Dermal papilla cells (DPCs) play critical roles in hair follicle development, but the underlying mechanisms that contribute to hair regeneration have yet to be fully elucidated, particularly in terms of alterations in androgenetic alopecia patients. In this study, we demonstrated that hypoxia-inducible factor-1α (HIF-1α) is suppressed in scalp tissues of androgenetic alopecia patients and potentially associated with hair follicle development. Using RT-qPCR and western blot, we found that mRNA and protein levels of trichogenic genes, LEF1 and versican (VCAN), were attenuated in HIF-1α knockdown DPCs. Under an in vivo mimicked environment in a three-dimensional spheroid culture, HIF-1α-suppressed DPCs downregulated the expression of hair induction-related genes. Finally, treatment with a HIF-1α activator resulted in the elevated expression of trichogenic genes in DPCs. This study highlights the importance of dermal HIF-1α expression in regulating trichogenic genes and provides a promising therapeutic target and a fundamental tissue engineering approach for hair loss treatment.

[This corrects the article DOI: 10.3389/fmed.2022.1009578.].

Background Men with early-onset androgenetic alopecia (AGA) often have an abnormal hormonal milieu. Objective To ascertain the clinico-phenotypic characteristics and the prevalence of hormonal and metabolic changes in men with early-onset AGA. Methods Consecutive male patients less than 30 years of age with a Norwood-Hamilton grade ≥3 AGA were recruited in this comparative cross-sectional study. After endocrine evaluation they were classified into two groups, that is, Group A consisting of subjects with an altered hormonal profile and Group B with normal hormonal profiles. The groups were assessed for differences in disease phenotype and severity (Norwood-Hamilton grade), insulin resistance and parameters of metabolic syndrome (ATP III guidelines). Results Altered hormonal profiles were seen in 34 of the 100 subjects with AGA, while insulin resistance and metabolic syndrome were noted in 44 and 26 respectively. Altered hormonal profiles were significantly associated with insulin resistance and severe alopecia (grade 4 and above Hamilton-Norwood Scale). Insulin resistant Group A patients had a significantly higher prevalence of severe alopecia (>grade 4) (P = 0.0036). The prevalence of metabolic syndrome was similar in both groups. Limitation The cross sectional study design was a drawback of this study. Further, a control arm without AGA was not included and the sample size of 100 was selected arbitrarily. Conclusion An altered hormonal profile and insulin resistance was noted in a third of the males with early-onset AGA. Subjects with altered hormonal profiles had a higher prevalence of insulin resistance and were likely to have severe grades of AGA.

Pediatric androgenetic alopecia is an underrecognized disorder. A clinical evaluation with trichoscopy should be made in children and adolescents with hair loss and/or reduced hair density. Diagnosis is usually clinical, by observation of the hair loss pattern and performance of trichoscopy. In some cases, hyperandrogenism should be excluded. Although there is no approved therapy for androgenetic alopecia in pediatric age, topical minoxidil, oral minoxidil and topical finasteride may be very useful. Hair transplant may be an option for girls in selected cases. This article is a review of the current state of evidence concerning pediatric androgenetic alopecia.

Genetics is responsible for 80% of androgenetic alopecia (AGA) predisposition. Several single nucleotide polymorphisms (SNPs) have been linked to AGA risk and the metabolism of its first-line therapies. Genotypic and allelic frequencies have not been described in Mexican individuals; therefore, the aim of this study was to describe the genetic distribution of SNPs associated with AGA predisposition and drug metabolism. Using Real Time-PCR, we genotyped SNPs rs4827528 (AR), rs7680591 (FGF5), rs1042028, rs1042157, rs788068 and rs6839 (SULT1A1) and rs776746 (CYP3A5) in 125 (controls = 60, cases = 65) male volunteers from Northern and Western Mexico. The SULT1A1 SNPs rs1042028 (C/T) and rs788068 (T/A/C) resulted in a 100% distribution of the ancestral allele C and mutated allele A, respectively; rs1042028 diverges from the previously reported frequency, while the rs788068 ancestral allele was found to be more predominant than the reported frequency. Rs1042028, rs788068 and rs4827528, were not in Hardy-Weinberg (HW) equilibrium; conversely, rs1042157 and rs6839, rs776746, and rs7680591 followed HW principles. A statistically significant difference (P<0.05) was obtained for the rs1042157 allelic frequency between cases and controls in Western Mexico. We reported the genotypic and allelic frequencies of seven polymorphisms in Mexican individuals from Northern and Western Mexico.

Purpose: Androgenetic alopecia (AGA) is a common type of hair loss. Previous studies indicated that the relative length of the index and ring finger (2D:4D ratio) of AGA patients was lower than control. However, the correlation between 2D:4D ratio and disease severity is unclear. In this study, we sought to evaluate the relationship between digit ratio of the right hand and AGA severity in male patients.Materials and methods: The cross-sectional study was performed. Hamilton-Norwood scale was used to assess severity. The finger lengths of the right hand were measured using a digital caliper.Results: Our study found that the lower the right-handed 2D:4D ratio, the greater the risk of developing AGA and that the severity of AGA increases with age. Patients with moderate and severe AGA (grade 3 and above) had lower 2D:4D ratios and higher average age compared with patients with mild AGA (Norwood grade 2). Patients aged ≥37.5 with a 2D:4D ratio <0.947 were six times more likely to have moderate-to-severe androgenetic alopecia compared with the reference group (OR: 6.11; 95% CI: 1.96-19.04).Conclusions: Combining 2D:4D ratio and older age may help predict the severity risk of AGA, and offer a clinically accessible, non-invasive approach for patients to easily predict their future severity.

Female patterned hair loss (FPHL) is a common form of androgenetic alopecia in women and is characterized by a hormonally directed diffuse hair loss on the scalp. Management of FPHL is well described in the literature; however, treatment of FPHL in patients with co-morbid polycystic ovarian syndrome (PCOS), an endocrinologic condition found in reproductive-aged women, has not yet been reviewed. Due to the different pathomechanism of the diseases and complexity of FPHL in PCOS patients, this study aimed to review current diagnosis and management approaches for hair loss in PCOS patients specifically and highlight the growing need for more research in this growing patient population.

Objective We designed this study to evaluate the association of serum ferritin levels with non-scarring alopecia in women. Methodology All patients were diagnosed by performing a clinical examination of the crown part width and occiput. Ludwig's classification was used to categorize the cases into grades I-III. Different laboratory tests were performed for the baseline investigation, including serum iron, total iron-binding capacity (TIBC), hemogram, and thyroid function tests. Of the 5 ml of venous blood drawn for routine biochemical tests, 3 ml was stored at -20°C for measuring serum ferritin, while the other 2 ml was sent for a complete blood count. Student's t-test, a chi-square test, and Fisher's exact test were used for comparing the variables. Results This study recruited 100 cases of alopecia. Out of them, 46% of patients were diagnosed with alopecia areata, 25% of cases reported androgenetic alopecia, and 29% of cases of telogen effluvium were also observed. We observed overall mean serum ferritin levels of 20.47±17.50 and 27.87±17.51 in the case versus the control group with a statistically significant difference of 0.005. Conclusion Our study shows that iron stores are one of the independent hazards of alopecia in non-menopausal women. Thus, proper laboratory examination is needed to manage the disease prevalence and prognosis.

Androgenetic alopecia (AGA) is a non-scarring and progressive form of hair loss occurring in both men and women. Although genetic predisposition and sex steroid hormones are the main causes, many factors remain unknown, and various extrinsic factors can negatively affect the lifespan of hair. We investigated skin-gut axis microorganisms as potential exogenous factors causing AGA, through comparative analyses of the scalp and gut microbiome in individuals with and without AGA in a Korean cohort. Using 16S rRNA gene sequencing, we characterized the scalp and gut microbiomes of 141 individuals divided into groups by sex and presence of AGA. Alpha diversity indices in the scalp microbiome were generally higher in individuals with AGA than in healthy controls. These indices showed a strong negative correlation with scalp-inhabitant bacteria (Cutibacterium and Staphylococcus), indicating that the appearance of non-inhabitant bacteria increases as hair loss progresses. No significant differences in diversity were observed between the gut microbiomes. However, bacterial functional differences, such as bile acid synthesis and bacterial invasion of epithelial cells, which are related to intestinal homeostasis, were observed. The networks of the scalp and gut microbiome were more complex and denser with higher values of the network topology statistic coefficient values (i.e., transitivity, density, and degree centrality) and more unique associations in individuals with AGA than in healthy controls. Our findings reveal a link between skin-gut microorganisms and AGA, indicating the former's potential involvement in the latter's development. Additionally, these results provide evidence for the development of cosmetics and therapeutics using microorganisms and metabolites involved in AGA.

Androgenetic alopecia (AGA) is the most common cause of hair loss in both genders with a higher psychological impact on females. Currently, topical minoxidil is the only FDA-approved treatment for female AGA and it needs life-long application and causes side effects. Cetirizine is an antihistamine that may be effective in hair loss treatment. This study aimed to compare the efficacy and safety of topical cetirizine with minoxidil (group 1) versus topical minoxidil with placebo (group 2) in female patients with AGA. This was a double-blind, randomized, controlled, parallel study conducted at Dermatology Clinic, Cairo University Teaching Hospital (Kasr- Al- Ainy), Egypt. Sixty-six patients with female AGA, aged 20-50 years, Sinclair (II-IV), were randomly assigned to one of the 2 groups for 24 weeks. The trichoscopic parameters, patients' self-assessment, side effects and global photographic assessment were evaluated. There was a statistically significant change from baseline in frontal and vertex terminal and vellus hair density (P < 0.0005) with a significant increase in vertex hair shaft thickness and average number of hairs per follicular unit in group 1 (P < 0.05). Patients reported significantly better scores in patient self-assessment in group 1 (P < 0.05). Side effects were not significantly different between groups (P > 0.05). Topical cetirizine increases hair shaft thickness and results in a higher clinical improvement from patients' perspective with a good safety profile (NCT04481412, study start date: July 2020).

Leaves of guava (Psidium guajava L.) have been used in Thai folk medicine without any supporting evidence as a traditional herbal remedy for hair loss. Androgenetic alopecia (AGA) is chronic hair loss caused by effects of androgens in those with a genetic predisposition, resulting in hair follicle miniaturization. Our objectives were to provide the mechanistic assessment of guava leaf extract on gene expressions related to the androgen pathway in well-known in vitro models, hair follicle dermal papilla cells (HFDPC), and human prostate cancer cells (DU-145), and to determine its bioactive constituents and antioxidant activities. LC-MS analysis demonstrated that the main components of the ethanolic extract of guava leaves are phenolic substances, specifically catechin, gallic acid, and quercetin, which contribute to its scavenging and metal chelating abilities. The guava leaf extract substantially downregulated SRD5A1, SRD5A2, and SRD5A3 genes in the DU-145 model, suggesting that the extract could minimize hair loss by inhibiting the synthesis of a potent androgen (dihydrotestosterone). SRD5A suppression by gallic acid and quercetin was verified. Our study reveals new perspectives on guava leaf extract's anti-androgen properties. This extract could be developed as alternative products or therapeutic adjuvants for the treatment of AGA and other androgen-related disorders.

Erosive pustular dermatosis (EPD) is a chronic inflammatory skin disorder that usually affects mature individuals. It predominantly affects the scalp and can lead to scarring alopecia. Risk factors include actinic damage and androgenetic alopecia. A traumatic insult to the skin is considered a vital trigger of the condition. EPD is a diagnosis of exclusion; thus, several neoplastic, infectious, vesiculobullous, and inflammatory conditions should be ruled out. Biopsy and clinicopathologic correlation are required to differentiate between EPD and these entities. A dysregulated, chronic immune response is considered central to the etiopathogenesis of EPD. We performed an evidence-based systematic review of the management options. There were predominantly studies with level IV and V evidence and only two with level III. Despite the responsiveness of EPD to potent topical steroids, such as clobetasol propionate, recurrence occurs after treatment withdrawal. With the available data, tacrolimus 0.1%, curettage-assisted aminolevulinic acid-photodynamic therapy, and systemic retinoids can be considered second-line options for EPD with a role in maintenance regimens. However, controlled data and more powerful studies are needed to make solid recommendations.

Platelet-rich plasma (PRP) treatment has emerged in recent years as a valuable, effective, and affordable treatment for androgenetic alopecia. Androgenetic alopecia is the most common type of alopecia, affecting both men and women, and is characterized by diminished hair follicles mainly pronounced in the frontal region and vertex. A considerable variety of PRP treatment regimens have been described so far, but there is no consensus on the standardization of PRP preparation or administration protocol. Our study was conducted on two patients to test the efficacy of a new PRP application protocol of only two treatments by using a combination of a PRP collecting device and a conventional kit. Efficacy of treatment was assessed after a 6-month follow-up by artificial intelligence (AI)-driven software on microscopic images of treated regions. An average number of hairs, cumulative hair thickness, and the number of follicular units increased in the vertex region of both patients by 30/59%, 35/53%, and 14/48%, respectively. The novel treatment regimen showed significant effectiveness in only six months.

The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin's immune response. In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers. This review provides an insight into the current literature on cannabinoid compounds as potential medicines for the treatment of skin diseases.

SARS-CoV-2 is the cause of COVID-19 disease and responsible for a pandemic since the 2020. Multiple organ involvement has been described including cutaneous symptoms. Affection of skin appendages, however, seems to be under-reported except for COVID-toes. We performed a PUBMED research for "COVID-19" OR "SARS-CoV-2" AND "skin appendages", "hair", "nails", and "skin glands" from January 2020 to April 2022. COVID toes were excluded since this symptom had extensively been discussed. The focus of this narrative review was laid on clinical presentation, association to the course of COVID-19 disease and treatment options. Skin appendages can be affected by COVID-19 disease beyond COVID-toes, both by symptomatic and asymptomatic course. Telogen effluvium, androgenetic alopecia, and alopecia areata are the most common hair disorders in COVID-19 patients. Nails are less commonly affected by COVID-19 than hair. Splinter hemorrhages and leukonychia are the most frequent findings. While sebaceous glands seem to be uninvolved, SARS-CoV-2 spike proteins have been identified in eccrine sweat glands. Alopecia areata is often seen among asymptomatic COVID-19 patients while telogen effluvium is observed in symptomatic and asymptomatic patients. The half-moon sign on the nails could be a red flag for a more severe course of COVID-19. Treatment options are summarized. Skin appendages are not spared by COVID-19. Their knowledge will help to identify asymptomatic patients and patients at risk for a more severe course of the viral disease.

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a youth-oriented tendency, but it lacks effective treatment. The binding of androgen receptor (AR) and androgen plays an essential role in the occurrence and progression of AGA. Herein, novel proteolysis targeting chimera degrader of AR (AR-PROTAC) is synthesized and integrated with dissolving microneedles (PROTAC-MNs) to achieve AR destruction in hair follicles for AGA treatment. The PROTAC-MNs possess adequate mechanical capabilities for precise AR-PROTAC delivery into the hair follicle-residing regions for AR degradation. After applying only once topically, the PROTAC-MNs achieve an accelerated onset of hair regeneration as compared to the daily application of the first-line topical drug minoxidil. Intriguingly, PROTAC-MNs via single administration still realize superior hair regeneration in AGA recrudescence, which is the major drawback of minoxidil in clinical practice. With the degradation of AR, the PROTAC-MNs successfully regulate the signaling cascade related to hair growth and activate hair follicle stem cells. Furthermore, the PROTAC-MNs do not cause systemic toxicity or androgen deficiency-related chaos in vivo. Collectively, these AR-degrading dissolving microneedles with long-lasting efficacy, one-step administration, and high biocompatibility provide a great therapeutic potential for AGA treatment.

An individual's first impression can be influenced by a number of esthetic factors, one of which is a natural hairline. The anterior hairline can be affected by various factors, such as race, age, forehead shape, and hair loss progression, similar to androgenetic alopecia. Information on the shape, hairline location on the forehead, and race are required to classify the anterior hairline. According to previous studies, the shape of the anterior hairline can be classified as round, M-shaped, rectangular, bell-shaped, or triangular. This study aimed to analyze the type of anterior hairline in Asian males without androgenetic alopecia. The subjects consisted of 461 males in China, Japan, Kazakhstan, Mongolia, the Philippines, South Korea, and Taiwan. We classified the shape of the anterior hairline into four types: M-shaped (M), rectangular (R), round (O), and wave-shaped (W). We classified the location of the anterior hairline into three types: high (H), middle (M) and low (L), according to the subjects' forehead ratio. Finally, we combined the shape and location types to devise a novel classification system for the anterior hairline type. The most common hairline types in our newly developed classification were MM (23.94%), RM (18.00%) and ML (11.04%). The least common types were OL (0.58%), OH (2.34%) and WH (2.74%). Our results will set standards for hairline shapes and locations, which will be helpful for evaluating hair loss treatment, establishing criteria and designs for reconstructive surgery, and developing camouflage makeups for the forehead hairline.

Zinc is a trace nutrient essential for the normal growth and development of human body. The main aim was to evaluate the significant association between measured zinc status in relation to different skin disorders and their severity. PubMed®, Google® Scholar™ and Cochrane© Reviews databases were searched for studies from January 2017 to June 2021, using the terms; zinc serum levels, zinc plasma levels and different dermatosis in the review, only human studies in English language were reviewed and the studies designs were controlled, cross sectional, observational and analytic types. A total of forty-eight research studies were included in this review. All studies have evaluated serum zinc in skin diseases including psoriasis, atopic dermatitis, pityriasis alba, androgenetic alopecia areata, telogen effluvium, vitiligo, melasma, acne, seborrheic dermatitis and hidradenitis suppuritiva. It was found that 33 studies had validated statistically significant differences in serum zinc levels between patients and controls. There is a predominance of low serum zinc levels in all the dermatoses reviewed. The clinical significance of this finding highlights the possible value, and need to investigate, the use of Zinc supplementation as an adjuvant therapy in the management of chronic inflammatory and autoimmune skin diseases proven to manifest altered zinc levels.

Hair loss is a widespread concern in dermatology clinics, affecting both men's and women's quality of life. Hair loss can have many different causes, which are critical to identify in order to provide appropriate treatment. Hair loss can happen due to many variables, such as genetic factors or predisposition, vitamin and mineral deficiencies, skin problems, hair growth disorders, poor diet, hormonal problems, certain internal diseases, drug use, stress and depression, cosmetic factors, childbirth, and the chemotherapy process. Treatment for hair loss varies depending on the type of alopecia, deficiency, or excess of structures such as vitamins and minerals, and also on hair and skin structure. The Mediterranean diet is characterized by low amounts of saturated fat, animal protein, and high amounts of unsaturated fat, fiber, polyphenols, and antioxidants. The main nutrients found in the Mediterranean Diet are rich in antioxidant, anti-inflammatory components. It also has an important place in hair loss treatment, since recently treatment strategies have included polyphenols and unsaturated oils more and more frequently. The goal of this work was to review published articles examining alopecia and its types, the many micronutrients that affect alopecia, and the role of the Mediterranean diet in alopecia. The literature shows that little is known about hair loss, nutritional factors, and diet, and that the data collected are conflicting. Given these differences, research into the function of diet and nutrition in the treatment of baldness is a dynamic and growing topic.