No / BACKGROUND: Androgenetic alopecia, or male pattern baldness, is a common, progressive disorder where large, terminal scalp hairs are gradually replaced by smaller hairs in precise patterns until only tiny vellus hairs remain. This balding can cause a marked reduction in the quality of life. Although these changes are driven by androgens, most molecular mechanisms are unknown, limiting available treatments. The mesenchyme-derived dermal papilla at the base of the mainly epithelial hair follicle controls the type of hair produced and is probably the site through which androgens act on follicle cells by altering the regulatory paracrine factors produced by dermal papilla cells. During changes in hair size the relationship between the hair and dermal papilla size remains constant, with alterations in both dermal papilla volume and cell number. This suggests that alterations within the dermal papilla itself play a key role in altering hair size in response to androgens. Cultured dermal papilla cells offer a useful model system to investigate this as they promote new hair growth in vivo, retain characteristics in vitro which reflect their parent follicle's response to androgens in vivo and secrete mitogenic factors for dermal papilla cells and keratinocytes. OBJECTIVES: To investigate whether cultured dermal papilla cells from balding follicles secrete altered amounts/types of mitogenic factors for dermal papilla cells than those from larger, normal follicles. We also aimed to determine whether rodent cells would recognize mitogenic signals from human cells in vitro and whether factors produced by balding dermal papilla cells could alter the start of a new mouse hair cycle in vivo. METHODS: Dermal papilla cells were cultured from normal, balding and almost clinically normal areas of balding scalps and their ability to produce mitogenic factors compared using both human and rat whisker dermal papilla cells as in vitro targets and mouse hair growth in vivo. RESULTS: Normal scalp cells produced soluble factors which stimulated the growth of both human scalp and rat whisker dermal papilla cells in vitro, demonstrating dose-responsive mitogenic capability across species. Although balding cells stimulated some growth, this was much reduced and they also secreted inhibitory factor(s). Balding cell media also delayed new hair growth when injected into mice. CONCLUSIONS: Human balding dermal papilla cells secrete inhibitory factors which affect the growth of both human and rodent dermal papilla cells and factors which delay the onset of anagen in mice in vivo. These inhibitory factor(s) probably cause the formation of smaller dermal papillae and smaller hairs in male pattern baldness. Identification of such factor(s) could lead to novel therapeutic approaches.

Androgens are the main regulators of human hair growth stimulating larger, terminal hair development e.g. beard and causing scalp balding, androgenetic alopecia. Hair disorders cause psychological distress but are poorly controlled. Androgens probably act by altering regulatory paracrine factors produced by the mesenchyme-derived dermal papilla. This study aimed to investigate paracrine factors involved in androgen-regulated alopecia, particularly hepatocyte growth factor (HGF) family members, by investigating their in vivo status. Balding and non-balding scalp hair follicles and their component tissues were isolated and analysed by molecular biological methods (reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative PCR and DNA microarray analysis), cell culture and immunohistochemistry. Scalp follicles expressed a range of paracrine messenger genes. The dermal papilla, cultured dermal papilla cells and dermal sheath expressed several HGF family genes, while matrix cells only produced the receptor RON suggesting autocrine roles for HGF and MSP, but a paracrine route only for MSP. Comparing balding and non-balding follicles from the same individuals revealed the expected reduction in several keratin and keratin-related protein genes supporting this approach's validity. There were also significant differences in paracrine factors previously implicated in androgen action by in vitro studies. Several factors believed to increase during androgen stimulation of larger, darker follicles, e.g. IGF-I and SCF, were lowered in balding follicles, while putative inhibitory factors, e.g. TGFß-1, were increased. HGF and MSP and their receptors, c-Met and RON, were significantly reduced. These results increase our understanding of androgen action in human hair follicles; this could lead to better treatments for hair disorders.

Androgens are the main regulators of human hair growth stimulating larger, terminal hair development e.g. beard and causing scalp balding, androgenetic alopecia. Hair disorders cause psychological distress but are poorly controlled. Androgens probably act by altering regulatory paracrine factors produced by the mesenchyme-derived dermal papilla. This study aimed to investigate paracrine factors involved in androgen-regulated alopecia, particularly hepatocyte growth factor (HGF) family members, by investigating their in vivo status. Balding and non-balding scalp hair follicles and their component tissues were isolated and analysed by molecular biological methods (reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative PCR and DNA microarray analysis), cell culture and immunohistochemistry. Scalp follicles expressed a range of paracrine messenger genes. The dermal papilla, cultured dermal papilla cells and dermal sheath expressed several HGF family genes, while matrix cells only produced the receptor RON suggesting autocrine roles for HGF and MSP, but a paracrine route only for MSP. Comparing balding and non-balding follicles from the same individuals revealed the expected reduction in several keratin and keratin-related protein genes supporting this approach's validity. There were also significant differences in paracrine factors previously implicated in androgen action by in vitro studies. Several factors believed to increase during androgen stimulation of larger, darker follicles, e.g. IGF-I and SCF, were lowered in balding follicles, while putative inhibitory factors, e.g. TGFß-1, were increased. HGF and MSP and their receptors, c-Met and RON, were significantly reduced. These results increase our understanding of androgen action in human hair follicles; this could lead to better treatments for hair disorders. / Saudi government

Yes / Background: Platelet rich plasma (PRP), processed from autologous peripheral blood, is used to treat androgenetic alopecia (AGA). Objective: To determine the efficacy of PRP for hair growth promotion in AGA patients in a randomized, blinded, placebo controlled, pilot clinical trial (NCT02074943). Methods: The efficacy of an 8 week, 5 session, PRP treatment course was determined by measuring hair density and hair caliber changes in 10 AGA affected patients. For each PRP sample, the concentrations of selected growth factors were determined using a multiplex assay system. The clinical results were then correlated to the growth factor concentrations in PRP. Results: At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited increased mean hair density (+12.76%) over baseline compared to placebo (+0.99%). Mean hair caliber decreased in both treated and placebo regions (-16.22% and -19.46% respectively). Serial analysis of PRP significant variability in concentrations between patients. Overall, there was a positive correlation between GDNF concentration and hair density (p= 0.004). Trends, though not statistically significant, were also observed for FGF2 and VEGF. Limitations: Small sample size and lack of comparative cohorts receiving protocol variations limit confidence in the study data. Conclusions: This small pilot clinical trial suggests PRP treatment may be beneficial for AGA. However, the variable hair growth responses between patients indicate there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in growth factor concentration in PRP suggests standardization of growth factors post-processing might improve hair growth responses. / RepliCel Life Sciences Inc. (Canada)

Yes / Pattern Hair Loss (PHL) is a chronic regressive condition of the scalp, where follicular miniaturisation and decreased scalp hair coverage occurs in affected areas. In all PHL cases there is a measurable progressive shortening of the terminal hair growth duration, along with reduced linear growth rates. In both genders, PHL initially shows an increase in short telogen hairs ≤30mm in length, reflecting a cycle completion of under six months in affected terminal hair follicles. To understand the miniaturisation process, we re-examine the dynamics of miniaturisation and ask the question, 'why do miniaturised hair follicles resist treatment?' In the light of recent developments in relation to hair regeneration, we looked back in the older literature for helpful clues 'lost to time' and reprise a 1978 Hermann Pinkus observation of an array of elastin deposits beneath the dermal papilla following subsequent anagen/telogen transitions in male balding, originally described by Arao and Perkins who concluded that these changes provide a "morphologic marker of the entire biologic process in the balding scalp". Thus, we have reviewed the role of the elastin-like bodies in hair pathology and we propose that alterations in elastin architecture may contribute to the failure of vellus-like hair reverting back to their terminal status and may indicate a new area for therapeutic intervention.

Hair plays an important role in human social and sexual communication. The androgen-stimulated, patterned loss of hair in cases of androgenetic alopecia (or common baldness) in genetically pre-disposed individuals, is associated with ageing and can cause marked phychological distress. However, it is poorly controlled. To investigate the effectiveness of daily topical application of a Chinese medicine-derived herbal mixture, Xiantene, on balding progression, two double-blind, placebo-controlled studies (3 and 12 months) were carried out on balding men using the trichogram approach. Xiantene significantly increased both the total number of hairs and those in anagen, improving the ratio of anagen:telogen hairs. This suggests that topical Xiantene increased the length of the anagen phase and may promote a cessation, or partial reversal, of the progression of androgenetic alopecia in men. Canities, loss of scalp hair colour, is another mark of ageing. To investigate whether early greying may protect follicles from androgenetic alopecia, the extent of alopecia, assessed using the Hamilton scale, was compared between men who first became grey before, or after, 30. Both alopecia and greying increased with age in 843 men (217 European, 626 Thai) whenever they first started greying. However, men who showed greying before 30 were significantly less bald, though more grey, in both groups. Hair follicle melanocytes synthesise the pigment melanin, producing reactive oxygen species (ROS) and oxidative stress; losing melanocyte pigmentary activity, and therefore these toxic factors, appears to enable hair follicles to maintain their full size for longer, despite the androgen drive to miniaturisation.

Abstract A hypothesis is created that an association between androgenetic alopecia (AGA) and serious cardiovascular events, such as myocardial infarction and fatal ischaemic heart disease has been reported, but the mechanism explaining this association has remained unclear. The aim of this study was to analyze the relationship between insulin resistance, (coronary) artery disease and AGA. Moreover, a hypothesis on the role of electromagnetic cell adhesion in the development of AGA is presented. In the present series of men aged 19–50 years (n = 154) with early (<  35 years of age), significant AGA of at least grade 3 (vertex) in the Hamilton classification modified by Norwood (Norwood 1975) was hyperinsulinaemia encountered twice as often as on age-matched controls. Other signs of the insulin resistance syndrome, such as obesity, lipid lowering and antihypertensive drugs were also found to correlate with early AGA. In a population-based case-control study, male patients living a small rural town who had undergone an urgent or elective coronary revascularization procedure (n =  85) and their age-matched controls were analysed after stratification by age at operation and hair status. The findings showed AGA to be more common coronary artery disease and early AGA as those with early coronary artery disease. In a population aged 63 years (n = 541, 217 men), neck circumference was found to correlate with the conventional anthropometric indicators of insulin resistance and with elevated serum insulin in both genders, which means that neck circumference is a simple anthropometric indicator of android type obesity and insulin resistance. In the same female population other factors of insulin resistance (whr, waist circumference, serum insulin level and microalbuminuria) were associated with marked (grade 2 or 3 on a modified Ludwig scale) hair loss. Paternal heredity was clearly characteristic of AGA in both genders, particularly of early AGA in men. We present a hypothesis that the overactive androgen state inhibits cell mitosis in the dermal papilla of the hair follicle and contributes to a weaker electromagnetic attraction between the undifferentiated germ cells and the dermal papilla and also to a shortened anagen phase of the hair growth cycle. Insulin resistance has an additional pathogenic role in the excessive miniaturization of the hair follicle. As a conclusion, along with android obesity, early alopecia can be considered a sign of insulin resistance and a possible risk factor for an early onset of coronary artery disease. Timely intervention in the risk factors may help to slow down or prevent the development of arterial disease and possibly also to alleviate the cosmetic and psychosocial consequences of hair loss. / Tiivistelmä Insuliiniresistenssin, (sepel)valtimotaudin ja AGA:n välillä on yhteyksiä. Taustalla olevat patomekanismit ovat kuitenkin epäselviä. Tässä väitöskirjatyössä tutkittiin insuliiniresistenssin ja (sepel)valtimotaudin suhdetta AGA:an. Lisäksi luotiin hypoteesi sähkömagneettisen soluadheesion roolista AGA:n kehittymisessä. Aineiston 19–50-vuotiailla miehillä (n = 154), joilla oli varhainen (< 35 v), merkittävä, vähintään kolmannen (vertex) asteen AGA Norwoodin modifioiman Hamiltonin luokituksen mukaan (Norwood 1975) seerumin insuliinipitoisuus oli suurentunut liki kaksi kertaa useammin kuin samanikäisillä verrokeilla. Myös muiden insuliiniresistenssioireyhtymään liitettyjen vaaratekijöiden, kuten ylipainon, havaittiin liittyvän varhaiseen AGA:an. Pienen maaseutukaupungin kaikki sepelvaltimoiden revaskularisaatioon joutuneet miehet (n = 85) analysoitiin toimenpiteeseen joutumisiän ja hiusstatuksen mukaan. Tulokset osoittavat AGA:n olevan yhteydessä sepelvaltimotautiin ja varhaisen AGA:n varhaiseen sepelvaltimotautiin. Aineiston 63-vuotiailla (n = 541, miehiä 217) kaulan ympärysmitan todettiin korreloivan selvästi antropometrisiin, insuliiniresistenssiä kuvaaviin mittoihin ja seerumin insuliinipitoisuuden kasvuun sekä miehillä että naisilla. Kaulan ympärysmitta soveltuu siten käytettäväksi antropometrisena mittana androidityyppisen ylipainon ja insuliiniresistenssin selvittämisessä. Saman väestöotoksen naisilla tehdyssä tutkimuksessa havaittiin muiden insuliiniresistenssin osatekijöiden (vyötärö-lantiosuhteen, vyötärön ympärysmitan, seerumin insuliinipitoisuuden ja mikroalbuminurian) liittyvän huomattavaan hiustenlähtöön (asteet II ja III modifioidulla Ludwigin skaalalla). AGA:ssa isän suvun perimän vaikutus oli selvä molemmilla sukupuolilla. Se oli voimakas erityisesti miesten varhaisessa AGA:ssa. Laatimamme hypoteesin mukaan suuri androgeenipitoisuus estää dermaalipapillan solujen mitoosia ja heikentää sähkömagneettista vetovoimaa. Tällöin hiusfollikkelin solujen määrää vähenee ja hiuksen kasvuvaihe lyhenee haittaavasti. Insuliiniresistenssillä on hypoteesin mukaan toissijainen rooli hiusfollikkelin pienenemisprosessissa. Aikaista hiustenlähtöä androidin ylipainon ohella voidaan pitää insuliiniresistenssin merkkinä ja riskinä sepelvaltimotaudin tavanomaista aiempaan ilmaantumiseen. Puuttumalla ajoissa vaaratekijöihin valtimotaudin kehittymistä voidaan hidastaa tai estää ja ehkä myös vähentää kosmeettisesti ja psykososiaalisesti haittaavaa hiusten menetystä.

Hair plays an important role in human social and sexual communication. The androgen-stimulated, patterned loss of hair in cases of androgenetic alopecia (or common baldness) in genetically pre-disposed individuals, is associated with ageing and can cause marked phychological distress. However, it is poorly controlled. To investigate the effectiveness of daily topical application of a Chinese medicine-derived herbal mixture, Xiantene, on balding progression, two double-blind, placebo-controlled studies (3 and 12 months) were carried out on balding men using the trichogram approach. Xiantene significantly increased both the total number of hairs and those in anagen, improving the ratio of anagen:telogen hairs. This suggests that topical Xiantene increased the length of the anagen phase and may promote a cessation, or partial reversal, of the progression of androgenetic alopecia in men. Canities, loss of scalp hair colour, is another mark of ageing. To investigate whether early greying may protect follicles from androgenetic alopecia, the extent of alopecia, assessed using the Hamilton scale, was compared between men who first became grey before, or after, 30. Both alopecia and greying increased with age in 843 men (217 European, 626 Thai) whenever they first started greying. However, men who showed greying before 30 were significantly less bald, though more grey, in both groups. Hair follicle melanocytes synthesise the pigment melanin, producing reactive oxygen species (ROS) and oxidative stress; losing melanocyte pigmentary activity, and therefore these toxic factors, appears to enable hair follicles to maintain their full size for longer, despite the androgen drive to miniaturisation. / Tri-Mill Charitable Trust, Global Beauty International Management Ltd.

Yes / The development of androgenetic alopecia is associated with a risk of developing cardiovascular diseases, but the association of alopecia areata with cardiovascular diseases in humans is largely unexplored. We measured the plasma level of two common cardiovascular disease markers, cardiac troponin I and Creactive protein, in alopecia areata and androgenetic alopecia-affected subjects. Also, we investigated the possible presence of pro-apoptotic factors in the plasma of hair loss subjects. The mean plasma cardiac troponin I level was highest in alopecia areata subjects, moderately higher in androgenetic alopecia subjects, and lowest in subjects without hair loss (p < 0.05). Alopecia areata subjects not receiving treatments had highest levels of cardiac troponin I (p < 0.05). Alopecia areata plasma samples with high cardiac troponin I levels also induced significantly higher rates of cardiomyocyte apoptosis in cell culture assays. The results suggest the potential for increased heart remodelling. Close monitoring of cardiovascular health in alopecia areata subjects, as well as subsets of androgenetic alopecia patients, may be appropriate. / Canadian Institutes of Health Research (CIHR; MOP-82927). EW is the recipient of a Banting Postdoctoral Fellowship (SAC-92845).

Orientador: Helio Amante Miot / Resumo: Introdução: Minoxidil tópico é o único medicamento com aprovação pelo FDA (Food and Drug Administration) para tratamento da alopecia de padrão feminino (APF). Muitas pacientes interrompem o tratamento prematuramente devido a falta de eficácia, intolerância ou por alteração na textura dos fios de cabelo. Minoxidil oral mostrou-se efetivo para tratamento da APF em estudo não controlado. Objetivo: Comparar eficácia, segurança e tolerabilidade do minoxidil 1 mg oral uma vez ao dia versus minoxidil 5% solução tópica uma vez ao dia no tratamento da APF. Métodos: Estudo prospectivo, randomizado, paralelo, comparativo, avaliador cego com duração de 24 semanas conduzido em um único centro de janeiro de 2017 a março de 2018 incluindo 52 mulheres (18-65 anos) com APF. Participantes foram randomizadas para receber minoxidil oral 1 mg ao dia ou minoxidil 5% tópico uma vez ao dia. O desfecho primário foi a variação na densidade de fios na área alvo. Desfechos secundários: variação na densidade de fios terminais na área alvo, escore na avaliação fotográfica panorâmica por avaliadores cegos, variação no escore da escala de queda, variação no escore do Women's Androgenetic Alopecia Quality of Life Questionnaire (WAA-QoL). Resultados: Participantes de ambos os grupos apresentaram melhora na densidade de fios na área alvo (p<0,01), porém, sem diferença entre os grupos (p=0,09): oral 12% (IC95%: 8,0 – 16,1%) e tópico 7,2% (IC95%: 1,5 - 12,9%). Houve melhora na densidade de fios terminais: oral 6... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Topical minoxidil is the only FDA (Food and Drug Administration) approved drug for female pattern hair loss (FPHL). Many patients discontinue treatment prematurely due to lack of efficacy, intolerance or altered hair texture. Oral minoxidil was effective for FPHL in uncontrolled studies. Objectives: To compare the efficacy, safety and tolerability of once-daily treatment with 1 mg oral minoxidil versus once-daily 5% minoxidil solution applied topically for FPHL. Methods: A 24-week, prospective, randomized, open-label, parallel, two-arm comparative, evaluator-blinded study conducted in a single center from January 2017 through March 2018 including 52 women (18-65 years old) with FPHL. Participants were randomly assigned to receive once daily minoxidil 1 mg orally or once a day minoxidil 5% solution applied topically. The primary endpoint was change from baseline in hair density from a target area at week 24. Secondary endpoints were change in terminal hair density, global photographic assessment by three group-blinded evaluators, hair shedding score, and the Women's Androgenetic Alopecia Quality of Life Questionnaire (WAA-QoL). Results: Participants of both groups had improvement of hair density in the target area (p<0.01), without difference between the groups (p=0.09): oral 12% (CI95%: 8.0- 16.1%) and topical 7,2% (CI95%: 1.5-12.9%). There was improvement on terminal hair density: oral 6% (IC95%: 2.9 – 8.6%) and topical 2,7% (IC95%: -1.4 – 6.8%), with no differ... (Complete abstract click electronic access below) / Doutor