VH. Androgenetic alopecia. In: Thiers BH, Dobson RL, editors. Pathogenesis of skin disease. New York: Churchill Livingstone; 1986. p. 41-55. 3. Ludwig E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br J Dermatol 1977;97:247-54. 4. Olsen EA. The midline part: an important physical clue to the clinical diagnosis of androgenetic alopecia in women. J Am Acad Dermatol 1999;40:106-9. 5. Kaufman KD. Androgen metabolism as it affects hair growth in androgenetic alopecia. Dermatol Clin 1996;14:697-711. 6. Russell DW, Wilson JD. Steroid 5α-reductase: two genes/two enzymes. Annu Rev Biochem 1994;63:25-61. 7. Harris G, Azzolina B, Baginsky W, et al. Identification and selective inhibition of an isozyme of steroid 5α-reductase in human scalp. Proc Natl Acad Sci U S A 1992;89:10787-91. 8. Thigpen AE, Silver RI, Guileyardo JM, et al. Tissue distribution and ontogeny of steroid 5α-reductase isozyme expression. J Clin Invest 1993;92:903-10. 9. Eicheler W, Dreher M, Hoffmann R, et al. Immunohistochemical evidence for differential distribution of 5α-reductase isoenzymes in human skin. Br J Dermatol 1995;133:371-6. 10. Bayne EK, Flanagan J, Einstein M, et al. Immunohistochemical localization of types 1 and 2 5α-reductase in human scalp. Br J Dermatol 1999;141:481-91. 11. Thiboutot D, Knaggs H, Gilliland K, et al. Activity of type 1 5αreductase in the follicular infrainfundibulum compared with the epidermis. Br J Dermatol 1997;136:166-71. 12. Imperato-McGinley J, Guerrero L, Gautier T, et al. Steroid 5α-

776 Price et al J AM ACAD DERMATOL NOVEMBER 2000 reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974;186:1213-5. 13. Walsh PC, Madden JD, Harrod MJ, et al. Familial incomplete male pseudohermaphroditism, Type 2: decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med 1974;291:944-9. 14. Imperato-McGinley J. 5α-reductase-2 deficiency. Curr Ther Endocrinol Metab 1997;6:384-7. 15. Andersson S, Berman DM, Jenkins EP, et al. Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism. Nature 1991;354:159-61. 16. Drake L, Hordinsky M, Fiedler V, et al. The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. J Am Acad Dermatol 1999;41:550-4. 17. Dallob AL, Sadick NS, Unger W, et al. The effect of finasteride, a 5α-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. J Clin Endocrinol Metab 1994;79:703-6. 18. Liang T, Rasmusson GH, Brooks JR. Biochemical and biological studies with 4-aza-steroidal 5α-reductase inhibitors. J Steroidal Biochem 1983;19:385-90. 19. Liang T, Heiss CE, Cheung AH, et al. 4-Azasteroidal 5α-reductase inhibitors without affinity for the androgen receptor. J Biol Chem 1984;259:734-9. 20. Rittmaster RS. Finasteride. N Engl J Med 1994;330:120-5. 21. Rasmusson GH, Liang T, Brooks JR. A new class of 5α-reductase inhibitors. In: Roy AK, Clark JH, editors. Gene regulation by steroid hormones II. New York: Springer-Verlag; 1983. p. 311-34. 22. Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol 1998;39:578-88. 23. Leyden J, Dunlap F, Miller B, et al. Finasteride in the treatment of men with frontal male pattern hair loss. J Am Acad Dermatol 1999;40:930-7. 24. Sawaya ME, Price VH. Different levels of 5α-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. J Invest Dermatol 1997; 109:296-300. 25. US package insert for Propecia (finasteride 1mg tablets). Physicians desk reference. 52nd ed. Montvale (NJ): Medical Economics Company; 1998. p. A53-5. 26. Savin RC. Evaluating androgenetic alopecia in male and female patients: an improved visual method of classifying and tracking hair loss using computer-generated male and female pattern and density scales. Kalamazoo: The Upjohn Company; January 1994. 27. Canfield D. Photographic documentation of hair growth in androgenetic alopecia. Dermatol Clin 1996;14:713-21. 28. Barber BL, Kaufman KD, Kozloff RC, et al. A hair growth questionnaire for use in the evaluation of therapeutic effects in men. J Dermatol Treat 1998;9:181-6. 29. Headington JT. Transverse microscopic anatomy of the human scalp. Arch Dermatol 1984;120:449-56. 30. Whiting DA. Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia. J Am Acad Dermatol 1993;28:755-63. 31. Whiting DA.The value of horizontal sections of scalp biopsies. J Cutan Aging Cosmet Dermatol 1990;1:165-73. 32. Zverina J, Hampl R, Sulocava J, Starka L. Hormonal status and sexual behaviour of 16 men after surgical castration. Arch Ital Urol Nefrol Androl 1990;62:55-8. 33. Schweikert HU, Wilson JD. Regulation of human hair growth by steroid hormones: I. Testosterone metabolism in isolated hairs. J Clin Endocrinol Metab 1974;38:19-22. 34. Takashima I, Montagna W. Studies of common baldness of the stump-tailed macaque: VI. The effect of testosterone on common baldness. Arch Dermatol 1971;103:527-34. 35. Price VH. Testosterone metabolism in the skin: a review of its function in androgenetic alopecia, acne vulgaris, and idiopathic hirsutism, including recent studies with antiandrogens. Arch Dermatol 1975;111:1496-502. BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the Journal of the American Academy of Dermatology are available to subscribers (only) for the 2000 issues from the Publisher at a cost of $123.00 for domestic, $151.94 for Canadian, and $142.00 for international for volume 42 (January-June) and volume 43 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Subscription Customer Service, 6277 Sea Harbor Dr, Orlando, FL 32887; phone 800-654-2452 or 407-345-4000. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular journal subscription.