Progression of hair loss in men with androgenetic alopecia (male pattern hair loss): long-term (5-year) controlled observational data in placebo-treated patients

Relatively little is known about the progression of androgenetic alopecia (AGA; male pattern hair loss) in untreated men. We evaluated the long-term (5-year) progression of AGA in men treated with placebo in a controlled clinical trial setting. We analyzed pooled data over 5 years from two replicate studies with finasteride 1 mg/day in men with predominantly vertex-pattern AGA. Each study consisted of an initial 1-year, randomized, double-blind, placebo-controlled base study and four consecutive, 1-year, double-blind, placebo-controlled extension studies. Change over time in scalp hair growth was evaluated by four predefined endpoints: scalp hair counts; assessment of standardized clinical photographs by an expert panel; investigator clinical assessment; and patient self-assessment. All four predefined endpoints demonstrated progressive scalp hair loss in men receiving placebo over the 5-year study period, with a loss of 239 hairs from baseline (26.3% decline in hair density) measured in the target area at 5 years (p < 0.001 vs. baseline). Similarly, visible progression of scalp hair loss was demonstrated by global photographic assessment, with 75% of placebo patients rated as worsened from baseline at 5 years. We found that scalp hair loss continued in a progressive manner over a 5-year period in placebo-treated men with AGA.     

A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men

BACKGROUND: Topical minoxidil solution 2% stimulates new hair growth and helps stop the loss of hair in individuals with androgenetic alopecia (AGA). Results can be variable, and historical experience suggests that higher concentrations of topical minoxidil may enhance efficacy. OBJECTIVE: The purpose of this 48-week, double-blind, placebo-controlled, randomized, multicenter trial was to compare 5% topical minoxidil with 2% topical minoxidil and placebo in the treatment of men with AGA. METHODS: A total of 393 men (18-49 years old) with AGA applied 5% topical minoxidil solution (n = 157), 2% topical minoxidil solution (n = 158), or placebo (vehicle for 5% solution; n = 78) twice daily. Efficacy was evaluated by scalp target area hair counts and patient and investigator assessments of change in scalp coverage and benefit of treatment. RESULTS: After 48 weeks of therapy, 5% topical minoxidil was significantly superior to 2% topical minoxidil and placebo in terms of change from baseline in nonvellus hair count, patient rating of scalp coverage and treatment benefit, and investigator rating of scalp coverage. Hair count data indicate that response to treatment occurred earlier with 5% compared with 2% topical minoxidil. Additionally, data from a patient questionnaire on quality of life, global benefit, hair growth, and hair styling demonstrated that 5% topical minoxidil helped improve patients' psychosocial perceptions of hair loss. An increased occurrence of pruritus and local irritation was observed with 5% topical minoxidil compared with 2% topical minoxidil. CONCLUSION: In men with AGA, 5% topical minoxidil was clearly superior to 2% topical minoxidil and placebo in increasing hair regrowth, and the magnitude of its effect was marked (45% more hair regrowth than 2% topical minoxidil at week 48). Men who used 5% topical minoxidil also had an earlier response to treatment than those who used 2% topical minoxidil. Psychosocial perceptions of hair loss in men with AGA were also improved. Topical minoxidil (5% and 2%) was well tolerated by the men in this trial without evidence of systemic effects.     

Phototrichogram findings in women with androgenetic alopecia

BACKGROUND/PURPOSE: Androgenetic alopecia (AGA) in women is characterized by diffuse thinning in the frontal and parietal areas of the scalp; preservation of the frontal hairline is norm. Hair over the occipital scalp is preserved. The purpose of this work was to investigate the findings of phototrichogram (PTG) of the affected and the spared areas in women with AGA and to compare them with those of healthy subjects. METHODS: Twenty-two controls and 60 untreated women with AGA (32 with Ludwig I, 28 with Ludwig II) were included in this study. Hair density, percentages of thin hair, and non-growing hair were estimated both on the midscalp and on the occiput by using PTG with digital camera attached to a dermoscope. RESULTS: In the control group, hair density was higher on the midscalp than the occiput. In AGA groups, hair density was lower on the midscalp than the occiput and percentages of thin hair and non-growing hair were higher on the midscalp than the occiput. These findings were more prominent in Ludwig II group. In the occiput there were findings mimicking the changes seen on the midscalp. These were less striking than those seen on the midscalp yet the difference between the control and Ludwig II group was statistically significant. CONCLUSION: We concluded that the hair is not equally distributed on the scalp, the occiput may be affected in females with AGA and further studies are necessary to support these findings.     

Current understanding of androgenetic alopecia. Part II: clinical aspects and treatment

The first signs of androgenetic alopecia (AGA) may start to develop with the onset of puberty. The prevalence of progressive AGA approaches 50% of Caucasian men and women beyond the age of 40; whereas in Asian, native American and African-American men the prevalence is lower and AGA is less severe. Only exceptionally laboratory tests or scalp biopsies are needed to confirm the diagnosis. Therefore the clinical assessment of AGA is largely a matter of common sense and practice. The loss of hair is often trivialised, but hair loss may have profound effects on a patient's well-being and quality of life. The treatment of AGA is obscured by myths. Many products or procedures are advertized for the treatment of AGA such as vitamins, trace elements, exotic herbs, amino acids, "soft laser", scalp massage, etc. Most of these techniques or substances have never been verified in sound clinical trials. Because of the psychosocial impact of hair loss, however, it is important to explain to patients what they may expect in terms of continuing hair loss, and that response to any therapy may be slow and may include hair regrowth or only retardation of further thinning. The aim of AGA treatment is to reverse or to stabilize the process of HF miniaturization and with this overview we summarize the present treatment modalities for both men and women.     

Physiological changes in scalp, facial and body hair after the menopause: a cross-sectional population-based study of subjective changes

Background Significant changes in scalp, facial and body hair occur after the menopause. These can have a significant negative impact on self‐esteem and are also potential markers of endocrine or metabolic diseases. Knowledge of postmenopausal hair changes is important for clinicians to distinguish between normal physiological change and those that require further medical investigation. Objectives To assess the subjective experience of scalp, facial and body hair change in a large cohort of normal postmenopausal females. Methods Postmenopausal females aged 45 years or over of northern European origin completed a questionnaire detailing scalp, facial and body hair changes following the menopause. Women with a history of thyroid disease, oophorectomy or premature menopause were excluded from the study. The Mann–Whitney U‐test and the χ² test were used to assess the correlation between scalp, facial and body hair changes with age. Results Diffuse generalized hair loss was the most common form of scalp hair loss, reported by 26% of women. Frontal hair loss was reported by 9% of women. Facial hair gain was cited by 39% of females with the chin being the most frequent site for new growth (32% of women). Body hair loss was significantly correlated with older age (P < 0·001) and was most frequent at androgen‐sensitive sites. We noted two patterns: (i) diffuse hair loss in which diffuse generalized scalp hair loss was significantly correlated with body hair loss and increasing age (P < 0·05); and (ii) frontal hair loss which was associated with higher facial hair scores and relatively younger age (P < 0·05) compared with women with diffuse hair loss. Conclusions This is the first comprehensive study of the subjective hair changes in postmenopausal women. This study demonstrates two distinct patterns of hair change relating to age, which may reflect different underlying pathophysiological mechanisms and are of relevance to the medical management of these women as well as being possible predictors of health outcomes.     

Chronic telogen effluvium: Increased scalp hair shedding in middle-aged women

Background: Diffuse loss of scalp hair is a common problem in middle-aged women. A segment of these cases represents idiopathic chronic telogen effluvium (CTE).Objective: The purpose was to establish distinctive clinical and pathologic criteria for the diagnosis of CTE to facilitate its differentiation from androgenetic alopecia (AGA) and systemic causes of chronic diffuse hair loss.Methods: A group of 355 patients (346 females, 9 males) with diffuse generalized thinning of scalp hair of unknown origin were classified as having CTE and were included in the study. Characteristically they presented with a history of hair loss with both increased shedding and thinning of abrupt onset and fluctuating course and showed diffuse thinning of hair all over the scalp, frequently accompanied by bitemporal recession. Two 4 mm punch biopsy specimens were taken mostly from the mid or posterior parietal scalp of these patients. The biopsies were performed at these same areas in 412 patients with AGA (193 male, 219 female). Similar paired biopsy specimens were also taken from 22 normal control subjects (13 males, nine females). Specimens were sectioned horizontally and vertically and were examined for terminal and velluslike (miniaturized) hairs, follicular stelae, follicular units, and perifollicular inflammation and fibrosis.Results: In horizontal sections of 4 mm punch biopsy specimens from patients with CTE the average number of hairs was 39, the terminal/velluslike hair ratio was 9:1, 89% of the terminal hairs were in anagen, and 11% were in telogen. In AGA these values were 35, 1.9:1, 83.2%, and 16.8%, respectively, and in normal control subjects 40, 7:1, 93.5%, and 6.5%, respectively. Significant degrees of inflammation and fibrosis were present in only 10% to 12% of cases of CTE and normal controls, but occurred in 37% of cases of AGA. CTE ran a prolonged and fluctuating course in many patients.Conclusion: CTE, which usually affects 30- to 60-year-old women, starts abruptly with or without a recognizable initiating factor. It may be distinguished from classic acute telogen effluvium by its long fluctuating course and from AGA by its clinical and histologic findings.     

The effect of eflornithine 13.9% cream on the bother and discomfort due to hirsutism

Although unwanted facial hair often leads to anxiety and avoidance of social situations, evaluation of treatment outcomes in clinical trials has relied largely on measures external to the patient such as the extent of hair growth or an expert physician's assessment, neglecting to include patient reported outcomes (PRO). To assess the level of bother caused by a dermatological condition (hirsutism) and changes brought on by treatment, the instrument ESTEEM was developed by expanding the Bother Assessment in Skin Conditions (BASC) scale to six questions to cover the discomfort felt in four social situations and bother due to removing facial hair. Each question elicits responses on a visual analog scale. Women participating in two randomized clinical trials evaluated a new treatment (eflornithine 13.9% cream). Analyses examined the level of bother at each visit, the changes with treatment, the correlations with the Physician's Global Assessment, and the effect size. Hirsutism bothers patients considerably. The mean for overall bother was 89% and the mean discomfort in social situations exceeded 80% in nearly all cases. Treatment led to significant reductions in bother on all six items with effect sizes ranging from 0.46 to 1.62. Eflornithine is an effective treatment for unwanted facial hair in women, as reported by the patients. ESTEEM addresses the specific concerns of women with hirsutism.     

Changes in hair weight and hair count in men with androgenetic alopecia after treatment with finasteride, 1 mg, daily

BACKGROUND: Finasteride, a type II 5alpha-reductase inhibitor, reduces scalp and serum dihydrotestosterone and has been shown to be effective in men with androgenetic alopecia (AGA). OBJECTIVE: The purpose of this study was to determine the effect of finasteride on scalp hair weight in men with AGA. METHODS: Sixty-six men with AGA received finasteride, 1 mg/d, or placebo in a 48-week study, and 49 men continued in a 48-week extension. Efficacy was assessed by scalp hair weights and hair counts. RESULTS: As expected, hair counts improved with finasteride (net mean percent change +/- SE [95% CI] compared with placebo = 9.2% +/- 2.8% [3.8, 14.6] and 15.4% +/- 3.2% [9.1, 21.7] at 48 and 96 weeks, respectively; P <.01 for both time points), and net improvements in hair weight were greater (25.6% +/- 3.6% [18.5, 32.7] and 35.8% +/- 4.6% [26.7, 44.8] at 48 and 96 weeks, respectively; P <.001 for both time points). Finasteride was generally well tolerated. CONCLUSION: In this study, finasteride, 1 mg, increased hair weight in men with AGA. Hair weight increased to a larger extent than hair count, implying that factors other than the number of hairs, such as increased growth rate (length) and thickness of hairs, contribute to the beneficial effects of finasteride in treated men.     

TrichoScan. A new instrument for digital hair analysis

BACKGROUND/OBJECTIVE: Hair loss or hair thinning is a common complaint in clinical dermatology. Patients seeking advice for hair loss are not necessarily bald. In addition, the effects of therapy are hard to measure. Consequently, there is a need for a sensitive tool to monitor hair loss and treatment response. Such a method must be able to analyze the biological parameters of hair growth, which are: 1: hair density (n/cm(2)), 2: hair diameter (micrometer), 3: hair growth rate (mm/day) and 4: anagen/telogen ratio. PATIENTS/METHODS: We present the TrichoScan as a method which combines epiluminescence microscopy (ELM) with automatic digital image analysis for the measurement of human, and potentially animal hair, in situ. The TrichoScan is able to analyze all biological parameters of hair growth with a so called intraclass correlation of approximately 91% within the same operator and an intraclass correlation of approximately 97% for different operators. RESULTS: The application of the technique is demonstrated by comparison of the hair parameters in individuals without apparent hair loss with men with untreated AGA and men after treatment with finasteride (1 mg/day), and women who were treated with minoxidil. We were able to detect a significant increase in hair counts and cumulative hair thickness 3 and 6 months after treatment. CONCLUSION: The advantage of the TrichoScan is that it can be used for clinical studies to compare placebo versus treatment or to compare different hair growth promoting substances, it can be used for studying AGA or other forms of diffuse hair loss, and it can be adopted to study the effect of drugs or laser treatment on hypertrichosis or hirsutism.     

An X-linked gene involved in androgenetic alopecia: a lesson to be learned from adrenoleukodystrophy

BACKGROUND: Adrenoleukodystrophy (ALD), including its adult variant adrenomyeloneuropathy (AMN), is an X-linked recessive trait characterized by progressive demyelinization of the nervous system. The gene defect involves a peroxisomal transporter protein, resulting in accumulation of very-long-chain fatty acids in the brain and other organs such as the adrenal glands. Affected men show various endocrine disorders. Moreover, disturbances of hair growth are frequently mentioned in reports on ALD/AMN. OBJECTIVE: This study was performed to delineate further the hair status and type of hair loss in men with AMN. METHODS: We examined and documented the status of hair growth in 16 men suffering from AMN. A meticulous history with particular regard to hair changes was taken from all patients and their family members. RESULTS: The age of the patients varied between 27 and 62 years, their mean age was 39.8 years. Twelve men showed male-pattern androgenetic alopecia (AGA), Hamilton grades IV-VIII, 3 men had a female-pattern AGA (Ludwig grade I or II). Ten of the patients with male-pattern AGA had reached Hamilton stage VII or VIII. The remaining scalp hair was unusually scarce and thin in 11 cases, regardless of the grade of AGA. Moreover, in 10 of 16 patients the eyelids showed pronounced madarosis. The remaining body hair was found to be normal. If present, endocrine manifestations had started prior to the onset of alopecia, and in 11 of 12 patients hair loss was apparent before neurological symptoms were noted. CONCLUSION: ALD/AMN gives rise to two different types of hair loss. Firstly, affected men show diffuse hair loss involving the entire scalp and the eyelashes. Secondly, they tend to develop AGA more frequently and earlier and in a severer form. Paradoxically, pronounced AGA is present although the patients may simultaneously show some degree of hypogonadism. Hence, the X-linked ALD mutation can be taken as a well-defined gene within the polygenic spectrum of genes responsible for AGA. This may be of theoretical importance for the elucidation of the pathogenetic pathways of AGA.     

TrichoScan: combining epiluminescence microscopy with digital image analysis for the measurement of hair growth in vivo

Hair loss or hair thinning is a common complaint in clinical dermatology, and patients seeking advice for hair loss are not necessarily bald. Also the effects of treatment attempts are hard to measure. Consequently, there is a need for a sensitive tool to monitor hair loss and treatment response. Such a method must be able to analyze the biological parameters of hair growth, which are: 1: hair density (n/cm2), 2: hair diameter (mm), 3: hair growth rate (mm/day) and 4: anagen/telogen ratio. Here we present the TrichoScan as a method which combines epiluminescence microscopy (ELM) with automatic digital image analysis for the measurement of human, and potentially animal hair, in situ. The TrichoScan is able to analyze all biological parameters of hair growth with a so-called intraclass correlation of approx. ninety-one percent with the same TrichoScan operator and an intraclass correlation of approx. ninety-seven percent for different TrichoScan operators. The application of the technique is demonstrated by comparison of the hair parameters in individuals without apparent hair loss with men with untreated AGA and men after treatment with finasteride (1 mg/day), where we were able to detect a significant increase in hair counts and cumulative hair thickness 3 and 6 months after treatment. The advantage of the TrichoScan is that it can be used for clinical studies to compare placebo versus treatment or to compare different capacities of different hair growth promoting substances, it can be used for studying AGA or other forms of diffuse hair loss, and it can be adopted to study the effect of drugs or laser treatment on hypertrichosis or hirsutism.     

The presence of trichodynia in patients with telogen effluvium and androgenetic alopecia

Background Trichodynia refers to pain, discomfort, and/or paresthesia in the skin of the scalp or the hair. There may be an associated psychologic comorbidity. Although androgenetic alopecia (AGA) and telogen effluvium (TE) are different entities in terms of pathogenesis, etiology, and clinical picture, both may be influenced by psychologic stress and may be the cause of secondary stress. Aims To investigate the presence of trichodynia in patients with TE and AGA and to evaluate psychologic comorbidity in patients with trichodynia. Materials and methods A total of 248 patients (153 females, 95 males), presenting with hair loss due to either TE or AGA, were enrolled in this study. The prevalence of trichodynia in these two groups was compared with that in controls (n = 184). In addition, psychiatric evaluation was performed in 25 patients with trichodynia (13 females, 12 males) and in 25 controls (16 females, nine males) without alopecia and trichodynia by a psychiatrist; Diagnostic and Statistical Manual of Mental Disorders (DSM)IV criteria were used for the assessment. Results Trichodynia was found in 72 patients (29%) with hair loss and in six controls (3.3%; P < 0.0001); 25 of the 72 patients with trichodynia underwent psychiatric evaluation and 19 of the 25 patients were found to have psychopathologic signs (76%). In the control group, only five patients had psychopathologic signs (20%; P = 0.0004). Of those with hair loss, trichodynia was more frequent in the TE group than in the AGA group (P < 0.0071). Conclusions Trichodynia is a common symptom in patients with TE and AGA, and often coexists with psychopathologic findings, including depression, obsessive personality disorder, and anxiety.     

Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study

Background Androgens are thought to have an adverse effect on female scalp hair growth. However, our clinical experience of androgen replacement therapy in women with androgen deficiency, in which hair loss was seldom reported, led us to question this concept. Objectives To evaluate the effect of subcutaneous testosterone therapy on scalp hair growth in female patients. Methods A total of 285 women, treated for a minimum of 1 year with subcutaneous testosterone implants for symptoms of androgen deficiency, were asked to complete a survey that included questions on scalp and facial hair. Age, body mass index (BMI) and serum testosterone levels were examined. Results Out of the 285 patients, 76 (27%) reported hair thinning prior to treatment; 48 of these patients (63%) reported hair regrowth on testosterone therapy (responders). Nonresponders (i.e. no reported hair regrowth on therapy) had significantly higher BMIs than responders (P = 0·05). Baseline serum testosterone levels were significantly lower in women reporting hair loss prior to therapy than in those who did not (P = 0·0001). There was no significant difference in serum testosterone levels, measured 4 weeks after testosterone implantation, between responders and nonresponders. No patient in this cohort reported scalp hair loss on testosterone therapy. A total of 262 women (92%) reported some increase in facial hair growth. Conclusions Subcutaneous testosterone therapy was found to have a beneficial effect on scalp hair growth in female patients treated for symptoms of androgen deficiency. We propose this is due to an anabolic effect of testosterone on hair growth. The fact that no subject complained of hair loss as a result of treatment casts doubt on the presumed role of testosterone in driving female scalp hair loss. These results need to be confirmed by formal measurements of hair growth.     

Androgen responsive genes as they affect hair growth

Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.     

Epilation with a long-pulse 1064nm Nd:YAG laser in facial hirsutism

BACKGROUND: Facial hirsutism and hypertrichosis are common problems and a methods are available to clinicians for the unwanted hair in a large number of patients. Several depilatory laser systems are now available and one of these modalities is the long-pulse Nd:YAG laser. OBJECTIVE: To evaluate the efficacy of the long-pulse Nd:YAG laser in removing unwanted facial hair. METHOD: In all, 29 patients completed their treatment course with a long-pulse (4 ms) Nd:YAG (1064 nm line) with fluences between 56 J/cm 2 and 70 J/cm 2 . The average reduction in hair density was assessed using hair count on digital photographs at removal 3, 6 and 9 months postoperatively. The hair-free interval was variety of also evaluated. RESULTS: The average reduction of in the hair count (the same diameter as the baseline for the criterion) was 43% at 3 months, 36% at 6 months, and 46% at 9 months. The hair-free interval with laser was two- to sixfold longer than with self-applied methods. No significant complications were observed in the range of skin types treated, even in the darker skin types. CONCLUSION: The long-pulse Nd:YAG laser is an effective and safe method for long lasting hair removal in all skin types. The delay in hair regrowth most likely explains patient satisfaction.     

Long-term treatment with finasteride 1 mg decreases the likelihood of developing further visible hair loss in men with androgenetic alopecia (male pattern hair loss)

There are no reports on the effects of pharmacologic treatment on the likelihood of developing further visible hair loss in men with androgenetic alopecia (AGA). Our objectives were to examine whether finasteride 1 mg treatment decreases the likelihood of developing further visible hair loss in men with AGA. We conducted an analysis of global photographic assessment data from two Phase III trials in which 1553 men with AGA received finasteride 1 mg/day or placebo for up to 5 years. Finasteride 1 mg treatment led to a 93% decrease relative to placebo in the 5-year likelihood of developing further visible hair loss (95% CI: 89-97%; p < 0.001). We conclude that, in men with AGA, treatment with finasteride 1 mg/day over 5 years led to a marked and sustained decrease in the likelihood of developing further visible hair loss.     

Brain-derived nerve factor and neurotrophins in androgenetic alopecia

Background Several growth factors and cytokines have been shown to be involved in normal hair cycling as well as in androgenetic alopecia (AGA). However, the molecular cascades in AGA downstream from androgen receptor activation are far from being fully elucidated. Objectives We sought to determine the difference in the protein expression of growth factors/cytokines in balding vs. nonbalding scalp specimens from the same individuals affected with AGA. Methods Balding and nonbalding scalp specimens were collected from four men with pattern baldness. Dermal papilla (DP) cells were isolated and cultured. Quantifying the protein expression of growth factors and cytokines expressed by these cells was performed using Quantibody^® Human Growth Factor Array‐1 (RayBiotech, Inc., Norcross, GA, U.S.A.). Results Brain‐derived nerve factor (BDNF) protein expression was upregulated by approximately 12‐fold in supernatants obtained from balding as compared with nonbalding DP cells (P < 0·001). Expression of neurotrophin‐3 and of β‐nerve growth factor was also upregulated. On the other hand, protein expression of insulin‐like growth factor‐1 and its binding proteins as well as of the vascular endothelial growth factor family were significantly downregulated in the balding scalp. Conclusions Neurotrophic factors, especially BDNF, may be important in mediating the effects of androgens on hair follicles, serving as a negative regulatory control signal. Further studies may lead to novel pharmacological interventions in AGA.