Validation of scalp coverage scoring methods for scalp hair loss in male pattern hair loss (androgenetic alopecia)

BACKGROUND: Global evaluation of hair loss in male subjects affected by androgenetic alopecia has been proposed as a means for monitoring changes over time, including placebo-controlled drug efficacy studies. Because of the potential impact of subjectivity (e.g. placebo effect) of clinical investigators, global photographs (GPs) have been introduced as a more objective record. Examination of paired before and after pictures and rating on a seven-point scale (from greatly decreased -3 to greatly increased +3) have been historically introduced by United States of America (US) experts. METHODS: Based on published GPs and original GPs obtained at our clinical research facility, we developed a training set in order to allow European Union (EU) observers to practice and compare with ratings by the US experts. RESULTS: After training with the seven-point scale, there was a positive correlation between three US and three EU ratings (n=52 paired images from 35 different subjects, r=0.795). The results of a test-retest evaluation was performed on 18 paired images from the initial image collection by the three EU experts. Correlation r=0.806 and identical scores in 78% of cases documents a reproducibility similar to the single one US expert published data (119 subjects, retest correlation 0.76 with 75% identical duplicate ratings). Seventeen subjects taken from a placebo-controlled trial had GPs at 6 and 12 months. The average difference between an efficacious drug treatment and the placebo were almost similar in the US (0.833) as in the EU (0.689) expert panels. We also trained the EU experts in performing the scalp coverage scoring (SCS), a novel system for the global evaluation of scalp hair in vivo and on GP. SCS was performed on single images (randomised as to time and treatment) taken from the same set of 17 paired GPs. This showed a between-group difference of 0.055 at 6 months and 0.201 at 12 months, i.e. 5% improved coverage in favour of the active group. CONCLUSION: After completion of our study, US and trained - calibrated EU experts seem equally valuable in comparing before-after GPs. SCS can also be used on GPs and may support the clinical investigator during inclusion of test subjects and for real-time efficacy evaluation during the trial.     

Treatment of female pattern hair loss with oral antiandrogens

BACKGROUND: It has not been conclusively established that female pattern hair loss (FPHL) is either due to androgens or responsive to oral antiandrogen therapy. OBJECTIVES: To evaluate the efficacy of oral antiandrogen therapy in the management of women with FPHL using standardized photographic techniques (Canfield Scientific), and to identify clinical and histological parameters predictive of clinical response. METHODS: For this single-centre, before-after, open intervention study, 80 women aged between 12 and 79 years, with FPHL and biopsy-confirmed hair follicle miniaturization [terminal/vellus (T/V) hair ratio < or = 4 : 1] were photographed at baseline and again after receiving a minimum of 12 months of oral antiandrogen therapy. Forty women received spironolactone 200 mg daily and 40 women received cyproterone acetate, either 50 mg daily or 100 mg for 10 days per month if premenopausal. Women using topical minoxidil were excluded. Standardized photographs of the midfrontal and vertex scalp were taken with the head positioned in a stereotactic device. Images were evaluated by a panel of three clinicians experienced in the assessment of FPHL, blinded to patient details and treatment and using a three-point scale. RESULTS: As there was no significant difference in the results or the trend between spironolactone and cyproterone acetate the results were combined. Thirty-five (44%) women had hair regrowth, 35 (44%) had no clear change in hair density before and after treatment, and 10 (12%) experienced continuing hair loss during the treatment period. Ordinal logistic regression analysis to identify predictors of response revealed no influence of patient age, menopause status, serum ferritin, serum hormone levels, clinical stage (Ludwig) or histological parameters such as T/V ratio or fibrosis. The only significant predictor was midscalp clinical grade, with higher-scale values associated with a greater response (P = 0.013). CONCLUSION: Eighty-eight percent of women receiving oral antiandrogens could expect to see no progression of their FPHL or improvement. High midscalp clinical grade was the only predictor of response identified. A placebo-controlled study is required to compare this outcome to the natural history of FPHL.     

Significant relationship between temporal hair loss and other scalp areas in female pattern hair loss

Female pattern hair loss affects the central scalp, sparing the frontal hairline. The temporal area can also be affected by hair loss. We investigated the degree of temporal hair loss and correlation of other sites of scalp hair loss in Korean female pattern hair loss patients. A total of 109 women with female pattern hair loss were enrolled in this retrospective analysis. We measured hair density and thickness in five scalp sites including the frontal, vertex, occipital and bilateral temporal areas by phototrichogram. Frontal and vertex area hair loss were classified according to the Basic and Specific (BASP) classification, and temporal scalp and occiput areas were also assessed. Eighty-nine patients showed temporal hair loss. The mean of the hair density was lowest in the temporal area among all scalp areas. Total and thick hair densities of the frontal scalp were correlated with those of the vertex, temporal scalp and occiput in descending order, and hair thickness of the frontal scalp was more related with that of the temporal scalp than the vertex. In this study, temporal involvement is evident in female pattern hair loss. We suggest that temporal involvement should be added to pattern hair loss classification, especially BASP classification.     

Role of genetics and sex steroid hormones in male androgenetic alopecia and female pattern hair loss: an update of what we now know

The role of genetic predisposition and the influence of sex steroid hormones are indisputable to the pathogenesis of male androgenetic alopecia (MAGA). The role of sex steroid hormones in female pattern hair loss (FPHL) is less known. A good knowledge of the pathophysiology underlying MAGA and FPHL empowers the clinician to confidently counsel patients and make informed therapeutic decisions. Vigorous research in recent years has provided greater insight into the role of genetics and sex steroids in physiological hair growth and cycling, as well as in hair follicle miniaturization, the histological hallmark of MAGA and FPHL. In the present review article directed towards clinicians, we discuss the current understanding of the role of androgens and oestrogens, as well as genetic associations with MAGA and FPHL. We also briefly discuss the interpretation of direct-to-consumer genetic testing for baldness to help clinicians understand the limitations of such tests.     

Hair density, hair diameter and the prevalence of female pattern hair loss

BACKGROUND: Female pattern hair loss is common but estimates of its prevalence have varied widely. The relationships between the clinical diagnosis of female pattern hair loss and objective measurements of hair density and hair diameter have not previously been evaluated. OBJECTIVES: To determine the prevalence of female pattern hair loss and to relate the clinical findings to hair density and hair diameter. METHODS: We examined 377 women, aged 18--99 years, who presented to a general dermatology clinic with complaints unrelated to hair growth (the unselected sample). A second group of 47 women referred with typical female pattern hair loss was included in analyses of the relationships between hair density, hair diameter and the clinical diagnosis. Hair density was measured using a photographic method. In each subject the major and minor axis diameters were measured in a random sample of 50 hairs. RESULTS: Six per cent of women aged under 50 years were diagnosed as having female pattern hair loss, increasing to 38% in subjects aged 70 years and over. The mean +/- SEM hair density was 293 +/- 61.3 hairs cm(-2) at age 35 years, falling to 211 +/- 55.1 hairs cm(-2) at age 70 years. Hair density showed a normal distribution in the unselected sample. Most women classified as having female pattern hair loss had hair densities within the lower half of the normal distribution. The perception of hair loss was determined mainly by low hair density (ANOVA P < 0.001), but there was overlap in hair density between women classified as having Ludwig I hair loss and the no hair loss group, which was partly accounted for by differences in mean hair diameter (ANOVA P < 0.001). Low hair density was associated with fewer hairs of all diameters. CONCLUSIONS: Hair density in women is distributed as a normal variable, indicating that it is determined as a multifactorial trait. Women with female pattern hair loss have a hair density which falls below the mean but lies within the spectrum of the normal distribution, although other factors, including hair diameter, may affect the subjective impression of hair loss. The hair diameter data suggest that low hair density is not due to progressive diminution in hair follicle size and that follicular miniaturization may occur within the space of a single hair cycle.     

Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day in women with female pattern hair loss

Female pattern hair loss (FPHL) presents with diffuse thinning over the mid‐frontal scalp, for which various treatment modalities have been tried. Although currently, oral 5 α‐reductase inhibitors such as finasteride are being used, their clinical efficacy remains controversial. We retrospectively investigated 544 premenopausal or postmenopausal patients with FPHL who were prescribed finasteride at a dose of 2.5 mg/day. Our study excluded patients with a follow‐up period of < 3 months and patients who were prescribed other FPHL treatment modalities including topical minoxidil. Finally, 112 patients were evaluated based on their medical records and clinical photographs. Based on assessment using the Ludwig scale at the time of their initial visit, among 112 patients studied, 59 patients were classified as belonging to grade I, 47 were grade II, and 6 were grade III. Using global photographs, we found that 33 (29.5%) of the 112 patients studied showed slight improvement, 73 (65.2%) showed significant improvement, whereas no change was recorded in 6 (5.4%). We could demonstrate efficacy of administration of finasteride at a dose of 2.5 mg/day for patients with FPHL and also found that finasteride has a better effect on hair growth when patients had a lower Ludwig score and an older age at onset     

Distinctive age distribution and hair loss pattern putatively highlighting uniqueness of Japanese cases of fibrosing alopecia in a pattern distribution

Fibrosing alopecia in a pattern distribution (FAPD) is a unique entity which presents clinicopathological characteristics of both male/female pattern androgenetic alopecia (AGA) and lichen planopilaris (LPP). This entity was first reported in 2000 and its criteria was recently proposed. Etiopathogenesis of FAPD has been speculated to be immunological destruction involving miniaturized hair follicles but still remains elusive. To date, few Asian FAPD cases have been reported in the literature. In this study, Japanese FAPD cases were identified based on the aforementioned criteria and analyzed to delineate clinicopathological characteristics. By retrospectively revisiting medical records and clinical photographs, 24 Japanese cases comprising 17 women and seven men were diagnosed as FAPD. All male patients had disease onset by their early 30s, whereas most female patients had developed the condition in middle age or later. Their initial diagnoses prior to the diagnostic confirmation of FAPD were mostly LPP. Based on the clinical phenotypes, the cases were categorized into AGA and LPP types. These subtypes were characterized by foremost trichoscopic and histopathological findings of AGA or LPP, respectively. Unlike previously reported cases, our patients tended to manifest hair loss in both vertex and frontal to mid-scalp with minimal regression of anterior hairline, manifesting unique “parachute” pattern, which has been reported as a representative characteristic of East Asian AGA in the literature. Anti-inflammatory therapies seemed to be effective to deter hair loss but insufficient to achieve improvement. Further accumulation of the cases is necessary; however, these findings may provide additional pathophysiological insights into FAPD and highlight uniqueness of the etiology and clinical phenotype of Japanese FAPD putatively influenced by racial predispositions.     

Occipital involvement in female pattern hair loss: histopathological evidences

Background Female pattern hair loss (FPHL) is characterized by diffuse thinning of hair in the frontal and parietal areas of the scalp, and preservation of the frontal hairline is the norm. Hair on the occipital scalp is thought to be preserved. Objective To investigate whether the occipital area is involved in FPHL or whether there is a diffuse type of FPHL. Methods Forty female patients who had complained about hair loss for more than a year and were diagnosed with FPHL according to the Ludwig classification were included. Two punch biopsies from both the midscalp and the occiput were taken. Histological sections were prepared horizontally and stained with haematoxylin and eosin. Terminal follicles, vellus like follicles, anagen, telogen, catagen follicles, hair bulbs and telogen germinal units were counted in two sections of the upper dermis and the dermal‐subcutaneous junction. If the terminal/vellus ratio was lower than 4:1, the diagnosis of androgenetic alopecia (AGA) was made. When the ratio was between four and seven to one, AGA was suspected. Results While 29 of 40 patients (72.5%) had findings consistent with AGA on the midscalp, 11 of 40 (27.5%) displayed signs of suspected AGA. Ten of 40 patients (25%) had AGA involving the occiput. Conclusion The involvement of the occipital scalp is significant in FPHL. In some patients, this situation may be so apparent that clinically visible alopecia is seen. However, in other patients, it may also present only as thinning.     

Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss

Background  Female pattern hair loss (FPHL) is a common trait in which androgens and oestrogens may have a pathogenic role. The aromatase enzyme converts androgens to oestrogens in scalp hair follicles and is differentially expressed in balding and nonbalding scalps of women. Sequence variation in the gene encoding aromatase, CYP19A1 , might influence the risk of developing FPHL.
Objectives  To examine the role of CYP19A1 genetic variation in the heritability of FPHL.
Methods  We investigated associations between FPHL and 61 tag single nucleotide polymorphisms (SNPs) representing variation in and around CYP19A1 in 484 caucasian women with grades 3–5 FPHL on the Sinclair scale, and 471 caucasian women with no evidence of hair loss.
Results  For the tag SNP rs4646 (overall genotype frequencies: CC, 53·6%; AC, 39·3%; AA, 7·1%), the genotype CC was more frequent in women with FPHL (58·1%) than controls (48·9%) ( P  =   0·006). Although this result did not achieve experiment-wide significance ( P  <   0·001 by permutation testing), subanalyses according to sources of recruitment and ages at presentation revealed consistent patterns of association. In particular, young cases (< 40 years) had the highest frequency of the CC genotype (68·2%) among all subgroups.
Conclusions  These findings suggest that the common rs4646 C allele, which has been associated previously with higher circulating oestrogen levels, might be associated with predisposition to FPHL.     

Psychological aspects of hair disease

Balding men are viewed as less desirable in a physical, personal, and social sense. Given the stereotype, it is not surprising that some men with androgenetic alopecia (AGA) appear to have a lower self-image, depression resulting in increased introversion, and increased feelings of unattractiveness. Ours is a culture that places a premium on physical appearance. In this context, appearance-altering conditions can be psychosocially insidious, especially conditions such as AGA with an uncertain course and a negative social meaning. To date, little or no data have been available regarding the psychosocial and quality-of-life aspects of AGA in a representative sample of community men. It is unknown whether AGA is a causal factor in the development of low self-esteem, depression, introversion, and feeling of unattractiveness, or whether there are underlying problems in certain patients prior to hair loss. Longitudinal studies will be important to investigate the temporal relationships between the degree of hair loss and psychosocial variables associated with AGA. A patient with male pattern baldness will be better treated and consequently more satisfied (better quality of life) if he receives effective anti-alopecia agents and simultaneously is evaluated and treated, if needed, for his psychological disorder.     

Polymorphic CAG repeat numbers in the androgen receptor gene of female pattern hair loss patients

Female pattern hair loss (FPHL) is frequently referred to as female androgenetic alopecia (FAGA). However, the role of androgen in this type of hair loss remains uncertain. We previously reported greater therapeutic efficacy of finasteride in Japanese male androgenetic alopecia (MAGA) patients in cases where the CAG repeats of the androgen receptor (AR) gene were short. To examine the correlation between CAG repeat numbers and the therapeutic efficacy of finasteride in FPHL patients, the efficacy of finasteride (1 mg/day) was evaluated macroscopically. Because women have two X-chromosomes, the shorter and longer CAG repeat numbers were analyzed in 37 Japanese FPHL patients, then the correlation of these factors was statistically analyzed by anova. No statistical significance in terms of the differences in CAG repeat numbers was detected among the four groups classified on the basis of the efficacy of finasteride. From these results, it may be concluded that the efficacy of this medicine in each FPHL patient cannot be predicted by the CAG repeat numbers in the AR gene.     

瘢痕性女性型脱发1例

报道1例瘢痕性女性型脱发。患者女,36岁,因脱发加重十余年就诊。皮肤科检查：弥漫性头发稀疏,发质细软,可见多数铅笔橡皮擦样大小的灶性秃发区。TrichoScan检查提示额部毛发密度明显降低,毛发直径变异度大于20%,毳毛比例明显增加。毛发镜检查：毳毛增加,可见大量直径3 ~ 5 mm的灶性秃发区域,部分毛囊开口消失,可...     

Women who present with female pattern hair loss tend to underestimate the severity of their hair loss

BACKGROUND: Female pattern hair loss (FPHL) is the preferred term for androgenetic alopecia in women. FPHL can be a source of considerable distress for affected women. Our hypothesis was that women with FPHL who seek treatment would rate their condition as more severe than would their treating doctors. OBJECTIVES: To identify discrepancies between the severity ratings of the women and their clinicians. METHODS: Participants were 30 women receiving treatment for biopsy-proven FPHL and 44 women on a waiting list to receive treatment for FPHL. Each woman completed a self-report photographic measure of severity of hair loss, specifically developed for the current study. RESULTS: Although no difference was found between the severity ratings of women receiving treatment and their clinicians, it was found that women in the waiting list group underestimated the severity of their hair loss compared with their clinicians' ratings. CONCLUSION: The results indicate that FPHL-affected women who seek treatment for FPHL do not overestimate the severity of the hair loss; in fact, they tend to underestimate. The present findings have implications for the treatment of FPHL.     

Treatment of female pattern hair loss with a combination of spironolactone and minoxidil

A 53-year-old woman with clinical evidence of female pattern hair loss and histological evidence of androgenetic alopecia was initially treated with the oral antiandrogen spironolactone 200 mg daily. Serial scalp photography documented hair regrowth at 12 months; however, the hair regrowth plateaued, and at 24 months there had been no further improvement in hair density. Twice daily therapy with topical minoxidil 5% solution was then introduced and further regrowth documented, confirming the additive effect of combination therapy.