Impact of Lisinopril on Cardiometabolic Risk Factors in Men With Hypertension and Early-onset Androgenetic Alopecia: A Pilot Study.

ABSTRACT: Women with polycystic ovary syndrome are at a high cardiometabolic risk. Early-onset male-pattern baldness is considered the phenotypic equivalent of polycystic ovary syndrome in men. The aim of this study was to assess whether early-onset androgenetic alopecia modifies cardiometabolic effects of lisinopril in men with arterial hypertension. The study population consisted of 62 young men with grade 1 hypertension, 31 of whom were diagnosed with early-onset male-pattern baldness (group A). Thirty-one blood pressure-matched men with normal hair growth (group B) served as a control group. All participants were treated with lisinopril (10-40 mg daily). Blood pressure, glucose homeostasis markers, urinary albumin-to-creatinine ratio (UACR), as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, total and calculated free testosterone, dehydroepiandrosterone sulfate, and estradiol were assessed before lisinopril treatment and 6 months later. At baseline, levels of all cardiometabolic risk factors were higher in group A than group B. Although lisinopril reduced systolic and diastolic blood pressure, UACR, hsCRP, and fibrinogen in both study groups, these effects were stronger in group B than in group A. Only in group B, the drug decreased levels of uric acid and homocysteine, as well as improved insulin sensitivity. The impact of lisinopril on uric acid, hsCRP, fibrinogen, homocysteine, and UACR correlated weakly with its hypotensive properties, androgen levels, and insulin sensitivity. The obtained results suggest that cardiometabolic effects of lisinopril in men are less pronounced in case of coexisting early-onset androgenetic alopecia.

Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging.

Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging.

Effect of resveratrol on menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS.

AIM: The aim of this randomized trial was to find whether resveratrol could improve menstrual dysfunction, clinical signs (i.e., acne and hair loss), and the biochemical evidence of hyperandrogenism in the women with PCOS. METHODS: Women, in the age range of 18-40 years, diagnosed with PCOS, as defined by the Rotterdam criteria, and no other known cause of abnormal menstruation, were recruited. Participants were randomized based on a 1:1 ratio, to either 1000 mg resveratrol or 1000 mg placebo daily groups, for a period of 3 months. RESULTS: Seventy-eight patients were randomized: 39 to the resveratrol group and 39 to placebo. Results were analyzed according to the intention-to-treat principle. At the end of study, it was found that women who received resveratrol had a statistically higher regular menstruation rate, as compared to those who got placebo (76.47% vs. 51.61%; p = 0.03), and lower hair loss (32.10% vs. 68.00%; p = 0.009). We also found no significant differences between the two groups in terms of ovarian and adrenal androgens, sex hormone binding globulin (SHBG) levels, free androgen index (FAI), glycoinsulinemic metabolism and lipid profile. Moreover, the resveratrol treatment did not interfere with the thyroid, liver and kidney functions. The negative effect of resveratrol on the body composition was also observed, though not influencing changes in the weight, relative to the placebo group. CONCLUSION: Resveratrol improved menstrual cyclicity and hair loss, even though levels of androgens, insulin and lipids remained unchanged.

Anti-androgenetic alopecia effect of policosanol from Chinese wax by regulating abnormal hormone levels to suppress premature hair follicle entry into the regression phase.

Previously, we have demonstrated that policosanol from Chinese wax suppressed testosterone(T)-induced alopecia in mice. However, the underlying mechanism remained to be determined. Herein, we investigated the mechanism of policosanol against androgenetic alopecia (AGA). AGA was induced in Kunming mice by subcutaneous administration of testosterone propionate for 60 d. Policosanol (0.5 %, 1% or 2%) was applied topically on the back of mice. Finasteride (2%) was applied topically as a positive control. The serum T and estradiol (E2) concentrations were determined by ELISA after 28 and 60 days of treatment. The cutaneous expression or activity of key mediators of hair growth, such as alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF), was measured. MTS assay was performed to evaluate cell proliferation in cultured human dermal papilla cells (DPCs) treated with dihydrotestosterone (DHT). Western blotting was performed to evaluate the protein expression of Bax, Bcl2, TGF-ß2, caspase-9, and caspase-3. We found lower T and T/E2 ratio in mice treated with policosanol than in the model group. Policosanol suppressed premature hair follicle entry into the regression phase, as shown by improving VEGF and EGF expression and ALP activity. The MTS assay showed that policosanol markedly inhibited the apoptosis of DHT-treated DPCs. Western blotting showed that policosanol significantly reduced the protein expression of TGF-ß2, cleaved caspese-9, cleaved caspase-3, and Bax, and increased that of Bcl2. The optimal effect was obtained with 12.50 g/mL policosanol. In conclusion, policosanol prevents androgenetic alopecia by regulating hormone levels and suppressing premature hair follicle entry into the regression phase.

Laboratory Testing in Telogen Effluvium.

Telogen effluvium (TE) – a common cause of non- scarring hair loss – is managed with varying clinical protocols given the paucity of evidence-based practices.

Telogen effluvium caused by COVID-19 in Elmhurst, New York: report of a cohort and review.

The prevalence of telogen effluvium (TE) has increased during COVID-19. In this study we describe the clinical characteristics of patients with COVID-19-related TE and review the current literature on COVID-19-associated TE. We conducted a retrospective chart review of 66 patients, all of which had COVID-19 infection (confirmed by PCR or antibodies) and had either non-scarring hair loss or TE in Elmhurst, Queens. Our data suggest that this form of TE is similar to other forms of TE, after which many patients experience regrowth within several months.

The role of androgens in COVID-19.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) pandemic is a global health emergency. According to the findings, male patients with COVID-19 infection are at an increased risk for severe complications than females. The causes of this issue are unknown and are most probably multifactorial. Sexual hormones affect the immune system, so estrogen strengthens the immune system, and testosterone suppresses it. Due to the reports of the high prevalence of androgenic alopecia in hospitalized patients with COVID-19 and a higher risk of respiratory disease and increased use of allergy/asthma medications among patients with polycystic ovary syndrome (PCOS) as a hyperandrogenism condition compared with non-PCOS women, this review aimed to evaluate androgens role in COVID-19. METHODS: 42 related articles from 2008 to 2020 were reviewed with the keywords of androgens, hormonal factors, and hair loss in combination with COVID-19 in medical research databases. RESULTS: The evidence of transmembrane protease, serine 2 (TMPRSS2) expression in lung tissue, which is an androgen-regulated gene and expressed mainly in the adult prostate may interpret the increased susceptibility of the male gender to severe COVID-19 complications. Moreover, angiotensin-converting enzyme 2 (ACE-2) acts as a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and male hormones are effective in the ACE-2 passageway and simplify SARS-CoV-2 entry into host cells. CONCLUSION: Further studies on the severity of symptoms in patients with COVID-19 in other hyperandrogenism conditions compared to the control group are recommended.

Heterogeneity in amount of growth factors secreted by platelets in platelet-rich plasma samples from alopecia patients.

Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet-rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFß1), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de-identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non-cicatricial and cicatricial alopecia, a Shapiro-Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA-cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy.

Increased 25(OH)D3 level in redheaded people: Could redheadedness be an adaptation to temperate climate?

About 1-2% of European population are redheaded, meaning they synthesize more pheomelanin than eumelanin, the main melanin pigment in humans. Several mutations could be responsible for this phenotype. It has been suggested that corresponding mutations spread in Europe due to a founder effect shaped either by a relaxation of selection for dark, UV-protective phenotypes or by sexual selection in favour of rare phenotypes. In our study, we investigated the levels of vitamin D precursor 25(OH)D3 (calcidiol) and folic acid in the blood serum of 73 redheaded and 130 non-redheaded individuals. In redheaded individuals, we found higher 25(OH)D3 concentrations and approximately the same folic acid concentrations as in non-redheaded subjects. 25(OH)D3 concentrations correlated with the intensity of hair redness measured by two spectrophotometric methods and estimated by participants themselves and by independent observers. In non-redheaded individuals, 25(OH)D3 levels covaried with the amount of sun exposure and intensity of suntan while in redheaded individuals, this was not the case. It suggests that increased 25(OH)D3 levels in redheaded individuals are due to differences in physiology rather than in behaviour. We also found that folic acid levels increased with age and the intensity of baldness and decreased with the frequency of visiting tanning salons. Our results suggest that the redheaded phenotype could be an evolutionary adaptation for sufficient photosynthesis of provitamin D in conditions of low intensity of UVB radiation in central and northern parts of Europe.

Identification of a recurrent nonsense mutation in HR gene responsible for atrichia with papular lesions in two Kashmiri families.

BACKGROUND: Congenital atrichia (CA) is a rare form of irreversible alopecia with an autosomal recessive mode of inheritance. This form of hair loss is mainly associated with mutations in the human hairless (HR) gene located at chromosome 8p21.3. An additional unique feature atrichia with papular lesions (APL) comprises keratin-filled cysts known as papules. The present study aimed to uncover the underlying genetic causes of APL in two consanguineous Kashmiri families. METHODS: In the present study, two consanguineous families of Kashmiri origin with APL displaying an autosomal recessive mode of inheritance were investigated. Whole exome and Sanger sequencing followed by bioinformatic studies, variant prioritization, Sanger validation and segregation analysis was performed to find the mutation. RESULTS: A recurrent nonsense (NM_005144: c.2818C > T:p.Arg940*) mutation was detected in exon 13 of the human HR gene. CONCLUSIONS: Whole exome sequencing analysis has widely been used in the screening of single gene disorders mutations, both in research and diagnostic laboratories. Sanger sequencing alone for genes such as HR becomes expensive and time consuming. Instead, it is recommended that a patient is to screen by whole exome sequencing and then special attention first focuses on known genes of the APL phenotype. This is helpful for intime diagnosis, being more efficient and economic. The results obtained in the present study may contribute to prenatal diagnosis, carrier secreening and the genetic counseling of families with the APL phenotype in Kashmiri poplution.

Growth factor concentrations in platelet-rich plasma for androgenetic alopecia: An intra-subject, randomized, blinded, placebo-controlled, pilot study.

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, five 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 with 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 = .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 postprocessing might improve hair growth responses.

Frontal fibrosing alopecia: demographic and clinical characteristics of 490 cases.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia mostly affecting the frontotemporal hairline. Its aetiology and associated factors remain unclear. OBJECTIVE AND METHODS: An observational, cross-sectional and descriptive study was conducted in France and Germany to identify demographic and health characteristics associated with the severity of FFA. RESULTS: Of 490 included patients, 95% were female, of which 84% were postmenopausal. Age at onset of FFA symptoms ranged between 15 and 89 years, but diagnosis was frequently delayed up to 24 years. Lichen Planopilaris Activity Index scores were low (median 1.8, IQR 1.0 to 3.5). Thyroid function disorders were reported in 13% of men and 35% of women. Abnormal blood lipid levels were found in 42% of tested men and 47% of women. In the bivariate analyses, LPPAI scores were negatively correlated with abnormal testosterone (rs  = -0.775) and oestrogen values (rs  = -0.664), regular use of face cleaning products (rs  = -0.465), hair colourants (rs  = -0.679) and hairspray (rs  = -0.500). CONCLUSIONS: The most common comorbidity was thyroid disease, with proportions higher than in the European population, possibly reflecting a role of thyroid hormones in FFA pathogenesis. The association of abnormal testosterone and oestrogen values with lesser disease activity needs to be explored in further studies. Our correlation analyses do not support a role of leave-on cosmetic products in the pathophysiology of FFA.

Obstructive sleep apnea, low transferrin saturation levels, and male-pattern baldness.

BACKGROUND: There are limited data on the association between obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia, and male-pattern baldness (MPB). Low blood iron levels are reportedly associated with hypoxia and hair loss. This study explored a possible link among OSA, iron status, and MPB. METHODS: Polysomnography (PSG) and hair assessments were conducted in a cross-sectional study including 932 men aged 46-76 years. OSA was defined as an apnea-hypopnea index ≥5 by PSG evaluation and MPB as scales from IV to VII according to the Norwood-Hamilton scale classification. Serum transferrin saturation (TSA) levels were assessed. RESULTS: A total of 224 men (24%) were identified as MPB cases and 495 men (53%) as having OSA. After considering potential risk factors, OSA and other sleep-related variables were not associated with MPB. In joint analysis of OSA and family history of hair loss, men with these two factors showed a sevenfold higher multivariate odds ratio (95% confidence interval: 3.70, 12.56) for MPB than those without both of them (P < 0.05 for the interaction between OSA and family history of hair loss). TSA levels were significantly associated with MPB and OSA. OSA cases without MPB as well as MPB cases showed lower TSA levels than those with neither OSA nor MPB (P < 0.05). CONCLUSIONS: These findings suggest that OSA may be a risk factor for MPB in men who have a family history of hair loss and that low serum TSA levels associated with hypoxia may be involved in a pathway linking OSA and MPB.

Efficacy of Topical Combination of 0.25% Finasteride and 3% Minoxidil Versus 3% Minoxidil Solution in Female Pattern Hair Loss: A Randomized, Double-Blind, Controlled Study.

BACKGROUND: The relationship between female pattern hair loss (FPHL) and androgenic hormones is not well established, but some evidence indicates oral finasteride may be efficacious in FPHL. Use of a topical formulation has been proposed to minimize unwanted effects. OBJECTIVES: Our objective was to compare the efficacy and safety of topical 0.25% finasteride combined with 3% minoxidil solution and 3% minoxidil solution as monotherapy in the treatment of FPHL. METHODS: This was a prospective, randomized, double-blind study in 30 postmenopausal women with FPHL. Each participant was randomized to receive either topical 0.25% finasteride combined with topical 3% minoxidil or topical 3% minoxidil solution as monotherapy for 24 weeks. To determine efficacy, the hair density and diameter was measured and global photographic assessment was conducted at baseline and 8, 16, and 24 weeks. Side effects and serum dihydrotestosterone levels were also evaluated. RESULTS: By 24 weeks, hair density and diameter had increased in both groups, and finasteride/minoxidil was significantly superior to minoxidil solution in terms of hair diameter (p = 0.039). No systemic side effects were reported. However, serum dihydrotestosterone levels in the finasteride/minoxidil group significantly decreased from baseline (p = 0.016). CONCLUSION: A topical combination of 0.25% finasteride and 3% minoxidil may be a promising option in the treatment of FPHL with an additional benefit of increasing hair diameter. Nevertheless, as it may be absorbed percutaneously, it should be reserved for postmenopausal women. TRIAL REGISTRATION: clinicaltrials.in.th; identifier TCTR20160912002.

Telogen Effluvium With Dysesthesia (TED) Has Lower B12 Levels and May Respond to B12 Supplementation

We investigated a subtype of Telogen Effluvium associated with Dysesthesia, (TED) which was defined as the presence of Telogen Effluvium with severe itch, pain, soreness, burning, or formication in the absence of any inflammatory scalp disorder or medication associated with Telogen Effluvium or Dysesthesia. These are patients who present with a "burning" scalp or other dysesthesia associated with increased telogen hair shedding. Telogen Effluvium is not typically associated with any scalp symptoms.3 Other scalp dysesthesia studies have mentioned occasional patients in their study that were also diagnosed with Telogen Effluvium,1,2 but the clinical association of Scalp Dysesthesia and Telogen Effluvium has never been made as a distinct entity.

Hair Loss After Laparoscopic Sleeve Gastrectomy.

AIM: The aim of this study was to evaluate the prevalence of hair loss after laparoscopic sleeve gastrectomy (LSG). The effects of variables on the likelihood that patients developed hair loss were also examined. MATERIAL AND METHODS: Fifty patients who underwent LSG were enrolled in this prospective study. Demographics, hematocrit, iron, zinc, folic acid, vitamin B12, total proteins, and albumin were evaluated preoperatively and 6 months postoperatively. RESULTS: Hair loss was observed in 56% of patients and particularly in 46% in females and in 10% in males. Analysis of variance indicated statistical differences for hair loss among the groups with and without hair loss concerning preoperative zinc (p < 0.001), postoperative zinc (p < 0.001), preoperative B12 (p < 0.001), postoperative B12 (p < 0.001), postoperative folic acid (p = 0.039), and postoperative use of supplements (p < 0.001). Patients with hair loss had lower values of zinc preoperatively and postoperatively compared to patients without hair loss (0.61 vs 0.81 mcg/ml) (0.46 vs 0.73 mcg/ml) and also lower values of vitamin B12 preoperatively and postoperatively compared to patients without hair loss (243.04 vs 337.41 pg/ml) (261.54 vs 325.68 pg/ml). Interestingly, the zinc levels were normal preoperatively and lower to normal levels postoperatively and the levels of vitamin B12 were lower than normal values preoperatively in patients with hair loss. Patients with hair loss had mean lower levels of postoperative folic acid of 8 ng/ml. CONCLUSION: The prevalence of hair loss was 56% 6 months after LSG. Preoperative monitoring and counseling of these micronutrients may be a preventive and therapeutic measure.