Diffuse female hair loss: are androgens necessary?

Diffuse hair loss in women is generally regarded as the female equivalent of male balding and is often referred to as female androgenetic alopecia. In this article we report the case of a young woman with hypopituitarism who presented with the clinical and histological features of female androgenetic alopecia in the absence of detectable levels of circulating androgens or other signs of postpubertal androgenization, showing that this pattern of hair loss is not necessarily androgen dependent.     

Hormone und Haarwachstum

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.     

Three percent topical minoxidil therapy for female androgenetic alopecia

Effective treatment of female androgenetic alopecia involves cessation of hair shedding and promotion of normal anagen hair growth. The topical use of hormones such as progesterone or an androgen receptor-binding drug such as spironolactone has not been associated with significant hair regrowth.¹ In contrast, the topical use of minoxidil has resulted in decreased hair shedding and hair growth promotion, particularly in men with androgenetic alopecia.² To investigate the usefulness of topical minoxidil therapy in female androgenetic alopecia, we studied the efficacy and safety of 3% topical minoxidil in 25 affected women. Results were correlated with disease extent and activity.     

Hormonal parameters in androgenetic hair loss in the male.

Alopecia in the male is considered as a genetically determined disorder. Increased local androgen metabolism and androgen receptor binding in the balding areas confirm the importance of the target organ hair follicle as regulative of androgen influences. In our study the hormonal parameters of 65 male patients with male pattern hair loss with a mean age of 24.31 years were compared with those of 58 age-matched controls. Determinations of the androgens, sex-hormone-binding globulin, the hypophyseal hormones luteinizing hormone, follicle-stimulating hormone and prolactin, 17 beta-estradiol and cortisol were performed by standard radioimmunoassay. Significant differences in serum levels of androstenedione, cortisol, 17 beta-estradiol and luteinizing hormone were noted between hair loss patients and control subjects. Suprarenal stimulation as well as hypophyseal feedback mechanisms therefore seem to be involved in male pattern alopecia.     

Hypothyroidism and hyperprolactinemia as a possible cause of androgenetic alopecia in the female

31 female patients suffering from androgentic alopecia were examined by means of the TRH test with regard to hypothyroidism and hyperprolactinemia. Before, as well as 20 and 40 minutes after, application of thyroxine releasing hormone (TRH), the serum concentrations of the hypohyseal thyroxine stimulating hormone (TSH) and prolactin (PRL) were measured by radioimmunoassay (RIA). In 7 of the patients (23%), we found increased TSH levels after stimulation with TRH--indicative of hypothyroidism. In 9 of the patients (29%), we observed increased PRL levels after TRH stimulation, indicating prolactinemia. TSH and PRL can interact with androgen metabolism at various levels. Thyroxine may influence the unbound, metabolically active testosterone via the sex hormone binding globulin (SHBG). Prolactine, which is stimulated by TRH, promotes the suprarenal cortisol and androgen production. In 48% of the patients, we found either hypothyroidism or hyperprolactinemia. This suggests that both conditions may contribute to the clinical picture of female androgenetic alopecia, as they interfere with the androgen metabolism.     

Conditions simulating androgenetic alopecia

Androgenetic alopecia is a common form of hair loss, characterized by a progressive hair follicular miniaturization, caused by androgen hormones on a genetically susceptible hair follicle, in androgenic‐dependent areas. Characteristic phenotype of androgenetic alopecia is also observed in many other hair disorders. These disorders are androgenetic‐like diseases that cause many differential diagnosis or therapeutic error problems. The objective of this review was to systematically analyse the greatest number of conditions that mimic the AGA pattern and explain their disease pathogenesis.     

Female pattern hair loss in complete androgen insensitivity syndrome

Female pattern hair loss, also known as female androgenetic alopecia, is generally regarded as an androgen‐dependent disorder representing the female counterpart of male balding. We describe female pattern hair loss occurring in a patient with complete androgen insensitivity syndrome suggesting that mechanisms other than direct androgen action contribute to this common form of hair loss in women.     

Hormonal regulation in male androgenetic alopecia—Sex hormones and beyond: Evidence from recent genetic studies

Male-pattern hair loss, also termed androgenetic alopecia (AGA), is a highly prevalent age-related condition that is characterized by a distinct pattern of hair loss from the frontotemporal and vertex regions of the scalp. The phenotype is highly heritable and hormone dependent, with androgens being the recognized critical hormonal factor. Numerous molecular genetic studies have focused on genetic variation in and around the gene that encodes the androgen receptor. More recently, however, the availability of high-throughput molecular genetic methods, novel methods of data analysis and sufficiently large sample sizes have rendered possible the systematic investigation of the contribution of other components of the androgen receptor pathway or hormonal pathways beyond the androgen receptor signalling pathways. Over the past decade, genome-wide association studies of increasingly large cohorts have enabled the genome-wide identification of genetic risk factors for AGA, and yielded unprecedented insights into the underlying pathobiology. The present review discusses some of the most intriguing genetic findings on the relevance of (sex)hormonal signalling in AGA.     

Androgenetic alopecia and hair growth promotion state of the art: Present and future

Our current knowledge of androgenetic alopecia and hair follicle metabolism and control has evolved from four phases of scientific evolution. In the first phase, which I have called the era of science, investigators made strides in understanding androgen metabolism in general and clarified the role of androgens in androgenetic alopecia in particular. This phase was followed by what I have labeled the era of antiandrogens when they were sought as the ideal and only treatment for androgenetic alopecia. Though valid, this approach has proved to be limited. The third phase of scientific progress, the era of biologic response modifiers, evolved when investigators discovered a group of unrelated drugs that promoted hair growth. These drugs have a variety of physiologic effects and may act synergistically to stimulate hair follicle growth. Finally, we are on the threshold of the fourth phase, the era of predictability, in which research efforts will focus on finding the active hair growth-promoting sites on these drug molecules, and on clarifying how these drugs, such as minoxidil, stimulate hair growth on physiologic, pharmacologic, biochemical, and molecular levels.     

A review of hormonal therapy for female pattern (androgenic) alopecia

Female pattern hair loss (female androgenetic alopecia) is a common, but puzzling, condition in women. Approximately 10 percent of pre-menopausal women show evidence of androgenetic alopecia. Age increases the incidence and 50-75 percent of women 65 years or older suffer from this condition. Only 2 percent topical mindoxidil is approved for treating female androgenetic alopecia. Reviews suggest that anti-hormonal therapy (e.g. cyproterone acetate, spironolactone) is helpful in treating female pattern alopecia in some women who have normal hormone levels. The use of hormonal therapies is most extensively studied in post-menopausal women. Several studies have suggested that cyproterone acetate with or without ethinyl estradiol and spironolactone can ameliorate female androgenetic alopecia in women with normal hormone levels, but larger controlled studies need to be done. Flutamide was found to be more effective than spironolactone or cyproterone in one study. Testosterone conversion inhibitors have been tried in post-menopausual women with normal hormone levels to treat alopecia. No study has shown that 1 mg of finasteride effectively treats female androgenetic alopecia but doses of 2.5 and 5 mg finasteride have helped some women in a few open studies. One case report notes the utility of dutasteride after finasteride failed. The role and place of anti-androgentic agents in female androgenetic alopecia in both pre and post-menopausal women remains to be fully defined. The need for effective agents is highlighted by the paucity of effective treatments and the substantial psychosocial impact of alopecia on women.     

A6. Surgical, pharmacological and dermocosmoceutical strategies to restore a functionally and aesthetically altered nail

Most adult men, and some women, will eventually have a certain degree of hair loss which is not a pathological condition, but which can create social and psychological problems. Androgenetic alopecia is the most common type of hair loss in both sexes and appears to be caused by a combination of genetic predisposition and androgen hormone. However, there are many other causes for hair loss such as poor nutrition, alopecia areata, infection, systemic disease, metabolic or genetic disorders, and baldness due to side-effects from drugs.
Treatment options include:
a) Hormone modifiers:
Androgen inhibitors (finasteride, dutasteride, spironolactone)
Oestrogen mediated
b) Surgical options:
Scalp surgery, excision of bald scalp, with or without tissue expansion, scalp flaps and hair transplantation have been the treatment for androgenetic alopecia for many years and are constantly being revised and improved.     

Female androgenic alopecia. The 3 alpha,17 beta-androstanediol glucuronide/sex hormone binding globulin ratio as a possible marker for female pattern baldness

Twenty-five women fulfilling the criteria for female alopecia, of either the male pattern baldness type or female pattern baldness type, were evaluated for hormone markers to delineate the clinical baldness patterns. Women with a marked increase in the 3 alpha,17 beta-androstanediol glucuronide/sex hormone binding globulin ratio and low serum sex hormone binding globulin were noted to have female pattern baldness. This pattern of baldness may represent hair loss from the influence of minimal androgen excess on genetically sensitive hair bulbs in the absence of other signs of maximal androgen excess, including hirsutism, acne, or virilism.     

Female androgenetic alopecia: An update

Androgenetic alopecia is an androgen dependent disorder occurring in genetically susceptible individuals. The pattern of hair loss in women differs from that of classical male pattern alopecia, being more diffuse and with retention of the frontal hair line in most cases. Characteristic histopathological changes occur but biopsy is rarely helpful in diagnosis. Although research has shown subtle alterations in the androgen status of women with androgenetic alopecia, most patients presenting with this disorder are normal endocrinologically. Anti-androgen therapy will result in some improvement in up to 50% of patients after 6 to 12 months of therapy, but in practice will usually only decrease the rate of hair loss and not result in new hair growth.     

Treatment of Female Androgenetic Alopecia With Cimetidine

Ten white women with moderate to severe androgenetic alopecia were treated with cimetidine 300 mg by mouth five times a day. Duration of therapy ranged from 1.5-9 months, with a median of 5 months. Seven patients (70%) showed good to excellent regrowth of hair. No major side effects were noted. The patients were followed up for 5 months. Cimetidine presumably has the ability to block androgen action. Cimetidine is not a first-line drug for the treatment of androgenetic alopecia in women and should be used only in selected cases.     

Sex hormone-binding globulin and saliva testosterone levels in men with androgenetic alopecia

Sex hormone binding globulin (SHBG), plasma testosterone and saliva testosterone were measured in sixty-four men with androgenetic alopecia and in forty males within the same age range without alopecia. There was a significant reduction in SHBG levels in bald men, compared with controls. Plasma testosterone levels were not raised in bald men, but their salivary testosterone levels were significantly higher than in controls.     

男性雄激素性秃发患者雄激素受体基因和5α还原酶基因多态性研究

目的 探讨华东地区汉族男性雄激素性秃发与雄激素受体基因和5α还原酶基因多态性的关系.方法 研究对象为101例男性雄激素性秃发患者和104例健康对照,抽取外周血后分离纯化出基因组DNA,采用聚合酶链反应和限制性片段长度多态性方法研究雄激素受体基因1号外显子StuⅠ限制性片段长度多态性和Ⅰ型5α还原酶(SRD5A1)和Ⅱ型5α还原酶(SRD5A2)基因多态性,微卫星扫描分析1号外显子CAG和GGC重复序列的多态性.结果 雄激素受体基因1号外显子StuⅠ限制性片段长度多态性在汉族男性雄激素性秃发患者与健康对照之间差异无统计学意义(P>0.05),雄激素受体基因的CAG重复序列多态性分布在两组之间差异无统计学意义(P=0.130),GGC重复序列多态性分布在两组之间差异有统计学意义(P=0.004);短CAG/短GGC分别在病例与对照组中占25.53%和46.88%(P=0.002),长CAG/长GGC分别占42.55%和19.79%(P=0.001).未发现SRD5A1及SRD5A2等位基因和基因型出现的频率不同(P>0.05).结论 雄激素受体基因GGC重复序列以及CAG/GGC重复序列多态性与汉族男性雄激素性秃发有明显关系.而5α还原酶基因多态性与汉族男性雄激素性秃发无明显关系.     

Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial

BACKGROUND: In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far. OBJECTIVES: To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss. METHODS: A double-blind, randomized, placebo-controlled study was conducted in 40 women suffering from diffuse alopecia or androgenetic alopecia. A 0.1% melatonin or a placebo solution was applied on the scalp once daily for 6 months and trichograms were performed to assess anagen and telogen hair rate. To monitor effects of treatment on physiological melatonin levels, blood samples were taken over the whole study period. RESULTS: Melatonin led to a significantly increased anagen hair rate in occipital hair in women with androgenetic hair loss compared with placebo (n=12; P=0.012). For frontal hair, melatonin gave a significant increase in the group with diffuse alopecia (n=28; P=0.046). The occipital hair samples of patients with diffuse alopecia and the frontal hair counts of those with androgenetic alopecia also showed an increase of anagen hair, but differences were not significant. Plasma melatonin levels increased under treatment with melatonin, but did not exceed the physiological night peak. CONCLUSIONS: To the authors' knowledge, this pilot study is the first to show that topically applied melatonin might influence hair growth in humans in vivo. The mode of action is not known, but the effect might result from an induction of anagen phase.     

The risk of coronary heart disease in men with androgenetic alopecia

BACKGROUND: The meaningful association of androgenetic alopecia and coronary heart disease has been well documented, but few studies have focused on the importance of lipid parameters, such as total cholesterol, triglycerides, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, lipoprotein (a), apolipoprotein A1 and apolipoprotein B in patients with androgenetic alopecia. OBJECTIVE: The aim of this study is to investigate the relation between androgenetic alopecia and coronary heart disease and to determine the significance of certain lipid parameters on this relationship. SUBJECTS: Forty-one men with vertex type androgenetic alopecia (study group) and 36 men, age-matched, with normal hair status (control group) were the subjects of this study. RESULTS: We found significant differences in serum lipoprotein (a) and triglyceride levels between the study and control groups (P < 0.05). Forty-seven percent of patients and 30% of controls had a lipoprotein (a) level more than 30 mg/dl higher than the level critical for atherosclerotic heart disease. CONCLUSION: Dermatologists should investigate lipid profile, especially lipoprotein (a), of patients with androgenetic alopecia and refer to a cardiologist if necessary.     

Androgenic alopecia revealing an ovarian secreting tumor

BACKGROUND: In menopausal women, rapid development of androgenetic alopecia may be associated with development of androgen-secreting tumors even in the absence of signs of virilisation. We report a case in which ovarian tumor was revealed by this condition. OBSERVATION: A 75 year-old woman menopausal from the age of 44 years had experienced hair loss over the previous three years with exacerbation over the last year. Clinical examination revealed male pattern androgenogenetic alopecia but with no signs of virilisation. Testosterone levels were 3 times the normal limit. Radiological examination confirmed the presence of an ovarian tumour and hysterectomy was performed with bilateral actomy. Histopathological examination revealed a mature cystic dysembryoma of the right ovary containing Leydig cell islets. The outcome was favourable with normalisation of hormone levels 2 months after surgery and gradual hair growth. DISCUSSION: This case involved a woman with androgenogenetic alopecia with no signs of virilisation or of hirsutism. The clinical picture was banal, and given the patient's age, there was no justification for routine endocrine investigation. Because of recent focus on androgenogenetic alopecia, testosterone levels were checked, resulting in the discovery of an ovarian tumour containing Leydig cells. In menopausal women with recent and/or severe androgenogenetic alopecia, testosterone levels should be determined in addition to ultrasensitive TSH and ferritin.     

Acquired progressive kinking of the hair: clinical features, pathological study, and follow-up of 7 patients.

BACKGROUND: Acquired progressive kinking of the hair (APKH) is a relatively rare condition, with fewer than 20 cases reported in the literature. Whether APKH is a separate entity or a variety of androgenetic alopecia is still controversial. This study reviews the clinical and pathological features and long-term follow-up of 7 patients with APKH. OBSERVATIONS: Since January 1989, we have diagnosed APKH in 7 males aged 15 to 22 years. All patients had strong family history for androgenetic alopecia. Hair kinking affected the frontotemporal region and/or the vertex where the hair appeared curly, frizzy, and lusterless. The pathological features of the affected scalp were consistent with the diagnosis of the early stages of androgenetic alopecia. In all patients, APKH evolved into androgenetic alopecia during the follow-up period. Mean follow-up was 4.5 years (range, 2-9 years). Treatment with topical minoxidil did not prevent development of hair thinning in the scalp areas affected by hair kinking. CONCLUSIONS: The term acquired progressive kinking of the hair encompasses a number of conditions characterized by acquired curling of the scalp hair. Acquired hair kinking on the androgen-dependent areas of the scalp represents a modality of onset of androgenetic alopecia associated with poor prognosis.