ArticleLiterature Review

Hormone und Haarwachstum

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

Der Zusammenhang zwischen Androgenen und androgenetischer Alopezie (AGA) sowie Hirsutismus ist gut bekannt. Entsprechend wurden erfolgreiche Therapien entwickelt, die in den Androgenmetabolismus eingreifen. Ein Zusammenhang zwischen Hormonen und Haarwachstum ist aufgrund klinischer Beobachtungen auch für Hormone jenseits des Androgenhorizontes erkennbar: Östrogen, Prolaktin, Thyroxin, Kortison, Wachstumshormon (GH), Melatonin. Bei der primären GH-Resistenz besteht dünnes Haar, umgekehrt verursacht Akromegalie Hypertrichose. Hyperprolaktinämie kann zu Haarausfall und Hirsutismus führen. Eine Teilsynchronisierung des Haarzyklus in Anagen während der Spätschwangerschaft weist auf die Östrogenwirkung hin, Aromatasehemmer führen umgekehrt zu Haarausfall. Effluvium im Kausalzusammenhang mit Schilddrüsenfunktionsstörungen ist gut belegt. Die senile Involutionsalopezie betrifft im Unterschied zur AGA die Haare diffus. Es stellt sich die Frage, ob die den Hormontherapien im Rahmen der Anti-Aging-Medizin zugrunde liegende Hypothese des Kausalzusammenhangs zwischen der altersassoziierten Reduktion zirkulierender Hormone und einer Funktionseinbuße auch für die Haare gilt.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Уровень пролактина также влияет на пилосебационный комплекс: на фазы роста волос и сальную железу, воздействуя на фолликул не только прямо, но и косвенно, через повышение содержания проандрогенов в коре надпочечников и метаболизм тканевых андрогенов [20]. Следовательно, гиперпролактинемия может быть причиной не только ДТВВ, но и АГА, а также акне и гирсутизма [21,22]. Снижение уровня пролактина плазмы крови до физиологических значений обычно приводит к нивелированию симптомов гиперандрогении. ...
Article
The review examines the key aspects of the pathogenesis of alopecia in endocrine system pathology. The role of hormones, growth factors, cytokines and other biologically active substances has been demonstrated. Alopecia is a frequent symptom that can be the result of not only gerontological, but also endocrinological problems. Therefore, time-consuming differential diagnosis is often necessary. Diagnosis is more effective if a team of specialists is involved: endocrinologist, gynecologist, andrologist, dermatologist / trichologist, and others.
... Melatonin receptors are located in epidermal keratinocytes, dermal fibroblasts and vascular endothelium [78]. Prolactin (PRL) mRNA has been found in dermis fibroblasts [79]. Receptors for insulin are present in keratinocytes and epidermal fibroblasts [80]. ...
Article
Full-text available
Hormones have attracted considerable interest in recent years due to their potential use in treatment of many diseases. Their ability to have a multidirectional effect leads to searching for new and increasingly effective drugs and therapies. Limitations in formulating drug forms containing hormones are mainly due to their low enzymatic stability, short half-life and limited bioavailability. One of the solutions may be to develop a hydrogel as a potential hormone carrier, for epidermal and transdermal application. This review discusses the main research directions in developing this drug formulation. The factors determining the action of hormones as drugs are presented. An analysis of hydrogel substrates and permeation enhancers that have the potential to enhance the efficacy of hormones applied to the skin is reviewed.
... DHT (26) and inhibits 5a-reductase 1 enzyme activity in pilosebaceous unit, thereby reducing the effect of DHT, which is a therapeutic paradox (27). The GHRH antagonists have been shown to reduce the PV directly acting on truncated receptor splice variant without involving the testosterone-DHT pathway (28). ...
Article
Full-text available
Disorders of the prostate gland are more prevalent in patients with acromegaly. GH-insulin-like growth factor 1 (IGF1) axis plays an additive role in prostatic growth and development. To correlate the structural and histopathological changes of the prostate and prostatic symptoms with GH/IGF1 in patients with acromegaly. Case-control study, from January 2012 to November 2013. Tertiary referral centre university hospital in Northern India. Fifty-three men with acromegaly and 50 healthy men matched for age and BMI. International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, dimensions of the prostate on trans-rectal ultrasonography, parameters on uroflowmetry, and immunopositivity with anti-IGF1 antibody in prostatic tissue biopsies. Despite low serum testosterone levels (8.9 nmol/l vs 14.3 nmol/l, acromegaly vs control), patients with acromegaly had marginally higher IPSS, PSA levels, and grades of enlarged prostate and obstructive features on uroflowmetry compared with controls. Dimensions of the prostate on ultrasonography were also significantly higher in patients. These changes were present irrespective of age, current gonadal status, and disease activity. Evidence of prostatic hyperplasia on biopsy was seen in six of 14 patients (42.8%) who underwent prostatic biopsy while it was absent in the controls. Immunohistochemistry with anti-IGF1 antibody showed moderate positivity in all the 14 patients who underwent biopsy with benign prostatic hyperplasia, compared with mild positivity in 21% of controls. Similarly, 14 control patients with prostatic malignancies showed variable positivity, four patients had strong, two each had mild and moderate positivity, while six were negative. In patients with acromegaly, there is a higher frequency of structural changes in the prostate, along with greater prostatic volume and obstructive features, compared with healthy controls, irrespective of age, gonadal status, and disease activity. © 2015 European Society of Endocrinology.
Chapter
Iodine is a chemical element with symbol I, atomic number 53. It is an essential element for life and is the heaviest trace element commonly needed by living organisms. It is required for the synthesis of the growth-regulating thyroid hormones triiodothyronine and thyroxine, named T3 and T4, respectively, after their number of iodine atoms [1].
Chapter
Cysteine is a sulfur-containing, α-amino acid with the chemical formula O2CCH(NH2)CH2SH. Cysteine is unique amongst the 20 natural amino acids as it contains a thiol group. It is classified as a conditionally non-essential amino acid since the human body can naturally synthesize it [1, 2]. Like other amino acids, cysteine has an amphoteric character and is extensively used as an additive in the food industry, mainly in bakery, in the production of flavors, and as a processing aid [3]. When used as a food additive, it is labeled as E920 [4].
Chapter
Female Pattern Hair Loss (FPHL) is by far the most common cause of hair loss affecting otherwise healthy women. For decades it has been considered the female “counterpart” of male AGA despite weaker androgenic parameters than AGA since most women with FPHL do not have an underlying hormonal abnormality; recent research shows that AGA and FPHL are entirely separate entities.
Chapter
The physiologic function of hair follicles, hair growth, circularity, and hair loss do not depend solely on the actions of androgens but are coordinated by additional hormonal parameters through complex physiological mechanisms.
Chapter
The skin is a target-organ for systemic and local reactions to stress, and hair loss may indeed occur after acutely stressful conditions, such as trauma and severe disease.
Article
Background: Chemotherapy-induced alopecia (CIA) is probably one of the most shocking aspects for oncological patients and underestimated by physicians. Among hair loss risk factors, there are treatment-related aspects such as drug dose, administration regimen, and exposure to X-rays, but also patient-related characteristics. To the best of our knowledge, no guidelines are available about CIA management. Aims and methods: With this study, based on literature background and our clinical experience, we would like to propose a list of actions in order to estimate the risk of hair loss before starting chemotherapy and to manage this condition before, during, and after drug administration and to create a sort of practical guide for dermatologists and oncologists. Results and conclusion: There is an urgent need for prospective studies to clarify the mechanistic basis of alopecia associated with these drugs and consequently to design evidence-based management strategies.
Chapter
Hair loss and scalp lesions may accompany several systemic disorders, such as metabolic abnormalities, endocrine conditions, autoimmune diseases, nutritional deficiencies, internal malignancy, and hematologic diseases. Hair problems may be the initial complaint causing patients to seek medical assistance. Thus, when performing trichoscopy, dermatologists should maintain a high index of suspicion when patients present with unexplained trichologic complaints.
Article
Patients suffering from hair loss or undesirable excessive hair growth are a challenge for dermatologists because the pathogenesis of most hair diseases is not well understood and therapeutic options are limited. This particularly holds true for genetic hair disorders, in which all current treatment attempts are unsuccessful. Furthermore, these diseases also pose a diagnostic challenge due to a broad range of clinical and genetic heterogeneity. However, the enormous progress in molecular biology over the past 20 years, in particular the availability of different new techniques such as whole exome and genome sequencing, has enabled us to elucidate the genetic basis of most monogenic hair disorders, given the availability of suitable index patients and families as well as adequate technical equipment and sufficient financial resources. In this review we provide an update on clinical and genetic aspects of selected monogenic and polygenic hair diseases manifesting with hypertrichosis and hypotrichosis.
Article
Full-text available
Androgenetic alopecia (AGA) is a well-characterized type of progressive hair loss commonly seen in men, with different prevalences in different ethnic populations. It is generally considered to be a polygenic heritable trait. Several susceptibility genes/loci, such as AR/EDA2R, HDAC9 and 20p11, have been identified as being involved in its development in European populations. In this study, we aim to validate whether these loci are also associated with AGA in the Chinese Han population. We genotyped 16 previously reported single nucleotide polymorphisms (SNPs) with 445 AGA cases and 546 healthy controls using the Sequenom iPlex platform. The trend test was used to evaluate the association between these loci and AGA in the Chinese Han population. Conservatively accounting for multiple testing by the Bonferroni correction, the threshold for statistical significance was P ≤3.13×10(-3). We identified that 5 SNPs at 20p11 were significantly associated with AGA in the Chinese Han population (1.84×10(-11)≤P≤2.10×10(-6)). This study validated, for the first time, that 20p11 also confers risk for AGA in the Chinese Han population and implicated the potential common genetic factors for AGA shared by both Chinese and European populations.
Article
Full-text available
Background: In an earlier study, we identified an association between hair relaxer-induced alopecia and decreased zinc levels. This study hopes to identify if age at first exposure to hair relaxer plays a role in the development of alopecia in the small percentage of women of African descent who use hair-relaxing products for hair-straightening purposes and develop lingering, nonresolving alopecia. Methods: Two categories of subjects were recruited for the study. These groups—Group A and Group B—commenced use of hair relaxer in the second and third or fourth decade of life, respectively. Group C which served as the control group consisted of women who had used relaxer but did not manifest alopecia. Renal and hepatic indices as well as micronutrient levels were estimated in serum samples taken from these subjects. Data obtained were subjected to statistical analysis using Student t test, analysis of variance, and Pearson correlation coefficient. Results: Of all the micronutrients, only zinc level was significantly decreased in the two categories of alopecia subjects compared with controls, and when the zinc levels of the two groups were compared, they were not significantly different. Age in association with an alteration in serum zinc status seemed to have played an independent or combined role as an etiologic factor in hair relaxer-induced alopecia in Group B subjects, as a positive correlation (r = 0.631; p = 0.012) was observed between age and duration of alopecia; alopecia also commenced much earlier in the course of hair relaxer application in Group B compared with Group A. Conclusion: This is probably an indication that early exposure may confer some forms of protection even in zinc-deficient individuals. Moreover, an assessment of serum zinc level in users of hair relaxer may be encouraged even before initial contact with this agent, such that women at risk could be advised to take zinc supplements.
Article
Objective: Scalp hair loss is often encountered in clinical practice in Japan after successful surgery for acromegaly. However, this intriguing issue has not been addressed in the literature. The aim of this study was to examine scalp hair loss after surgery for acromegaly. Methods: Postoperative scalp hair loss was surveyed using a mail-back questionnaire given to 511 patients undergoing primary surgery for acromegaly, 484 of whom constitute the patient pool in this study. Results: Of the 484 patients, 263 (54%) patients noticed varying degrees of hair loss between 3 and 6 months after surgery [the degree of alopecia was minimal in 50 patients (10%), moderate in 117 patients (24%), and severe in 96 patients (20%)], although postoperative hair loss was noticed only in six (3·6%) of 167 patients with nonfunctioning adenomas. Postoperative hair loss was significantly more common in female patients, cured patients and patients with severe postoperative growth hormone deficiency. Among those 263 patients, full recovery was reported by 85 patients (32%), incomplete recovery by 88 patients (34%), and hardly any recovery by 90 patients (34%). A lack of hair recovery was significantly more common in male patients or in patients with severe hair loss after surgery. Conclusions: This, the first large-scale, single-centre, clinical study to shed light on the issue of postoperative hair loss after surgery for acromegaly, shows that it is important to prospectively inform patients that varying degrees of hair loss occur in a large number of acromegalic patients, especially after successful surgery.
Article
Full-text available
In the literature of the past 30 years there are only some publications concerned with hair loss and hyperprolactinemia in women. Therefore, the relevance of hyperprolactinemia was evaluated in 40 women with diffuse alopecia. Hair loss was assessed by clinical appearance and the pluck trichogram. 82.5% of the female patients had diffuse hair loss and 17.5% had androgenetic alopecia. The highest prolactin values measured were 1390 ng/ml and 255 ng/ml. Six patients had values between 150–80.4 ng/ml and 10 between 79.1–51.7 ng/ml. All others had prolactin values below 50 ng/ml. Fifteen untreated patients with elevated prolactin levels could be followed up. Without any prolactin-inhibiting drugs, reductions and normalizations beside moderate fluctuations could be detected. Thyroid-specific diagnostics showed in 95% of the patients a normal thyroid function. 2.5% had a slight hyperthyreoidism and 2.5% had a slight hypothyreoidism. No female patient had clinical signs of androgenization and the determined androgens testosterone, androstendione and dihydroepiandrostendione were in the normal range. According to these results, moderate elevated prolactin levels in association with diffuse or androgenetic hair loss can be neglected as causative for the hair loss, because there is no evidence that they have an influence to the pattern, the extent or the duration of the hair loss. These results are supported by investigations of other authors who described only in high doses of prolactin an inhibiting effect on human hair follicles in vitro. Nevertheless, moderate constantly elevated prolactin levels should induce further diagnostics to exclude a prolactin-producing tumor of the pituitary gland.
Article
In recent years there has been increasing awareness that the hair follicles and their associated pilosebaceous structures may act as significant permeation pathways and/or reservoirs for topically applied drugs. This has implications in terms of dermatological therapy for acne, hirsutism, alopecias or certain skin cancers as well as systemic drug delivery. As the processes modulating follicular drug penetration are poorly understood at present, there is an emergent need for methodologies that can quantify follicular drug penetration and deposition. So far, a review article specifically dedicated to these methodological aspects has not yet been written. This paper reviews the available quantitative follicular methodologies that have been developed over the years, describing the advantages and disadvantages of each approach. This review covers comparative techniques that are based on measuring drug flux through 'follicle-free' and 'follicle-containing' integuments, the skin sandwich, differential stripping and optical imaging-based technologies. Techniques for measuring drug-sebum interactions are also discussed. The reader will develop an understanding of the complexities involved in quantifying drug delivery through follicles and pilosebaceous units. The Expert opinion section will give the reader insights into how more broad-ranging future research could allow identification of the most useful methods for quantifying follicular drug transport. This is still a poorly understood field. It clearly warrants much larger scale studies than have been performed so far involving multiple techniques and multiple drugs.
Article
Full-text available
Pituitary thyroid-stimulating hormone (TSH) regulates thyroid hormone synthesis via receptors (TSH-R) expressed on thyroid epithelial cells. As the hair follicle (HF) is uniquely hormone-sensitive and, hypothyroidism with its associated, increased TSH serum levels clinically can lead to hair loss, we asked whether human HFs are a direct target for TSH. Here, we report that normal human scalp skin and microdissected human HFs express TSH-R mRNA. TSH-R-like immunoreactivity is limited to the mesenchymal skin compartments in situ. TSH may alter HF mesenchymal functions, as it upregulates alpha-smooth muscle actin expression in HF fibroblasts. TSH-R stimulation by its natural ligand in organ culture changes the expression of several genes of human scalp HFs (for example keratin K5), upregulates the transcription of classical TSH target genes and enhances cAMP production. Although the functional role of TSH in human HF biology awaits further dissection, these findings document that intracutaneous TSH-Rs are fully functional in situ and that HFs of female individuals are direct targets for nonclassical, extrathyroidal TSH bioregulation. This suggests that organ-cultured scalp HFs provide an instructive and physiologically relevant human model for exploring nonclassical functions of TSH, in and beyond the skin.
Article
Full-text available
One hundred women who presented with diffuse alopecia, were quantitatively evaluated for hair variables and compared with 20 controls. Fifty were selected for biochemical and haematological investigations, 44 of whom also underwent endocrine evaluation. Compared to controls, significant changes in hair values were found in the frontal area of all subjects, while 84% had significant changes in the occipital area. A biphasic distribution of hair diameter was evident in subjects who had percentages of vellus hair and telogen hair less than or equal to 30 mm in length that were above the control ranges. No significant difference between the mean hormonal values of women with diffuse alopecia and controls could be found. No correlation between hair values and individual or combined hormonal levels could be established. In 18 subjects (40.9%) hormonal values were within the control ranges and these apparently normal findings were often associated with adverse hair profiles. A raised dihydrotestosterone was found in 13 subjects (29.5%) and was the most frequently elevated androgenic finding. Seventeen (34.0%) had changes in iron metabolism, while in 36 (72.0%) serum ferritin levels were below the lowest control value. All had a decrease in the percentage of hair in the anagen growth phase compared to controls. The hair changes were similar to those observed in genetic hair loss in men, a proven androgen-dependent condition. We propose that diffuse androgen-dependent alopecia is the appropriate name to describe this condition in these women.
Article
Full-text available
Androgenetic alopecia (AGA), a hereditary disorder that involves the progressive thinning of hair in a defined pattern, is driven by androgens. The hair follicle dermal papilla (DP) expresses androgen receptors (AR) and plays an important role in the control of normal hair growth. In AGA, it has been proposed that the inhibitory actions of androgens are mediated via the DP although the molecular nature of these interactions is poorly understood. To investigate mechanisms of AGA, we cultured DP cells (DPC) from balding and non-balding scalp and confirmed previous reports that balding DPC grow slower in vitro than non-balding DPC. Loss of proliferative capacity of balding DPC was associated with changes in cell morphology, expression of senescence-associated beta-galactosidase, as well as decreased expression of proliferating cell nuclear antigen and Bmi-1; upregulation of p16(INK4a)/pRb and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase catalase, ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. Premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPC are sensitive to environmental stress and identifies alternative pathways that could lead to novel therapeutic strategies for treatment of AGA.
Chapter
Androgenetic (AGA) and senescent alopecia (SA) are common nonscarring hair loss disorders. The histopathology of both disorders involves follicular downsizing, and yet, they differ in the age of onset, pattern of hair loss, and hormonal involvement. We compared gene expression profiles of scalp biopsies from age-matched men with AGA, SA, and normal controls. Our data suggest that follicular downsizing in AGA is associated with altered expression of genes required for hair follicle cycling. In stark contrast, the transcriptional profile of SA reveals mitochondrial dysfunction and oxidative stress response, which are characteristic of aging tissues. These marked differences between AGA and SA suggest that they are two distinct disorders that present diverse mechanisms for a final common phenotype of follicular downsizing.
Article
Die androgenetische Alopezie (a. A.) ist relativ häufig; bis zu 79% aller Frauen klagen zumindest über unterschiedliche Grade von schubweise auftretendem diffusen Haarverlust im zentroparietalen und/oder frontalen Scheitelbereich. Die a. A. wird bei entsprechender genetischer Disposition durch Androgene, die über einen längeren Zeitraum an der Haarwurzelzelle wirken, verursacht. Eine entsprechende Hyperandrogenämie läßt sich jedoch bei Patientinnen mit a. A. häufig nicht nachweisen. 125 Frauen mit einer klinisch typischen a. A. wurden prospektiv und unter standardisierten Bedingungen einer umfangreichen differentialdiagnostischen Abklärung unterzogen. Das Alter der Patientinnen schwankte von 18 bis 68 Jahren (MW ± SD: 35,4 ± 11,6). Bei 69 Patientinnen wurden Blutungsanomalien wie Menorrhagien sowie Hyper- und Polymenorrhoen registriert. Der tägliche Haarverlust lag zwischen 50 und 400 Haaren (124 ± 125). Andere Androgenisierungserscheinungen wie Seborrhö (n = 85), Akne (n = 52) und Hirsutismus (n = 28) konnten häufig beobachtet werden. Es wurden radioimmunologisch folgende Parameter bestimmt: Gesamtes und freies Testosteron (T und FT), Dihydro-T (DHT). DHEA-Sulfat (DS). Δ4-Androstendion (A). 17α-Hydroxyprogesteron (17P). Cortisol (F). Progesteron (P). 17β-Östradiol (E2), Sexualsteroid bindendes Globulin (SHBG), Prolaktin (PRL), Thyreoidea-stimulierendes Hormon (TSH). Ferritin (Fe), Vitamin B12 (B12) und Folat (Fo). Die FT-Konzentrationen wurden zusätzlich durch eine Equilibriumsmethode überprüft. Die Wertigkeit der einzelnen Untersuchungsverfahren wird ausführlich diskutiert. Außerdem wurde bei allen Patientinnen ein kombinierter ACTH-TRH-Test durchgeführt. Unter Berücksichtigung einer klinisch relevanten Grauzone ließen sich bei 26,4% der Patientinnen ein, bei 67,2% der Patientinnen zwei und mehr pathologische Befunde ermitteln. Nur bei 6,4% der Patientinnen lagen alle Parameter im Normbereieh. Die Frequenz pathologischer Parameter war wie folgt: FT in % = 52%, Fe = 42%, PRL - 34%, E2 = 34%, FT in pg = 29%, DHT = 28%, SHBG = 26%, TSH = 20,8%, DS = 19%, T = 14%, 17P = 11%, Fo = 7%, A = 6%, F = 6%, B12 = 5%. Sowohl im Gruppen- wie im Einzelfallvergleich bestanden signifikant Zusammenhänge zwischen: (1) der Höhe der diversen Androgen-, PRL- und TSH-Spiegel und den (2) Meßwerten für E2, SHBG und FT wie auch weiterhin zwischen diesen und (3) bestimmten Blutungsanomalien (Stärke, Dauer, Intervall) und schließlich zwischen diesen Blutungsstörungen und (4) dem Ferritinmangel. Die Therapie hatte eine Normalisierung des gestörten Östrogen-Androgen-Gleichgewichts zum Ziel. Unter Benutzung von Antiandrogenen (in niedriger Dosierung), Östrogenen, Prolaktinhemmern, Kortikoiden, Eisen-II-Präparaten sowie durch östrogenhaltige Haarwässer konnte bei 74 von 104 behandelten Frauen ein Stopp des Haarausfalls und bei 16 Frauen ein Nachwachsen der Haare erreicht werden. Bei 14 Frauen fehlte ein therapeutischer Effekt.
Article
Background: In a previous study, we reported a significant and dose-dependent suppression of UV-induced erythema in human skin by a topically applied melatonin preparation. Objective: The present double-blind randomized study was designed to examine the influence of the application time point of topical melatonin on this antierythema effect. Methods: Defined small areas on the lower back of 20 volunteers were treated with 0.6 mg/cm2 melatonin dissolved in a nanocolloid gel carrier either 15 min before or 1 30 or 240 min after UV irradiation with twice the individual minimal erythema dose delivered by a Multiport Solar UV Simulator (UVA and UVB). The erythemata induced were evaluated by visual scoring and chromametry 24 h after irradiation. Results: Treatment of the skin with melatonin 15 min before UV irradiation proved to almost completely suppress the development of an UV-induced erythema. In contrast, no significant protective effects of melatonin were observed when it was applied after UV irradiation. Conclusion: Topically applied melatonin has a clear-cut protective effect against UV-induced erythema. Free radical scavenging of UV-generated hydroxyl radicals and interference with the arachidonic acid metabolism are possible mechanisms of the melatonin action.
Article
Die androgenetische Alopezie ist bei Frauen und Mnnern die hufigste Form von Haarverlust. Wenngleich sich der Haarausfall bei Frau und Mann klinisch unterschiedlich manifestiert, so sind dennoch die zugrunde liegenden, zur Alopezie fhrenden Pathomechanismen dieselben. Es kann davon ausgegangen werden, dass aufgrund genetischer Prgung bestimmte Haarfollikel am Kapillitium eine verstrkte Sensitivitt gegenber Androgenen aufweisen. Die Forschungsergebnisse der letzten Jahre haben eine Vielzahl pathophysiologisch, diagnostisch und therapeutisch bedeutsamer Erkenntnisse hervorgebracht, deren klinisch relevante Aspekte und Neuerungen in dieser bersicht dargestellt werden.Androgenetic alopecia is the most common form of hair loss in men and women. Although the clinical manifestations are different in men and women, the pathogenetic pathways leading to this type of hair loss are similar in both sexes. In short genetically predestined hair follicles show an increased sensitivity to androgens. In recent years, much new data concerning the pathophysiology, management and therapy of androgenetic alopecia has been gathered. This article gives a critical overview of these new findings and assesses their practical relevance.
Article
A thyroid hormone receptor beta subtype-selective thyromimetic 5 was found to be efficacious in both mouse and monkey hair growth models after topical applications. It penetrates the skin according to the test in human cadaver skin mounted onto Franz diffusion chambers. The serum drug level of 5 is below the limit of quantification during tests in the bald stump-tailed macaques (Macaca arctoides). It is tested negative in the 3T3 neutral red uptake (NRU) phototoxicity test, indicating a low risk for causing photo-irritation. It is also rapidly metabolized according to the PK data, thus the systemic exposure is limited.
Article
A distinctive form of hereditary male pseudohermaphroditism is described in 24 members of 13 families in an isolated village of the Dominican Republic with a population of 4,300. The affected males are born with ambiguous external genitalia and in the past they were raised as girls. At puberty they develop typical male phenotype and male psychosexual orientation. Their karyotype is 46 XY. The condition is due to deficiency of Δ4 5α reductase which results in diminished transformation of testosterone and other deoxysteroids to 5α metabolites. The biochemical defect is inherited in an autosomal recessive fashion. Both male and female homozygotes are found but the biochemical defect is expressed only in males. Obligate heterozygotes are phenotypically normal but have a reductase deficiency, intermediate between that of normal and affected. The isolation of the village and demonstration of common ancestry in pedigrees suggests that the increase in gene frequency is a consequence of founder effects. (Myrianthopoulos - Bethesda, Md.)
Article
In both, 6 hyperthyroid and 6 hypothyroid patients as well as 10 healthy volunteers, cell cycle kinetics of dissected anagen scalp hair bulbs were determined by means of DNA flow cytometry (DNA-FCM). Compared with the healthy control group in patients with thyroid disorders striking differences of cell kinetic data were evaluated. In hyperthyroidism a significant increase (30%) and in hypothyroidism a significant decrease (15%) of S and G2+M phase cell percentages was found. The proliferation index (S+G2+M %) calculated revealed similar results. A correlation between the height of S phase percentages and plasma T3 levels was recognizable but could not be proven statistically. By means of DNA-FCM the study demonstrates for the first time the influence of thyroid hormones on in vivo cell cycle kinetics of human scalp hair bulbs.
Article
In male pseudohermaphrodites born with ambiguity of the external genitalia but with marked virilization at puberty, biochemical evaluation reveals a marked decrease in plasma dihydrotestosterone secondary to a decrease in steroid 5α-reductase activity. In utero the decrease in dihydrotestosterone results in incomplete masculinization of the external genitalia. Inheritance is autosomal recessive.
Article
A broad range of hormones was determined in males and females with androgenic hair loss (AH). The androgens testosterone, androstenedione, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and sex hormone binding globulin were evaluated in 65 male and 46 female patients. Besides estradiol (E2), cortisol (F), and the hypophyseal hormones LH, FSH, and prolactin (PRL) were investigated. Hormone levels were compared with those of 58 age-matched male and 45 female controls. In 38 of the 46 female AH patients, hypophyseal function was moreover evaluated by the 'TRH test', which detects slight, secondary hypothyroidism and/or hyperprolactinemia. Our findings showed a significant elevation of F in both male and female AH patients compared to controls, pointing to the suprarenes as a contributing factor in AH. This is confirmed by the observation of exacerbated AH in periods of increased stress. Concerning specifically male androgens, a significant elevation of androstenedione was noted. The mainly peripheral activity of this hormone and elevated E2 levels in males stress the importance of androgen metabolism especially at the peripheral level. Additional TRH tests in females demonstrated significant hypophyseal hypothyroidism. Multilayered interaction between thyroid hormones and androgens may contribute to the development of AH in hyperthyroid patients. Another significant finding was elevated PRL after TRH stimulation. Thus, the androgen-stimulating effect of PRL may also play a role in female AH. Our findings show multilayered hormonal influences in AH. Broad-range hormone determination demonstrated a differentiated hormonal situation in this disorder.
Article
It has been demonstrated by various workers in the past that glucocorticosteroids block hair growth. Using the mouse model for studying hair growth induction we reexamined the effect of topically applied steroids on hair growth to establish at what stage the steroid block acts. In accord with studies by others, we found that these steroids block hair growth at the point of anagen initiation, but that once the steroid applications are stopped, hair growth starts. Since steroid withdrawal alone did not induce hair growth, it is clear that these steroids do not block, either spontaneous or manipulated, hair growth induction, but they do block, the apparent next step, i.e., hair formation. Moreover, since hair growth could be induced even while the animals were being treated with the steroid, the induction step appears independent of the steroid block. These studies and those of others lead us to conclude that these steroids block the expression of hair-forming genes, but do not interfere with the signal(s) that initiates those genes. This system appears to be ideal for identifying the signals (perhaps, genes) responsible for initiating hair growth.
Article
In this study, 12 women and 12 men, ages 18-33 y, with androgenetic alopecia were selected for biopsies from frontal and occipital scalp sites. The androgen receptor, type I and II 5alpha-reductase, cytochrome P-450-aromatase enzyme were measured and analyzed in hair follicles from these scalp biopsies. Findings revealed that both women and men have higher levels of receptors and 5alpha-reductase type I and II in frontal hair follices than in occipital follicles, whereas higher levels of aromatase were found in their occipital follicles. There are marked quantitative differences in levels of androgen receptors and the three enzymes, which we find to be primarily in the outer root sheath of the hair follicles in the two genders. Androgen receptor content in female frontal hair follicles was approximately 40% lower than in male frontal hair follicle. Cytochrome P-450-aromatase content in women's frontal hair follicles was six times greater than in frontal hair follicles in men. Frontal hair follicles in women had 3 and 3.5 times less 5alpha-reductase type I and II, respectively, than frontal hair follicles in men. These differences in levels of androgen receptor and steroid-converting enzymes may account for the different clinical presentations of androgenetic alopecia in women and men.
Article
In a previous study, we reported a significant and dose-dependent suppression of UV-induced erythema in human skin by a topically applied melatonin preparation. The present double-blind randomized study was designed to examine the influence of the application time point of topical melatonin on this antierythema effect. Defined small areas on the lower back of 20 volunteers were treated with 0.6 mg/cm2 melatonin dissolved in a nanocolloid gel carrier either 15 min before or 1, 30 or 240 min after UV irradiation with twice the individual minimal erythema dose delivered by a Multiport Solar UV Simulator (UVA and UVB). The erythemata induced were evaluated by visual scoring and chromametry 24 h after irradiation. Treatment of the skin with melatonin 15 min before UV irradiation proved to almost completely suppress the development of an UV-induced erythema. In contrast, no significant protective effects of melatonin were observed when it was applied after UV irradiation. Topically applied melatonin has a clear-cut protective effect against UV-induced erythema. Free radical scavenging of UV-generated hydroxyl radicals and interference with the arachidonic acid metabolism are possible mechanisms of the melatonin action.
Article
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.
Article
The hair follicle (HF) is the only mammalian organ that undergoes life-long, cyclic transformations from long stages of growth (anagen), via rapid, apoptosis-driven organ involution (catagen) to a stage of relative "resting" (telogen). The controls that underlie these transformations clearly reside in and/or around the HF itself, and are likely to reflect - essentially autonomous, yet highly manipulable - changes in the local signalling milieu of e.g., hair growth-modulatory growth factors, cytokines, hormones and adhesion molecules. Yet the molecular nature and organization of the "hair cycle clock" (HCC) that drives these cyclic switches in the local signalling milieu remain obscure, and there is not even a fully satisfactory theory of hair cycle control. Since deciphering of the HCC is of paramount clinical importance, and since corresponding working hypotheses are badly needed to guide the design of more incisive experiments that identify the elusive central "oscillator" mechanism behind the HCC, we discuss basic requirements any convincing HCC theory should meet. After arguing that at least four distinct timing devices underlie HF chronobiology ("morphogenesis clock", "cycling inducer", "desynchronizer", and the actual HCC), previously proposed HCC theories are briefly and critically reviewed. In the light of intriguing regulatory similarities between the HCC and the cell cycle machinery, we suggest here that the HCC may be driven by autonomous, cell cycle-coupled secretory activities of the HF mesenchyme, namely by changes in the G0/G1-associated secretion of "papilla morphogens" by dermal papilla fibroblasts. Hopefully, this provocative hypothesis will encourage the proposition of novel, comprehensive HCC theories.
Article
To understand better the mechanisms by which thyroid hormone can exert its effects on the hair follicle, we looked for the expression of members of the thyroid hormone receptor (TR) family in human hair follicles. Immunoreactive TRs were detected in both dermal and epithelial compartments of the human pilosebaceous unit. Using reverse transcriptase-polymerase chain reaction, we established that TRbeta1 was the predominant form of TR expressed in the human hair follicle. In addition, we investigated the effects of 3,3', 5-triiodo-L-thyronine (T3) on the survival of human hair follicles in vitro, to understand the role of this thyroid hormone on hair follicle homeostasis. A physiological level of free T3 significantly enhanced human hair survival in vitro.
Article
Finasteride, an inhibitor of type 2 5alpha-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. The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. 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. 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. 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.
Article
Hormone studies have demonstrated the androgen-dependent character of female androgenetic alopecia, but there have been few controlled studies of therapies for alopecia in women. To compare topical minoxidil 2% and cyproterone acetate in the treatment of female alopecia. Sixty-six women with female-pattern alopecia were randomly assigned for 12 cycles into two groups, 33 received two local applications (2 mL day-1) of topical minoxidil 2% plus combined oral contraceptive and 33 received cyproterone acetate 52 mg day-1 plus ethinyl oestradiol 35 microg for 20 of every 28 days. A mean reduction of 2.4 +/- 6.2 per 0.36 cm2 in hairs of diameter > 40 microm was observed in the cyproterone acetate group (P = 0.05) and a mean increase of 6.5 +/- 9 per 0.36 cm2 in the minoxidil group (P < 0.001). Comparison of the total number of hairs at 12 months and the body mass index (BMI) revealed a borderline positive correlation in the cyproterone acetate group (r = 0.39, P = 0.06) and a negative correlation in the minoxidil group (r = -0.42, P < 0.05). No significant difference was observed in the total number of hairs among cyproterone acetate patients according to the presence or absence of other symptoms of hyperandrogenism, whereas in the minoxidil group, the total number of new hairs was higher in patients with isolated alopecia (Delta = 8.1; P < 0.05). Variations in scalp seborrhoea were significant in both groups, but the result was better (for acne and hirsutism as well) in the cyproterone acetate group than in the minoxidil group (P < 0.001). Minoxidil treatment was more effective in the absence of other signs of hyperandrogenism, hyperseborrhoea, and menstrual cycle modifications when the BMI was low, and when nothing argued in favour of biochemical hyperandrogenism. Cyproterone acetate treatment was more effective when other signs were present and when the BMI was elevated, factors that favoured a diagnosis of biochemical hyperandrogenism.
Article
Frequently encountered in dermatologic practice is the woman who is "losing her hair." Needless to say, the emotional overtones in this situation are great. Some men take the state of their hair seriously. Practically all women do. The feminine attitude toward this is suggested by a traditional punishment that has been dealt women through history. To be shorn and shaven is a particularly severe form of reproach. Berg1 expressed woman's concern about her hair very well. "Woman is herself constantly doing something to her hair. She even carries a little mirror everywhere with her with the principal object of looking at her hair to see that it is all right. Obviously it is a source of anxiety to her." This presentation deals with a transitory hair thinning which after a varying period stops and is usually replaced by new hair growth. The occasional permanent hair loss in older women
Article
Classical Laron syndrome is a recessive disease of primary insulin-like growth factor 1 (IGF-1) deficiency and primary growth hormone insensitivity. Affected children have, among other defects, sparse hair growth and frontal recessions. The hair is thin and easy to pluck. Young adults have various degrees of alopecia, more pronounced in males. The aim of the present study was to investigate the effect of primary IGF-1 deficiency on hair structure. The study sample included 11 patients with Laron syndrome--5 children (2 untreated) and 6 adults (5 untreated). Hairs were examined by light and electron microscopy. The most significant structured defect, pili torti et canaliculi, was found in 2 young, untreated patients. Grooving, tapered hair and trichorrhexis nodosa were found in the remainder. IGF-1-treated patients had either none or significantly fewer pathological changes compared to the untreated patients. This is the first documentation of the role of primary IGF-1 deficiency on hair structure in human beings.
Article
It was recently discovered that mammalian skin can produce serotonin and transform it into melatonin. Pathways for the biosynthesis and biodegradation of serotonin and melatonin have been characterized in human and rodent skin and in their major cellular populations. Moreover, receptors for serotonin and melatonin receptors are expressed in keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. Melatonin exerts receptor-independent effects, including activation of pathways protective of oxidative stress and the modification of cellular metabolism. While serotonin is known to have several roles in skin-e.g., pro-edema, vasodilatory, proinflammatory, and pruritogenic-melatonin has been experimentally implicated in hair growth cycling, pigmentation physiology, and melanoma control. Thus, the widespread expression of a cutaneous seorotoninergic/melatoninergic syste,m(s) indicates considerable selectivity of action to facilitate intra-, auto-, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner. Notably, the cutaneous melatoninergic system is organized to respond to continuous stimulation in contrast to the pineal gland, which (being insulated from the external environment) responds to discontinuous activation by the circadian clock. Overall, the cutaneous serotoninergic/melatoninergic system could counteract or buffer external (environmental) or internal stresses to preserve the biological integrity of the organ and to maintain its homeostasis.-Slominski, A. J., Wortsman, J., Tobin, D. J. The cutaneous serotoninergic/melatoninergic system: securing a place under the sun.
Article
While it is undisputed that estrogens (17β-estradiol, E2) are mainly involved in skin physiology and operate as potent hair growth modulators, our knowledge about the estrogen target cells in skin and exact signaling pathways is still very limited. The current review provides an overview of estrogen effects on hair follicle cycling, cutaneous expression of estrogen receptors, and potential functions of estrogens in hair biology. We discuss potential target genes of estrogen receptor-mediated signaling in the skin, explore the interplay of estrogens with other hormones, growth factors and enzymes, and define major open questions in this intriguing and far too long neglected area of hair research. Östrogene (17β-Östradiol, E2) haben maßgeblichen Einfluß auf die Physiologie der Haut und das Haarwachstum, es mangelt jedoch an grundlegenden Kenntnissen über die genauen Wirkungsmechanismen und Zielzellen, die diesen Einflüssen zugrunde liegen. Die Effekte von Östrogenen auf den Haarfollikelzyklus, die unterschiedlichen Expressionsmuster der Östrogenrezeptoren im Haarfollikel von Mensch und Maus, sowie bekannte und vermutete Funktionen der Östrogene in der Haarbiologie werden in dieser Arbeit vorgestellt. Potentielle Zielgene sowie die Einflüsse der zahlreichen Modulatoren, wie Wachstumsfaktoren, Hormone und Enzyme in der Vermittlung von Östrogen-Effekten auf die Haut und den Haarfollikel werden diskutiert und offene Fragen erörtert, deren Klärung für die Haarforschung von großer Bedeutung wäre.
Article
Human hair follicles, which are distributed in various and specific sites of the body, appear to have an inherited susceptibility for androgen-dependent growth. Beard, axillary, and frontal scalp dermal papilla cells (DPC) were recently shown to possess the characteristics of androgen target cells. These DPC show strong expression of androgen receptors, and the expression of type II 5alpha reductase is restricted to beard and frontal scalp DPC. These findings suggest that DPC mediate the signals of androgen to follicular epithelial cells in a paracrine fashion. We developed an in vitro co-culture system using DPC and keratinocytes (KC) to characterize the mode of androgen action in human hair follicles. Androgen significantly stimulated the proliferation of KC co-cultured with beard DPC, indicating that beard DPC produce androgen-dependent diffusible growth factors. Insulin-like growth factor-I was identified as one of the androgen-dependent paracrine growth factors produced by beard DPC. We also identified the inhibitory role of androgen on the growth of KC co-cultured with DPC from androgenetic alopecia (AGA) when the DPC were transfected with an expression vector encoding the androgen receptor. This growth suppression of KC was mediated by transforming growth factor-beta1 (TGF-beta1) derived from DPC of AGA, suggesting that TGF-beta1 is a paracrine mediator for AGA.
Article
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. To examine whether topically applied melatonin influences anagen and telogen hair rate in women with androgenetic or diffuse hair loss. 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. 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. 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.
Article
Two drugs which are approved for the treatment of androgenetic alopecia in women in Germany were compared with regard to their influence on hair growth. Patients were randomized to group I (n = 52) who used 2% minoxidil solution twice daily for a period of 12 months or to group II (n = 51) who used 0.025% alfatradiol solution once daily for 6 months and were then switched to 2% minoxidil solution for months 7-12. Changes in hair growth parameters were determined using the TrichoScan. Topical treatment with 2% minoxidil solution for 6 months resulted in a significant increase of cumulative hair thickness (p < 0.0001) and absolute hair density (p < or = 0.0025), whereas these parameters of hair growth remained nearly unchanged after 6 months of treatment with alfatradiol solution. Evaluation of the same parameters from month 7 to month 12 demonstrated that 12 months minoxidil treatment resulted in an increasing stabilization (group I). After the alfatradiol-->minoxidil switch in group II a significant increase in cumulative hair thickness (p < 0.0001) and absolute hair density (p < 0.0001) was achieved. Both study medications were well tolerated. Treatment with minoxidil can induce an increase in hair density and hair thickness,whereas treatment with alfatradiol results in deceleration or stabilization of hair loss.
Haarwachstumsstörun-gen bei Hyperprolaktinämie
  • Orfanosce
OrfanosCE, Hertel H (1988) Haarwachstumsstörun-gen bei Hyperprolaktinämie. Z Hautkr 63:23–26
Comparative gene ex-pression profiling of senescent and androgenetic alopecia using microarray analysis
  • P Mirmirani
  • Karnik
Mirmirani P, Karnik P (2010) Comparative gene ex-pression profiling of senescent and androgenetic alopecia using microarray analysis. In: Trüeb RM, Tobin DJ (Hrsg) Aging hair. Springer, Berlin Heidel-berg New York Tokyo (im Druck)