No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Androgenetic alopecia
Abstract
Worldwide, androgenetic alopecia is the most common type of non scarring-alopecia. It affects 45% of men and 10% of women of the general population. In this article aetiology, clinical diagnosis, and current treatments of this hair disorder will be reviewed.
ResearchGate has not been able to resolve any citations for this publication.
Background:
In the search for alternative agents to oral finasteride and topical minoxidil for the treatment of androgenetic alopecia (AGA), melatonin, a potent antioxidant and growth modulator, was identified as a promising candidate based on in vitro and in vivo studies.
Materials and methods:
One pharmacodynamic study on topical application of melatonin and four clinical pre-post studies were performed in patients with androgenetic alopecia or general hair loss and evaluated by standardised questionnaires, TrichoScan, 60-second hair count test and hair pull test.
Results:
FIVE CLINICAL STUDIES SHOWED POSITIVE EFFECTS OF A TOPICAL MELATONIN SOLUTION IN THE TREATMENT OF AGA IN MEN AND WOMEN WHILE SHOWING GOOD TOLERABILITY: (1) Pharmacodynamics under once-daily topical application in the evening showed no significant influence on endogenous serum melatonin levels. (2) An observational study involving 30 men and women showed a significant reduction in the degree of severity of alopecia after 30 and 90 days (P < 0.001) based on questionnaires completed by investigators and patients. (3) Using a digital software-supported epiluminescence technique (TrichoScan) in 35 men with AGA, after 3 and 6 months in 54.8% to 58.1% of the patients a significant increase of hair density of 29% and 41%, respectively was measured (M0: 123/cm(2); M3: 159/cm(2); M6: 173/cm(2);) (P < 0,001). (4) In 60 men and women with hair loss, a significant reduction in hair loss was observed in women, while hair loss in men remained constant (P < 0.001). (5) In a large, 3-month, multi-center study with more than 1800 volunteers at 200 centers, the percentage of patients with a 2- to 3-fold positive hair-pull test decreased from 61.6% to 7.8%, while the percentage of patients with a negative hair-pull test increased from 12.2.% to 61.5% (P < 0.001). In addition, a decrease in seborrhea and seborrheic dermatitis of the scalp was observed.
Conclusions:
Since safety and tolerability in all of the studies was good, the topical application of a cosmetic melatonin solution can be considered as a treatment option in androgenetic alopecia.
The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA-development. However a significant fraction of the overall heritable risk still awaits identification. Furthermore, understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the twelve genomic loci that showed suggestive association (5 × 10(-8)<P<10(-5)) with AGA in a recent meta-analysis. We analyzed a replication-set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10(-15)) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A plays a functional role in AGA-etiology. Thus, our study provides genetic evidence supporting an involvement of WNT-signaling in AGA-development.Journal of Investigative Dermatology accepted article preview online, 28 January 2013;. doi:10.1038/jid.2013.43.
Female pattern hair loss (FPHL) or androgenic alopecia is the most common type of hair loss affecting women with reduced hair density and can have a serious psychological impact. It is characterized by progressive replacement of slow cycling terminal hair follicles by miniaturized, rapidly cycling vellus hair follicles. The frontal hair line may or may not be preserved. The aim of this review was to assess the evidence for the effectiveness and safety of the treatments available for FPHL. Searches included: Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Clinical Trials in The Cochrane Library, MEDLINE, EMBASE, AMED, PsycINFO, LILACS and several ongoing trials registries (October 2011). Randomized controlled trials in women with FPHL were identified. Twenty-two trials, comprising 2349 participants, were included. A range of interventions was evaluated, with 10 studies examining varying concentrations of minoxidil. Pooled data from four studies indicated that a greater proportion of participants treated with minoxidil reported a moderate increase in their hair regrowth compared with placebo (relative risk 1·86, 95% confidence interval 1·42-2·43). There was no difference between the number of adverse events experienced in the twice daily minoxidil and the placebo intervention groups, except for a reported increase with minoxidil 5% twice daily. Single studies accounted for most of the other comparisons, which were assessed as either having high risk of bias and/or they did not address the prespecified outcomes for this review and provided limited evidence of either the effectiveness or safety of these interventions. Further well-designed, adequately powered randomized controlled trials investigating other treatment options are still required.
Taurine is a naturally occurring β-amino acid produced by methionine and cysteine metabolism. It is involved in a variety of physiological functions, including immunomodulatory and antifibrotic. Taking advantage of the ability of human hair follicle grown in vitro to recapitulate most of the characteristic features of normal hair follicle in vivo, we studied (i) taurine uptake by isolated human hair follicles; (ii) its effects on hair growth and survival rate; and (iii) its protective potential against transforming growth factor (TGF)-β1, an inhibitor of in vitro hair growth and a master switch of fibrotic program. We showed that taurine was taken up by the connective tissue sheath, proximal outer root sheath and hair bulb, promoted hair survival in vitro and prevented TGF-β1-induced deleterious effects on hair follicle.
La taurine est un β-amino acide naturel qui dérive du métabolisme de la méthionine et de la cystéine. Elle est impliquée dans un grand nombre de fonctions physiologiques, et présente en particulier des activités immuno-modulatrices et antifibrotiques. En s'appuyant sur le modèle du follicule pileux in vitro, qui reproduit de nombreuses caractéristiques du follicule normal in vivo, nous avons étudié (i) l'incorporation et la distribution de la taurine dans un follicule pileux isolé, (ii) son effet sur la croissance et la survie du follicule et (iii) son rôle protecteur vis-à-vis du TGF-β1, à la fois inhibiteur de la croissance du follicule et inducteur du programme fibrotique. Nous montrons que la taurine est captée par la gaine conjonctive, la gaine externe proximale et le bulbe, assure la survie du follicule in vitro et s'oppose à l'effet délétère du TGF-β1 sur le follicule pileux.
Chemotherapy-induced hair loss is one of the most serious and feared adverse effects of cancer therapy. Almost all traditional chemotherapeutic agents induce a more or less severe alopecia. At present, there is no effective treatment capable of preventing this damage. Several different experimental approaches, using various animal models, have been investigated over the last years, with promising results. Sulphur-containing amino acids (cystine, cysteine) are essential components for the health of normal hair. L: -Cystine is used in the treatment of various forms of alopecia. Vitamin B6 plays an important role in the development and maintenance of the skin and it is useful in reducing hair loss. In the present study, we demonstrated that the combined oral administration at high dosages of L: -cystine (1,600 or 800 mg/kg body weight/day) and vitamin B6 (160 or 80 mg/kg body weight/day) is an effective chemopreventive treatment against alopecia induced by doxorubicin treatment (1.1 mg/kg body weight intravenously) in C57BL/6 mice.
Thyroid dysfunction is classically associated with alopecia. Studies focusing on manual thyroid examinations, with ultrasonography of palpable abnormalities, in alopecia patients are lacking.
To examine the clinical utility of manual and sonographic evaluation of the thyroid in alopecia patients.
A retrospective chart review was performed among patients diagnosed with alopecia.
We found that 20.2% (74/367) of manual thyroid exams performed were deemed abnormal and 78.8% (41/52) of patients who had an ultrasound had an abnormal finding. Twenty two of the 74 patients did not obtain the requested ultrasound. Non-scarring alopecia was associated with 36 of 41 patients with abnormal ultrasounds (Telogen effluvium 29.3%, Androgenetic alopecia 27.8%, Alopecia areata 24.4%, and Traction alopecia 9.8%). No one specific structural abnormality was associated with a specific hair loss type. Of note, 78% (32/41) of patients with an abnormal ultrasound exam had normal thyroid function tests and only 9/41 (22%) patients had both.
THESE INCLUDE: a retrospective study design, small sample size, use of multiple sites for laboratory and sonographic thyroid evaluation, and a high attrition rate for ultrasound evaluation.
This study revealed that the manual examination of the thyroid in alopecia patients may identify additional thyroid abnormalities not detected with serologic evaluation alone. Further prospective studies are required to evaluate the necessity and significance of manual thyroid palpation and subsequent ultrasound studies in this patient population.
The role of genetic predisposition and the influence of sex steroid hormones are indisputable to the pathogenesis of male androgenetic alopecia (MAGA). The role of sex steroid hormones in female pattern hair loss (FPHL) is less known. A good knowledge of the pathophysiology underlying MAGA and FPHL empowers the clinician to confidently counsel patients and make informed therapeutic decisions. Vigorous research in recent years has provided greater insight into the role of genetics and sex steroids in physiological hair growth and cycling, as well as in hair follicle miniaturization, the histological hallmark of MAGA and FPHL. In the present review article directed towards clinicians, we discuss the current understanding of the role of androgens and oestrogens, as well as genetic associations with MAGA and FPHL. We also briefly discuss the interpretation of direct-to-consumer genetic testing for baldness to help clinicians understand the limitations of such tests.
Estradiol (E(2)) applied topically twice weekly to mouse skin at doses as low as 1 nmol inhibited hair growth by blocking the transition of the hair follicle from the resting phase (telogen) to the growth phase (anagen). In contrast, application of </=10 nmol of other steroids produced limited inhibition. Topical treatment with the estrogen receptor (ER) antagonist ICI-182780 reversed the effects of E(2), and when applied alone, ICI-182780 caused a telogen-to-anagen transition. Both E(2) and ICI-182780 were highly effective at their site of application but not at distant sites, indicating the direct rather than secondary systemic nature of their effects. Western analysis detected a 65-kDa ER-alpha immunoreactive dermal protein, and Northern analysis revealed the presence of a 6.7-kb ER-alpha mRNA. A ribonuclease protection assay confirmed the presence of ER-alpha transcripts but failed to detect ER-beta transcripts. These findings implicate a skin-specific ER-alpha pathway in the regulation of the hair follicle cycle.
Female pattern hair loss is a frequent and distressing condition.
To evaluate vs. control, the effects on hair loss of a 6-month supplementation with specific omega 3&6 and antioxidants.
One hundred and twenty healthy female subjects participated in this 6-month, randomized, comparative study. The primary endpoint was the change in hair density evaluated on standardized photographs. Secondary endpoints included changes in telogen hair percentage and diameter distribution of anagen hair (>40 µm vs. ≤40 µm) measured by trichogram. Overall changes in hair density and diameter were also measured by trichometer and by subjects' self-assessment.
After 6 months of treatment, photograph assessment demonstrated a superior improvement in the supplemented group (P < 0.001). The telogen hair percentage was significantly (P < 0.001) reduced in the supplemented group. The proportion of nonvellus anagen hair (>40 µm) increased compared to the control group. The trichometer index increased in the supplemented group, while it decreased in the control group. A large majority of supplemented subjects reported a reduction in hair loss (89.9% of subjects at 6 months), as well as an improvement in hair diameter (86.1%) and hair density (87.3%).
A 6-month supplementation with omega 3&6 and antioxidants acts efficiently against hair loss in improving hair density and reducing the telogen percentage and the proportion of miniaturized anagen hair. Objectively measured improvements were confirmed by the subjects' perception of efficacy.
© 2015 Wiley Periodicals, Inc.
Introduction:
Alopecia is a common concern encountered in the medical practice. Treatment approach varies according to the type and severity of alopecia. However, available treatment options have limited efficacy and several adverse effects. Presently, there are different treatment options being studied to overcome these limitations. Additionally, cellular pathways involved in the pathophysiology of alopecia are further being clarified to potentially target pathogenic molecules.
Areas covered:
We searched the literature for recently published articles discussing new treatment options as well as mechanisms involved in alopecia. We discuss the use of stem cells, growth factors, cellular pathways and robotic hair transplant, among other emerging therapies used for alopecia.
Expert opinion:
Future looks very promising and new effective treatments such as janus kinase inhibitors could possibly be available for alopecia areata. The stem-cell technology is advancing and companies involved in hair follicle neogenesis are starting clinical trials on patients with androgenetic alopecia.
Currently, topical minoxidil and finasteride are the only treatments that have been FDA approved for the treatment of female pattern hair loss and androgenetic alopecia. Given the incomplete efficacy and sife effect profile of these medications, some patients utilize alternative treatments to help improve this condition. In this review, we illustrate the scientific evidence underlying the efficacy of these alternative approaches, including biotin, caffeine, melatonin, a marine extract, and zinc.
J Drugs Dermatol. 2014;13(7):809-812.
Acute telogen effluvium (ATE) is often associated with female androgenetic alopecia (FAA), but predictive factors of ATE–FAA association and clinical factors or therapies that may influence the progression of ATE to chronic telogen effluvium (CTE) have not been reported. We have identified predictive factors of ATE–FAA association and retrospectively evaluated the impact of therapies on the progression to CTE. Conclusions are as follows: (i) Triggering cause is a significant independent factor that predicts association of ATE with FAA. (ii) Triggering causes with higher risk of concurrent FAA are severe diet, iron deficiency, and thyroid dysfunction. (iii) Patients suffering ATE may benefit from different therapeutic approaches (depending on which is the triggering cause) to prevent or treat the association with FAA. (iv) Minoxidil use shows a trend to lower the percentage of progression to CTE. (v) Apart from treating the precipitating cause, the different additional oral treatments used have not shown any correlation with progression to CTE.
Importance:
Identifying predictors of mortality from diabetes mellitus (DM) and heart disease can help shape treatment strategies. Presence of androgenetic alopecia (AGA) might be such a predictor.
Objective:
To determine whether the presence of AGA is associated with an elevated rate of mortality from DM and heart disease in both sexes after adjustment for potential confounders.
Design:
A population-based prospective cohort study.
Setting:
Community-based integrated screening in Taiwan.
Participants:
A total of 7252 subjects aged 30 to 95 years participated in the baseline AGA survey using the Norwood and Ludwig classifications between April and June 2005. Baseline information on metabolic syndrome (MetS) and other possible risk factors was also collected. We then followed this cohort over time to ascertain death and cause of death until December 2010. INTERVENTIONS OR EXPOSURES: Application of Norwood and Ludwig ALA classifications to study population.
Main outcomes and measures:
Deaths from DM and heart disease.
Results:
Among the 7126 subjects (2429 men and 4697 women) who provided complete data, there were 70 deaths from DM and heart disease during the 57-month follow-up period. Subjects with moderate to severe AGA vs normal or mild AGA had a significantly higher risk of mortality from DM (adjusted hazard ratio [HR], 2.97; 95% CI, 1.26-7.01) (P = .01) and heart disease (adjusted HR, 2.28; 95% CI, 1.00-5.23) (P = .05) after adjusting for age, family history of DM or heart disease, and MetS.
Conclusions and relevance:
AGA is an independent predictor of mortality from DM and heart disease in both sexes. This finding may have significant implications for the identification of risk factors for DM and heart disease in patients with moderate or severe AGA, regardless of whether MetS is present.
Background:
Androgenetic alopecia (AGA) is a common disorder affecting men and women. Finasteride and minoxidil are well-known, effective treatment methods, but patients who exhibit a poor response to these methods have no additional adequate treatment modalities.
Objective:
To evaluate the efficacy and safety of a low-level light therapy (LLLT) device for the treatment of AGA.
Methods:
This study was designed as a 24-week, randomized, double-blind, sham device-controlled trial. Forty subjects with AGA were enrolled and scheduled to receive treatment with a helmet-type, home-use LLLT device emitting wavelengths of 630, 650, and 660 nm or a sham device for 18 minutes daily. Investigator and subject performed phototrichogram assessment (hair density and thickness) and global assessment of hair regrowth for evaluation.
Results:
After 24 weeks of treatment, the LLLT group showed significantly greater hair density than the sham device group. Mean hair diameter improved statistically significantly more in the LLLT group than in the sham device group. Investigator global assessment showed a significant difference between the two groups, but that of the subject did not. No serious adverse reactions were detected.
Conclusion:
LLLT could be an effective treatment for AGA.
Hair loss or alopecia has been portrayed as a modern malady which is aggravated by stressful conditions. Major cases of alopecia were found among individuals of 40s-50s, nowadays, even among the 20s-30s. This study characterized taurine's potential against alopecia caused by chemical stress agents based on the comparison with other commercially available anti-alopecia agents using Caenorhabditis elegans. The criteria used are their effects on the expression of stress markers and measurements of vital signs: lifespan comparison, progeny number, and mobility. C. elegans showed the typical stress symptoms under treatment with tunicamycin, endoplasmic reticulum stress agent. Hsp-70 protein expression increased, while worm's lifespan and per capita progeny number significantly decreased along with an unusually retarded movement. A positive response was shown when worms were treated with taurine along with astressin-B and finasteride. Between the treatments, finasteride showed better outcomes in terms of stress-reducing effects. Taurine helped worms recover more effectively from adverse influence of stress. In conclusion, there is strong evidence that taurine has a great potential as anti-alopecia effect especially against the one caused by the chemical stress. The present study implies that taurine might strongly work against hair loss when used in combination with other commercially available -anti-alopecia agents.
Background:
Although female pattern hair loss (FPHL) has been considered simply the female counterpart of male pattern hair loss in men, the risk factors may differ.
Objective:
We sought to evaluate factors associated with FPHL and to estimate its prevalence in women.
Method:
In total, 26,226 subjects aged 30 years and older participated in a cross-sectional survey. Ludwig and Norwood classifications were used to assess the degree of hair loss. Information on possible risk factors for FPHL was collected using a questionnaire interview.
Results:
The prevalence of FPHL (Ludwig grade >I) for all ages was 11.8% (95% CI 11.5%-12.2%), increasing with advancing age. After controlling for age and family history, statistically significant associations were noted between FPHL and high fasting glucose (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.28), fewer childbirths (OR 1.24, 95% CI 1.12-1.38), breast-feeding (OR 0.88, 95% CI 0.78-0.98), oral contraceptive use (OR 1.21, 95% CI 1.01-1.45), and ultraviolet exposure more than 16 hours per week (OR 1.12, 95% CI 1.02-1.22).
Limitations:
The validity and reliability of FPHL classification may be not perfect in this survey and may need to be verified. Information on family history may be still subject to recall bias.
Conclusions:
Risk factors for FPHL and male androgenic alopecia may differ.
Hair follicle cells have a high turnover. A caloric deprivation or deficiency of several components, such as proteins, minerals, essential fatty acids, and vitamins, caused by inborn errors or reduced uptake, can lead to structural abnormalities, pigmentation changes, or hair loss, although exact data are often lacking. The diagnosis is established through a careful history, clinical examination of hair loss activity, and hair quality and confirmed through targeted laboratory tests. Examples of genetic hair disorders caused by reduced nutritional components are zinc deficiency in acrodermatitis enteropathica and copper deficiency in Menkes kinky hair syndrome.
Androgenetic alopecia is a common cause of hair loss in both men and women. The exact pathogenesis of androgenetic alopecia is not well understood. As the name implies, the role of androgens and genetic susceptibility predisposes to pattern hair loss due to gradual conversion of terminal hair into vellus hair. Male and female pattern hair loss are clinically distinct entities but histologically indistinguishable. The role of sex hormones in females is less understood. This article discusses current understanding of the etiopathogenesis of hair loss in men, diagnostic tests available, and its medical management.
Female pattern hair loss (FPHL) is the most common cause of alopecia in women. FPHL is characterized histologically with increased numbers of miniaturized, velluslike hair follicles. The goal of treatment of FPHL is to arrest hair loss progression and stimulate hair regrowth. The treatments for FPHL can be divided into androgen-dependent and androgen-independent. There is an important adjuvant role for nutritional supplements, light therapy, and hair transplants. All treatments work best when initiated early. Combinations of treatments tend to be more efficacious.
The effect of different dietary protein levels and DL-methionine (Met) supplementation on hair growth and the resulting pelt quality in mink was studied. Four groups of male mink were fed with four isocaloric diets containing 32% (P32), 24% (P24), 16% (P16) or P24+Met (0.8%) crude protein of dry matter (DM) from September to December. Skin biopsies were taken at the pelting. Histological techniques and computer-assisted light microscopy were used to determine the ratio of activity (ROA) of under hairs and guard hairs respectively. The results showed that when the dietary protein level reduced from 32% to 16%, body length, number and diameter of under hairs and guard hairs of minks declined, and pelt length and pelt weight of minks decreased significantly (p < 0.05). These parameters were similar between P32 and P24 with Met supplementation (p > 0.05). The hair follicle density of the winter coat was not influenced by the dietary protein levels and Met supplementation (p > 0.05). Low-protein diets content led to a reduction of hair follicle developing to next phase. It was documented that 24% crude protein of DM with Met supplementation during growing-furring period was sufficient for minks to express their genetic capacity to develop hair follicles and achieve the prime fur characteristics. Overall this study demonstrated that hair growth and hair properties in pelts are very dependent on the dietary protein and Met supply in the growing-furring period of minks.
This article is part of a Special Issue "Neuroendocrine-Immune Axis in Health and Disease." During pregnancy, it is evolutionarily advantageous for inflammatory immune responses that might lead to fetal rejection to be reduced and anti-inflammatory responses that promote transfer of maternal antibodies to the fetus to be increased. Hormones modulate the immunological shift that occurs during pregnancy. Estrogens, including estradiol and estriol, progesterone, and glucocorticoids increase over the course of pregnancy and affect transcriptional signaling of inflammatory immune responses at the maternal-fetal interface and systemically. During pregnancy, the reduced activity of natural killer cells, inflammatory macrophages, and helper T cell type 1 (Th1) cells and production of inflammatory cytokines, combined with the higher activity of regulatory T cells and production of anti-inflammatory cytokines, affects disease pathogenesis. The severity of diseases caused by inflammatory responses (e.g., multiple sclerosis) is reduced and the severity of diseases that are mitigated by inflammatory responses (e.g., influenza and malaria) is increased during pregnancy. For some infectious diseases, elevated inflammatory responses that are necessary to control and clear a pathogen have a negative consequence on the outcome of pregnancy. The bidirectional interactions between hormones and the immune system contribute to both the outcome of pregnancy and female susceptibility to disease.
Dermatoscopy is a noninvasive diagnostic tool that allows the recognition of morphologic structures not visible by the naked eye. Trichoscopy (scalp dermatoscopy and videodermatoscopy) is useful for the diagnosis and follow-up of hair and scalp disorders. However, it is not widely used in the management of hair disorders. This review provides updated information from the literature and our experience on the dermoscopic features of the most common hair and scalp disorders. This will enable dermatologists to make fast diagnoses of tinea capitis and alopecia areata, distinguish early androgenetic alopecia from telogen effluvium, and differentiate scarring from nonscarring alopecia.
Numerous studies have shown an association between polymorphisms in the androgen receptor gene (AR) and the risk for androgenetic alopecia (AGA), but the overall results are still controversial.
To determine, by conducting a meta-analysis, whether the common AR gene polymorphisms confer susceptibility to AGA.
Publications addressing the association between AR gene polymorphisms and risk for AGA were selected from the PubMed, EMBASE and CBMdisc databases. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed using the software programs RevMan (version 5.0.25) and STATA (version 9.2). From these data, odds ratio (OR) with 95% confidence interval (CI) was calculated.
Only eight studies were found, reporting a total of 2074 patients with AGA and 1115 healthy controls. Three common polymorphisms of the AR gene were addressed: a StuI restriction-site polymorphism (rs6152, G>A), and CAG and GGC triplet-repeat polymorphisms. Meta-analysis results identified a significant association between the G allele of the AR StuI polymorphism and the risk for AGA (OR = 2.68, 95% CI 1.71-4.19, P < 0.01), especially in white populations (OR = 2.76, 95% CI 1.71-4.45, P < 0.01). No association was found between the CAG or GGC polymorphism and the risk for AGA (OR = 0.81, 95% CI 0.49-1.34, P = 0.41; OR = 1.01, 95% CI 0.47-2.14, P = 0.99, respectively).
Our meta-analysis suggests that the G allele of AR StuI polymorphism might be a potential risk factor for AGA, especially in white populations. However, we did not find any obvious association of the CAG and GGC triplet-repeat polymorphisms of the AR gene with risk for AGA.
Finasteride 1 mg is indicated for the treatment of men with androgenetic alopecia (AGA). However, more than 5 years efficacy and safety has not been previously reported. To assess the efficacy over 10 years in different age groups of men with AGA. 118 men, between 20 and 61 years, with AGA receiving finasteride (1 mg/day), were enrolled in this uncontrolled study. Efficacy evaluation was assessed with standardized global photographs at T0,T1,T2,T5,T10. Statistical analysis was made using frequency tables and evaluating the chi-square index with its p-value. Better improvements are observed in patients older than 30 years (42.8% aged between 20 and 30 years did not improve also after 10 years) or with higher AGA grades (58.9% for AGA grade IV and 45.4% for AGA grade V had the first improvement just after 1 year). In 21% of cases, the treatment continuation beyond 5 years provided better results. Side effects were referred by 6% of the patients; nevertheless, some of them went on with treatment because of the great results. In our opinion, the result after the first year can help in predicting the effectiveness of the treatment. Its efficacy was not reduced as time goes on; in fact, a big proportion of subjects unchanged after 1 year, improved later on, maintaining a positive trend.
Androgenetic alopecia (AGA) and benign prostatic hyperplasia are both androgen-dependent entities that respond to the blocking of 5-alpha-reductase.
The objective of this study was to determine whether prostatic volumes and urinary flow changes were higher in patients with early-onset AGA than in healthy control subjects.
This was an observational case-control study of 87 men: 45 with early-onset AGA diagnosed in the dermatology department and 42 control subjects. End-point variables were prostatic volume, measured by transrectal ultrasound, and urinary flow, measured by urinary flowmetry. A hormone study was performed on all participants, and the International Prostate Symptom Score and International Index of Erectile Function score were determined.
The groups did not significantly differ in mean age (cases, 52.7 years vs control subjects, 49.8 years; P = .12). Patients with AGA had significantly higher mean prostate volume (29.65 vs 20.24 mL, P < .0001), International Prostate Symptom Score (4.93 vs 1.23, P < .0001), and prostate-specific antigen value (1.53 vs 0.94 ng/mL, P < .0001) and significantly lower maximum urinary flow (14.5 vs 22.45 mL/s, P < .0001) versus control subjects. Binary logistic regression analysis showed a strong association between the presence of AGA and benign prostatic hyperplasia after adjusting for age, urinary volume, urination time, International Prostate Symptom Score, abdominal obesity, glucose levels, systolic blood pressure, insulin levels, fibrinogen, and C-reactive protein (odds ratio = 5.14, 95% confidence interval 1.23-47.36, P = .041).
The study of larger sample sizes would facilitate stratified analyses according to the Ebling type of androgenetic alopecia.
There is a relationship between the presence of AGA and prostate growth-associated urinary symptoms, likely attributable to their pathophysiological similarity. This study suggests that early-onset AGA may be an early marker of urinary/prostatic symptomatology. Future studies may clarify whether treatment of patients with AGA may benefit the concomitant benign prostatic hypertrophy, which would be present at an earlier stage in its natural evolution.
Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects.
We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia.
A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics.
After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS.
Because of differences in the formulations tested, study participants were not blinded to treatment.
Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages.
Unlabelled:
A 47-year-old man who had been using finasteride for male pattern alopecia for 4 years complained of progressive bilateral blurring of vision. His general health had been good, and he was not on any other long-term medication. Examination showed bilateral anterior subcapsular cataracts. Phacoemulsification and insertion of intraocular lenses were performed, and both eyes showed features of intraoperative floppy-iris syndrome (IFIS), including undulation and billowing of the iris, iris prolapse, and pupil constriction. We believe the use of finasteride can be associated with cataract formation and IFIS. Ophthalmologists and physicians prescribing finasteride should be aware of this possible association.
Financial disclosure:
Neither author has a financial or proprietary interest in any material or method mentioned.
Low circulating levels of sex hormone-binding globulin (SHBG) are a strong predictor of the risk of type 2 diabetes. Androgenetic alopecia (AGA) has been related to an increase in cardiovascular risk, but the mechanism of this association has not been elucidated. AGA can be associated with low levels of SHBG and insulin resistance, which could be related to hyperglycemia and type 2 diabetes.
The objective of this study was to evaluate SHBG and blood glucose levels in men and women with early-onset AGA and control subjects to determine whether low levels of SHBG are associated with hyperglycemia.
This case-control study included 240 patients consecutively admitted to the outpatient clinic (Dermatology Department of San Cecilio University Hospital, Granada, Spain), 120 with early-onset AGA (60 men and 60 women) and 120 control subjects (60 men and 60 women) with skin diseases other than alopecia.
Of patients with AGA, 39.1% presented with hyperglycemia (>110 mg/dL) versus 12.5% of controls (P < 0.0001). AGA patients with hyperglycemia or diabetes presented lower significant levels of SHBG than alopecic patients without hyperglycemia or type 2 diabetes, respectively. Patients with AGA and hyperglycemia presented significantly lower levels of SHBG than controls with hyperglycemia (22.3 vs 39.4 nmol/L for AGA patients and controls, respectively, P = .004). No significant differences in SHBG levels were noticed between patients and controls without hyperglycemia. Binary logistic regression showed a strong association between lower SHBG levels and glucose levels greater than 110 mg/dL in patients with AGA even after additional adjustment for sex, abdominal obesity, and free testosterone (odds ratio = 3.35; 95% confidence interval = 1.9-5.7; P < .001).
The study of a wider sample of AGA patients would confirm these findings and would permit analysis of the pathogenic mechanisms underlying the increase in cardiovascular risk in patients with AGA.
An association between early-onset AGA, hyperglycemia/diabetes, and low levels of SHBG was observed in the current study. Low levels of SHBG could be a marker of insulin resistance and hyperglycemia/diabetes in patients with AGA.
When studies of postmenopausal women with hair loss failed to reveal a response to the 5 alpha reductase inhibitor, finasteride, researchers began to question the existence of androgenetic alopecia in women and renamed the clinical entity female pattern hair loss. However, recently published reports of finasteride response in some women with hair loss suggest that an androgenic mechanism is mediating response in this group. Variant repeat nucleotide sequences in exon 1 of the androgen receptor (AR) gene have been shown to determine androgen sensitivity in a variety of androgenic conditions in men and women. In an effort to identify whether this AR variant may help determine which women are likely to respond to finasteride therapy, a pilot study was undertaken. In our 6-month pilot of 13 patients, women with greater androgen sensitivity (<24 cytosine, adenine, and guanine (CAG) repeats) were likely to have a significant response to finasteride 1 mg/day compared with patients treated with placebo, and compared with patients with normal androgen sensitivity (≥24 CAG repeats) based on epigenetic weighted evaluation of the CAG alleles. Results of the present pilot study support the hypothesis that AR-CAG repeats, in conjunction with epigenetic factors, can help determine which women with hair loss will respond to finasteride therapy.
Epidemiological studies have shown that diseases associated with insulin resistance and coronary artery disease are more frequently observed in men with androgenetic alopecia (AGA). We aimed to identify the presence of insulin resistance and metabolic syndrome in male patients with early-onset AGA. Fifty male patients (18-30 years) with AGA stage ≥ 3 (Hamilton-Norwood scale), body mass index < 27 and 40 weight- and age-matched male subjects were the study population. The weight, height, and waist circumference of all patients was measured. Levels of fasting glucose, insulin, and lipids were evaluated and oral glucose tolerance tests undertaken. Insulin resistance was analyzed through various indices and the presence of metabolic syndrome was assessed. Values of diastolic blood pressure and total cholesterol were significantly higher in the AGA group. Among insulin indices, only HOMA insulin resistance (HOMA-IR) and fasting insulin resistance index (FIRI) were higher in the AGA group. Given the criteria for metabolic syndrome, no significant differences were observed between the two groups. Although not supported by the other indices, high scores of HOMA-IR and FIRI suggest that male patients with early onset-AGA have insulin resistance. These data may raise awareness in susceptible individuals that lifestyle changes in the early period of life can reduce the risk of insulin resistance.
Please cite this paper as: Evidence for two independent functional variants for androgenetic alopecia around the androgen receptor gene. Experimental Dermatology 2010; 19: 1026–1028.
Abstract: The gene encoding the androgen receptor (AR) is associated with male pattern baldness (androgenetic alopecia – AGA). In case–control and family analyses, we mapped AR and the adjacent intergenic regions. We found evidence for association with two independent loci, one upstream and previously described and the other downstream and apparently novel. The haplotype comprising these SNPs was strongly associated with AGA (P = 3.75 × 10−5) in 1195 men. We also replicated association with a recently reported non-coding region on chromosome 20 and found that its association with AGA was less strong and independent of that of AR. Our results will help focus future efforts to further define AGA genetic risk.
In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen-potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2-P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT-induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding.
Androgenetic alopecia is the most common form of alopecia in men.
To determine the efficacy and safety of finasteride therapy for patients with androgenetic alopecia.
MEDLINE, EMBASE, CINAHL, Cochrane Registers, and LILACS were searched for randomized controlled trials reported in any language that evaluated the efficacy and safety of finasteride therapy in comparison to treatment with placebo in adults with androgenetic alopecia.
Two reviewers independently evaluated eligibility and collected the data, including assessment of methodological quality (Jadad score). Outcome measures included patient self-assessment, hair count, investigator clinical assessment, global photographic assessment, and adverse effects at short term (≤12 months) and long term (≥24 months). Heterogeneity was explored by testing a priori hypotheses.
Twelve studies fulfilled the eligibility criteria (3927 male patients), 10 of which demonstrated a Jadad score of 3 or more. The proportion of patients reporting an improvement in scalp hair was greater with finasteride therapy than with placebo treatment in the short term (relative risk [RR], 1.81 [95% confidence interval (CI), 1.42-2.32]; I², 64%) and in the long term (RR, 1.71 [95% CI, 1.15-2.53]; I², 16%); both results were considered to have moderate-quality evidence. The number needed to treat for 1 patient to perceive himself as improved was 5.6 (95% CI, 4.6-7.0) in the short term and 3.4 (95% CI, 2.6-5.1) in the long term. Moderate-quality evidence suggested that finasteride therapy increased the mean hair count from baseline in comparison to placebo treatment, expressed as a percentage of the initial count in each individual, at short term (mean difference [MD], 9.42% [95% CI, 7.95%-10.90%]; I², 50%) and at long term (MD, 24.3% [95% CI, 17.92%-30.60%]; I², 0%). Also, the proportion of patients reported as improved by investigator assessment was greater in the short term (RR, 1.80 [95% CI, 1.43-2.26]; number needed to treat, 3.7 [95% CI, 3.2-4.3]; I², 82%) (moderate-quality evidence). Moderate-quality evidence suggested an increase in erectile dysfunction (RR, 2.22 [95% CI, 1.03-4.78]; I², 1%; number needed to harm, 82.1 [95% CI, 56-231]) and a possible increase in the risk of any sexual disturbances (RR, 1.39 [95% CI, 0.99-1.95]; I², 0%). The risk of discontinuing treatment because of sexual adverse effects was similar to that of placebo (RR, 0.88 [95% CI, 0.51-1.49]; I², 5%) (moderate-quality evidence).
Moderate-quality evidence suggests that daily use of oral finasteride increases hair count and improves patient and investigator assessment of hair appearance, while increasing the risk of sexual dysfunction.
To review the key nutritional factors associated with hair loss in long-term parenteral nutrition patients.
The phenomenon of unexplained hair loss is multifactorial, and nonstandard definitions are applied. Deficiencies of essential fatty acids resulting in alopecia and other symptoms appear to have been eliminated by regular use of lipid-containing parenteral nutrition. Zinc is the most frequently suspected deficiency with rapid clinical responses reported from zinc therapy. Alopecia in some infants on parenteral nutrition has been relieved in a few weeks by selenium supplementation as selenite. There may be a relationship between iron depletion and diffuse hair loss in home parenteral nutrition patients at higher risk of anaemia. A serum ferritin level of 70 μg/l should be targeted when hair loss is unexplained. However, there is limited data correlating cessation of hair loss with iron therapy and insufficient evidence to recommend iron supplementation in patients without anaemia. Parenteral nutrition-associated biotin deficiency has not been reported since the vitamin has been routinely added to parenteral nutrition. However, marginal biotin status, associated with diffuse hair loss, could still be prevalent.
Micronutrient status is infrequently monitored and current recommendations for supplementation are nonspecific for hair loss in long-term parenteral nutrition. Studies are required to determine the incidence of marginal zinc, selenium, iron or biotin deficiencies that could manifest as hair loss.
Numerous studies in recent decades have associated male androgenetic alopecia (AGA) with the risk of cardiovascular disease. However, only 3 studies have addressed this association in female patients. Most studies considered the risk of myocardial infarction or mortality as a result of heart disease, without analyzing cardiovascular risk factors.
The objectives of this study were to analyze the presence of cardiovascular risk factors included in the Adult Treatment Panel-III criteria for metabolic syndrome, the prevalence of carotid atheromatosis, hormonal (aldosterone, insulin, testosterone, and sex hormone-binding globulin) factors, and acute phase reactant (C-reactive protein, fibrinogen, D-dimers, erythrocyte sedimentation rate) variables in male and female patients with AGA and in a control group, and to analyze differences among the groups.
This case-control study included 154 participants, 77 with early-onset AGA (40 male and 37 female) and 77 healthy control subjects (40 male and 37 female) from the dermatology department at a university hospital in Granada, Spain.
Metabolic syndrome was diagnosed in 60% of male patients with AGA (odds ratio [OR] = 10.5, 95% confidence interval [CI] 3.3-32.5), 48.6% of female patients with AGA (OR = 10.73, 95% CI 2.7-41.2), 12.5% of male control subjects, and 8.1% of female control subjects (P < .0001). Atheromatous plaques were observed in 32.5% of male patients with AGA (OR = 5.93, 95% CI 1.5-22.9) versus 7.5% of male control subjects (P = .005) and 27% of female patients with AGA (OR = 4.19, 95% CI 1.05-16.7) versus 8.1% of female control subjects (P = .032). Aldosterone and insulin levels were significantly higher in the male and female patients with AGA versus their respective control subjects. Mean values of fibrinogen were significantly higher in male patients with AGA, whereas values of fibrogen, C-reactive protein, and D-dimers were significantly higher in female patients with AGA versus their respective control subjects.
The study of a wider sample of patients with AGA would confirm these findings and allow a detailed analysis of the above factors as a function of the degree of alopecia or between menopausal and premenopausal women.
The determination of metabolic syndrome and ultrasound study of the carotid arteries may be useful screening methods to detect risk of developing cardiovascular disease in male and female patients with early-onset AGA and signal a potential opportunity for early preventive treatment.
Various treatments have been attempted for female pattern hair loss (FPHL), including topical minoxidil, oral antiandrogen and finasteride. But, there is no consensus on the standard treatment options. Clinical efficacy of finasteride in treating FPHL is still in controversy, but there is a tendency to high dose finasteride, which is more effective than lower dose.
The purpose of this study was to evaluate the clinical efficacy of high dose (5 mg/day) oral finasteride in normoandrogenic Asian women with FPHL.
Total of 87 normoandrogenic, pre and post-menopausal women with FPHL were enrolled in this study. They were treated with oral finasteride (Proscar(®)), 5 mg daily for 12 months. Efficacy was evaluated with hair density and thickness changes assessed by phototrichogram and global photographs using 7-point scale.
Eighty-six patients completed 12 months of finasteride treatment schedule. One patient (1.1%) withdrew due to headache. At initial visits, mean hair density was 90 ± 22/cm(2) and mean hair thickness was 64 ± 11 μm. After 12 months of finasteride treatment, hair density was significantly increased to 107 ± 23/cm(2) (P<0.001), and hair thickness was also significantly increased to 70 ± 9 μm (P=0.02). In global photographs, 70 (81.4%) of the 86 patients were improved (57 were slightly, 10 were moderately and four were greatly improved). Patients without any changes were 13 (15.1%) and 3 (3.5%) patients reported slightly aggravated. Four patients (4.6%) reported adverse events (headache, menstrual irregularity, dizziness and increased body hair growth). However, these adverse events were mild and disappeared soon.
Oral finasteride, 5 mg/day, may be an effective and safe treatment for normoandrogenic women with FPHL.
There are racial differences in the prevalence and types of androgenetic alopecia (AGA). The prevalence of AGA has been studied in Caucasians and in some Asian people. In China, although there have been some epidemiological studies carried out in single cities or regions, no multicentre population-based study has been reported.
To study the prevalence and types of AGA in China and to compare the results with those previously reported in Caucasians and in other Asian people.
A community-based study was carried out in six cities of China. Subjects were interviewed face-to-face and completed questionnaires. The degree of AGA was classified according to the Norwood and Ludwig classifications.
In total 17 886 subjects were interviewed and 15 257 completed the questionnaires. In men, the overall prevalence of AGA was 21.3%, with 2.8% in men aged 18-29 years, 13.3% in those aged 30-39 years, 21.4% in those aged 40-49 years, 31.9% in those aged 50-59 years, 36.2% in those aged 60-69 years and 41.4% in those aged 70 years and over. The most common type was frontal and vertex hair loss. A small number of subjects (3.7%) showed 'female pattern' hair loss. In women, the prevalence of AGA was 6.0%, with 1.3% in women aged 18-29 years, 2.3% in those aged 30-39 years, 5.4% in those aged 40-49 years, 7.5% in those aged 50-59 years, 10.3% in those aged 60-69 years and 11.8% in those aged 70 years and over. Ludwig grade I was the most common type. The prevalence of AGA varied between cities. A positive family history was present in 29.7% of men and 19.2% of women with AGA.
The prevalence of AGA in Chinese men and women was lower than in Caucasians and similar to that in Koreans.
Female pattern hair loss (FPHL) is a common trait in which androgens and oestrogens may have a pathogenic role. The aromatase enzyme converts androgens to oestrogens in scalp hair follicles and is differentially expressed in balding and nonbalding scalps of women. Sequence variation in the gene encoding aromatase, CYP19A1, might influence the risk of developing FPHL.
To examine the role of CYP19A1 genetic variation in the heritability of FPHL.
We investigated associations between FPHL and 61 tag single nucleotide polymorphisms (SNPs) representing variation in and around CYP19A1 in 484 caucasian women with grades 3-5 FPHL on the Sinclair scale, and 471 caucasian women with no evidence of hair loss.
For the tag SNP rs4646 (overall genotype frequencies: CC, 53.6%; AC, 39.3%; AA, 7.1%), the genotype CC was more frequent in women with FPHL (58.1%) than controls (48.9%) (P = 0.006). Although this result did not achieve experiment-wide significance (P < 0.001 by permutation testing), subanalyses according to sources of recruitment and ages at presentation revealed consistent patterns of association. In particular, young cases (< 40 years) had the highest frequency of the CC genotype (68.2%) among all subgroups.
These findings suggest that the common rs4646 C allele, which has been associated previously with higher circulating oestrogen levels, might be associated with predisposition to FPHL.
The hair follicle is a cyclic, self renewing epidermal structure which is thought to be controlled by signals from the dermal papilla, a specialized cluster of mesenchymal cells within the dermis. Topical treatments with 17-beta-estradiol to the clipped dorsal skin of mice arrested hair follicles in telogen and produced a profound and prolonged inhibition of hair growth while treatment with the biologically inactive stereoisomer, 17-alpha-estradiol, did not inhibit hair growth. Topical treatments with ICI 182,780, a pure estrogen receptor antagonist, caused the hair follicles to exit telogen and enter anagen, thereby initiating hair growth. Immunohistochemical staining for the estrogen receptor in skin revealed intense and specific staining of the nuclei of the cells of the dermal papilla. The expression of the estrogen receptor in the dermal papilla was hair cycle-dependent with the highest levels of expression associated with the telogen follicle. 17-beta-Estradiol-treated epidermis demonstrated a similar number of 5-bromo-2'-deoxyuridine (BrdUrd) S-phase cells as the control epidermis above telogen follicles; however, the number of BrdUrd S-phase basal cells in the control epidermis varied according to the phase of the cycle of the underlying hair follicles and ranged from 2.6% above telogen follicles to 7.0% above early anagen follicles. These findings indicate an estrogen receptor pathway within the dermal papilla regulates the telogen-anagen follicle transition and suggest that diffusible factors associated with the anagen follicle influence cell proliferation in the epidermis.
Androgenetic alopecia (AGA) is the most common form of alopecia, affecting up to 80% of men and 50% of women in the course of their life. AGA is caused by a progressive reduction in the diameter, length and pigmentation of the hair. Hair thinning results from the effects of the testosterone metabolite dehydrotestosterone (DHT) on androgen-sensitive hair follicles. In women, AGA produces diffuse thinning of the crown region with maintenance of the frontal hairline (Ludwig pattern AGA). In premenopausal women, AGA can be a sign of hyperandrogenism, together with hirsutism and acnes. Male pattern is characterized by bitemporal recession of the frontal hairline, followed by diffuse thinning at the vertex. Today, scalp dermoscopy is used routinely in patients with androgenetic alopecia, as it facilitates the diagnosis and differential diagnosis with other diseases, allows staging of severity, and allows you to monitor the progress of the disease in time and response to treatment. AGA is a progressive disease that tends to worsen with time. Medical treatment of AGA includes topical minoxidil, antiandrogen agents, 5-alpha reductase inhibitors.
Alopecia areata (AA) is a complex, multi-factorial disease where genes and the environment may affect susceptibility and severity. Diet is an environmental factor with the potential to influence disease susceptibility. We considered dietary soy (soya) oil content and the soy-derived phytoestrogen genistein as potential modifying agents for C3H/HeJ mouse AA. Normal haired C3H/HeJ mice were grafted with skin from spontaneous AA affected mice, a method previously shown to induce AA. Grafted mice were given one of three diets containing 1%, 5% or 20% soy oil and observed for AA development. In a separate study, mice on a 1% soy oil diet were injected with 1 mg of genistein three times per week for 10 weeks or received the vehicle as a control. Of mice on 1%, 5%, and 20% soy oil diets, 43 of 50 mice (86%), 11 of 28 mice (39%), and 2 of 11 mice (18%) developed AA, respectively. Four of 10 mice injected with genistein and 9 of 10 controls developed AA. Mice with AA had hair follicle inflammation consistent with observations for spontaneous mouse AA, but no significant association was observed between the extent of hair loss and diet or genistein injection. Mice that failed to develop AA typically experience white hair regrowth from their skin grafts associated with a moderate macrophage and dendritic cell infiltration. Soy oil and derivatives have previously been reported to modify inflammatory conditions. Hypothetically, soy oil compounds may act on C3H/HeJ mice through modulating estrogen-dependent mechanisms and/or inflammatory activity to modify AA susceptibility.
To investigate the effect of cell growth-stimulating agents on human epidermal keratinocytes, we exposed monolayers of normal human keratinocytes derived from foreskin to different concentrations of the amino acid L-cystine, the member of the vitamin B family D-pantothenat, the phytosterol miliacin, and a combination thereof in keratinocyte growth medium. As a test system for the metabolic capacity, we used the activity of mitochondrial deyhdrogenases as measured by XTT, and for the cell proliferation, we determined the BrdU-uptake. The additives, active ingredients of the hair growth drug PRIORIN, were added in the presence of fully supplemented keratinocyte growth medium or a deficient medium without L-cystine, L-methionine, L-histidin, D-pantothenat, epidermal growth factor, and bovine pituary gland extract. Deficient medium itself reduced the metabolic capacity of keratinocytes to 35% compared with keratinocytes in fully supplemented growth medium. In deficient medium cell, proliferation was not measurable. Increasing doses of L-cystine restored the reduced metabolic capacity from 46% (0.009 mg/L) to 54% (0.09 mg/L) and 92% (0.45 mg/L) in deficient medium. Addition of D-pantothenat (0.43 mg/L) enhanced the metabolic capacity to 150% only in fully supplemented growth medium, compared with untreated controls with growth medium. Miliacin (6 mg/mL) increased not only the metabolic capacity (162%) but also stimulated cell proliferation (215%) as measured by BrdU-uptake in growth medium. The combination of all three additives increased the metabolic capacity (245%) synergistically in growth medium. We were able to show effects of D-panthenol, L-lysine, and miliacin on proliferation and metabolic capacity of keratinocyte monocell culture, which was further increased by combination of the three substances. These basic results suggest a beneficial effect on keratinocyte growth and stimulation by products combining these substances (e.g., Priorin). Furthermore, this work emphasizes the suitability of keratinocyte monolayers for pharmacological testings.