Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma(PRP)

Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further study.Therefore,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition.Methods:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after treatment.The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification.Results:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased significantly.The results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp microbiota.In addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after treatment.Conclusions:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

The Pathogenesis and Treatment Progress of Androgenic Alopecia

Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia.

Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in teleosts.In this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)enzymes.The assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-fish.Both androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis enzymes.The Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd expression.Mechanistically,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally depleted.Collectively,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

Re-Densification Effect of Pressure-Injected Peptide-Hyaluronic Acid Combination on Male Androgenic Alopecia

Introduction: Mechanism of male androgenic alopecia (MAGA) is complex and leads to an excessive hair shedding and decreased hair density. Oral, topical, and injectable autologous treatments demonstrate ability to stimulate hair re-growth, but the response is suboptimal or plateaus off. Synthetic combination of the peptide complex and hyaluronic acid (P-HA) demonstrated hair regrowth in alopecia patients. Electronically-operated pneumatic injections (EPI) generate micro-trauma in the dermis and under wound-healing conditions may enhance regeneration effect of P-HA. Methods: Subjects seeking improvement of their male pattern hair loss (Hamilton-Norwood type 2-4) received the P-HA treatments through EPI. The course included 4 treatments every two weeks over the 8-week period. In 6 months, the hair growth was assessed comparative to baseline by global clinical photography and digital phototrichograms. The treatment safety and tolerability were documented through the whole study period. Results: Twelve men (30-45 years old) completed the treatment course with high tolerability and without adverse events. Post-treatment assessment of the previously bald areas showed improved coverage on the clinical photographs. The phototrichograms demonstrated statistically significant increase in terminal hair density by 36%, cumulative hair thickness by 37%, and follicular units by 20%;all contributing to a 38% increase in cumulated hair density (all p Conclusion: Electronic pneumatic injections are well tolerated and can be safely used for the needle-free administration of the peptide-hyaluronic acid combination in MAGA therapy. We achieved significant hair re-densification in the balding scalp. The exact role of the EPI-induced impact in the hair re-growth mechanism remains to be ascertained. .

In vivo modulation of androgen receptor by androgens

Aim: To study the effect of androgen and antiandrogen on the level of androgen receptor (AR) mRNA. Methods: The total RNA was extracted from the prostate and analyzed by slot blot analysis. The blots were hybridized with AR cDNA probe and 1A probe (internal control) and autoradiography was performed. The intensity of signal was measured with a densitometer and the ratio of AR RNA and 1A RNA was calculated. Results: Androgenic deprivation produced by castration decreased the weight of the prostate and increased the levels of AR mRNA. Treatment of the castrated rats with testostrone increased the weight of prostate and decreased the levels of AR mRNA. Treatment of normal rats with flutamide decreased the weight of the gland and increased the levels Of AR mRNA. Conclusion: Androgens produce proliferative effect on the prostate and negatively regulate the AR transcription.

Androgens and esophageal cancer: What do we know?

Significant disparities exist between genders for the development and progression of several gastrointestinal(GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors(AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome- poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.

Preli minary Study on Treat ment of Partial Androgen Deficiencyin Aging Males with Jingui Shenqi Pill (金匮肾气丸)

Objective： To observe the efficacy and safety of Jingui Shengqi Pill （金匮肾气丸, JSP） in treating partial androgen deficiency in aging males （PADAM）, and to explore the new approach in improving the quality of life in PADAM patients. Methods： Forty patients with PADAM were treated with JSP, the efficacy was evaluated with international index of erectile function （IIEF） scoring, PADAM questionnaire scoring, hormone, prostatic specific antigen （PSA）, etc., and the data before treatment were compared with those after treatment in the same group. Results： After 3 months of treatment, PADAM scoring and IIEF scoring were all significantly improved. Symptoms regarding physical ability, vasomotion, and psychical and mental condition all got improved more markedly than symptoms regarding sexual hypofunction. The serum level of testosterone was 3.85±0.36 before treatment and 5.02±0.83 after treatmnet （P〈0.05）; luteinizing hormone of 7.33±2.14 and 4.84±1.43 （P〈0.01）, follicule-stimulating hormone of 10.22±4.48 and 6.47±3.28 （P〈0.01）, respectively. The level of PSA failed to change significantly （1.94±0.55 and 2.06±0.47, P〉0.05）. Conclusion： JSP is effective and safe in treating PADAM, the mechanism of it is different from supplementing extrinsic androgen. It may have produced the effect by means of favorably regulating the condition of sex hormone to improve the balance of pituitary-sex gland axis, so it has more extensive clinical application.

The physiological and pharmacological basis for the ergogenic effects of androgens in elite sports

Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins （HDL） cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced.

One and the same androgen for all?towards designer androgens

The introduction of designer oestrogens as a treatment modality in hormone replacement in women has invited toconsider the concept of compounds with selective androgenic effects for male hormone replacement therapy. The fullspectrum of the actions of testosterone may not be necessary of even undesired for certain indications for testosteronetreatment. To define for what indications certain androgenic properties are desired and undesired more insight in basicandrogen (patho)physiology is required. There is convincing evidence that aromatization of androgenic compounds tooestrogens might be an advantage for maintenance of bone mass and it might also mitigate negative effects of androgenson biochemical parameters of cardiovascular risks; the potentially negative effects of oestrogens on prostate pathology inageing men needs further elucidation. While the role of dihydro-testosterone (DHT) for the male sexual differentiationand for pubertal sexual maturation is evident, its role in mature and ageing males seems less significant or may even beharmful. It is, however, of note that a negative effect of DHT on prostate pathophysiology is certainly not proven.For male contraception a progestational agent with strong androgenic properties might be an asset. For most of theandrogenic actions the critical levels of androgens are not well established. The latter is relevant since the large amountof androgen molecules required for its biological actions (as compared to oestrogens)is an impediment in androgenreplacement modalities. There may be room for more biopotent androgens since delivery of large amounts of androgenmolecules to the circulation poses problems for treatment modalities.

Could androgens maintain specific domains of mental health in aging men by preserving hippocampal neurogenesis

Interest surrounds the role of sex-hormones in regulating brain function outside of reproductive behaviour. Declining androgen production in aging males has been associated with cognitive impairment, depression and increased risk of developing Alzheimer＇s disease. Indication for testosterone replacement therapy is based on biochemically determined low circulating testosterone combined with manifest symptoms. However, which aspects of age-related cognitive decline are attributable to low circulating testosterone remain ambiguous. Studies examining cognition in aging men receiving testosterone replacement therapy have yielded equivocal results. The exact role of testosterone in maintaining cognitive function and the underlying neural mechanisms are largely unknown, though it would appear to be domain specific. Cladty in this area will provide clinical direction toward addressing an increasing healthcare burden of mental health decline coincident with increasing longevity. The premise that androgens contribute to maintaining aspects of mental health in aging men by preserving hippocampal neurogenesis will be used as a forum in this review to discuss current knowledge and the need for further studies to better define testosterone replacement strategies for aging male health.

Androgens/Androgen Receptor in the Management of Skin Diseases

Beyond regulation of male sexual function, the increasing evidence shows that androgens and androgen receptor (AR) have a variety of physiological and pathological effects on the skin. Skin cells express all androgen metabolizing enzymes that are required for independent skin androgen synthesis and the development of hyperandrogenic related disorders such as acne, hirsutism and androgenetic alopecia. Targeting various elements of androgen function and metabolism is the major goal of medication design for the treatment of androgen-related diseases. Antiandrogen drugs such as clascoterone, flutamide could improve conditions. Even though the involvement of androgens and AR in skin diseases has been investigated for a long time, their molecular mechanisms in skin disorders remain largely insufficient. In this review, recent studies and advances on the role of androgens/AR in several skin-related diseases and their therapeutics are systematically summarized.

Androgens, Male Hypogonadism and Traumatic Brain Injury

Traumatic brain injury (TBI) is a worldwide public health problem. Populations with a growing number of vehicles are experiencing many traumas and accidents. The highest-risk group is young men. Significant advances in neurosurgery and intensive therapy have resulted in increased survival rates of TBI patients. These higher survival rates, in turn, have led to an increasingly higher number of patients with neurological, cognitive, clinical, and social problems. This lack of knowledge about TBI has been called by some “the silent epidemic”. In recent years, studies of patients with moderate and severe TBI are increasing. Glasgow Coma Scale ≤ 8 and abnormal pupils at admission are used to determine the prognosis of patients with moderate or severe TBI. Several biomarkers such as interleukins, thiobarbituric acid reactive species, and some hormones have been studied in an effort to aid prognosis. Testosterone plays a key role in men. Thus, an understanding of androgens in TBI is essential to follow these survivors of head trauma. This review will discuss the epidemiology of TBI, its association with male hypogonadism, and possible treatments.

Impact of a physician-supervised exercise-nutrition program with testosterone substitution in partial androgen-deficient middle-aged obese men

Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity,sexual dysfunction,increase body fat,weight gain and the development of cardiac disease.Objective We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks factors.Methods Fifty-six self referred men without diabetes mellitus,hypertension,or cardiovascular disease(ages 52.3±7.8 years)were randomly selected from a large cohort.Baseline weight,body fat composition,fasting glucose,hemoglobin A1c and fasting lipid levels,as well as free and total testosterone levels were assessed.All patients were assessed and followed 6–18 months after initiation of the program.The program consisted of a low glycemic load balanced nutrition diet,a recommended structured daily exercise program of 30–60 minutes,as well as once to twice weekly intramuscular testosterone injections(113.0±27.8 mg).Results At follow up,weight was reduced from 233.9±30.0 pounds(lbs)to 221.3±25.1 lbs(P<0.001),BMI was reduced from 33.2±3.3 kg/m2 to 31.3±2.8 kg/m^(2)(P<0.0001).Total body fat was 27.1%±5.2%vs.34.3%±5.7%at baseline(P<0.0001).Fasting glucose was reduced from 95.3±14.4 mg/dL to 87.5±12.6 mg/dL(P<0.0001).Total cholesterol was reduced from 195.4±33.0 mg/dL to 172.7±35.0 mg/dL(P<0.005).No clinically significant adverse events were recorded.Conclusions Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was granted.The combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.

Defective Expression of the Gap Junction Protein Pannexin-1 Channel Contributes to the Formation of PCOS-Realted Androgenetic Alopecia

Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle.

Specific alterations of regional myocardial work in strength-trained athletes using anabolic androgenic steroids compared to athletes with genetic hypertrophic cardiomyopathy

Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.

Clinical Study on Application of Xinrun Tongluo Method Based on the Theory of Collateral Diseases in Treating Androgenic Baldness of Blood Heat Wind Dryness Syndrome

[Objectives]To explore the intervention effect of the representative formula of Xinrun Tongluo method,Liangxue Xiaofeng Powder,on the incidence of androgenic alopecia in the syndrome of blood heat and wind dryness.[Methods]A total of 72 patients with androgenic alopecia in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine from October,2022 to June,2023 were randomly divided into a control group(36 cases,treated with Western medicine)and a treatment group(36 cases,treated with Chinese herbal formula+Western medicine).The short-term and long-term efficacy of the two groups of patients was compared.[Results]The hair microscopic signs and short-term and long-term efficacy of the treatment group were significantly better than those of the control group before and after treatment,with a statistically significant difference(P<0.05).[Conclusions]The representative formula of Xinrun Tongluo method is Liangxue Xiaofeng Powder,which has better clinical efficacy as an auxiliary Western medicine in the treatment of androgenic alopecia patients with blood heat and wind dryness syndrome,and is worthy of further promotion and application in clinical practice.

Testosterone supplementation for partial androgen deficiency in middle-aged men

To evaluate the efficacy of testosterone supplementation for partial androgen deficiency in middle-aged men.Methods This prospective,double-blind,placebo-controlled,randomized clinical trial was conducted in our hospital.A total of 179 patients (mean age,41.8 years) were randomly divided into study group (n=136) and control group (mean age,n=43 years).The 136 patients in study group received andriol (80 mg,twice a day) for 3 months;while the 43 patients in control group received no special treatment.The changes of partial androgen deficiency in aging male (PADAM) scores,serum total testosterone (TT),free-T (fT) and relevant sexual hormone levels were assessed before and after treatment.Results In study group the PADAM scores at 1 and 3 months after treatment were significantly improved compared with those before treatment (P<0.01).Before treatment and 3 months after treatment,the changes of relevant hormones [TT from (11.9±0.9)nmol/L to (19.1±1.2)nmol/L,fT from (40.6±11.8) pmol/L to (75.2±17.0)pmol/L,E2 from (128.1±40.1) pmol/L to (100.6±27.5)pmol/L] also revealed that patients in study group were significantly improved after treatment (P<0.01).There were no significant changes of PADAM scores and relevant hormone levels in control group (P>0.05).Conclusion Partial androgen deficiency in middle-aged men clinically exists and testosterone supplementation for this condition is safe and effective.6 refs,4 tabs.

9例儿童雄激素不敏感综合征临床特点和遗传学特点分析

目的 分析雄激素不敏感综合征(androgen insensitivity syndrome, AIS)患者的临床资料和遗传学结果。方法 收集2017—2022年在江西省儿童医院就诊的9例AIS患者临床资料,完善相关实验室检查及性腺、腹股沟彩超,并进行基因突变检测。结果 9例患者染色体均为男性核型,其中7例患者的社会性别为女性,2例为男性;所有患者就诊原因均有腹股沟斜疝(或伴有性别模糊),均发现AR基因突变,病例1为新突变(p.R608fs*18)。66.6%(6/9)的AIS患者突变位于配体结合域(ligand binding domain, LDB),80%(4/5)的完全型雄激素不敏感综合征患者突变位于LBD,50.0%(2/4)的部分型雄激素不敏感综合征患者突变位于LBD。55.5%(5/9)AIS患者突变类型为错义突变。结论 错义突变为AR基因常见突变类型,LBD是AIS的主要突变部位,外生殖器表现为女性患者,如发现腹股沟斜疝,应常规行性腺及腹股沟彩超检查以排外AIS。

不同比例雌雄激素诱导大鼠前列腺炎症、纤维化的研究

目的研究不同比例浓度雌雄激素对前列腺组织炎症、纤维化程度的影响。方法取4月龄SD雄性大鼠84只,随机分并对78只大鼠行双侧睾丸切除手术去势模型,同时对去势大鼠皮下注射不同浓度雌雄激素,1个月后取大鼠前列腺组织,通过HE染色和Masson染色分别观察前列腺炎症及纤维化程度。结果雌激素能诱导前列腺组织炎症浸润及纤维化,且随雌激素浓度增加而加重,而雄激素在一定程度上能缓解炎症、纤维化程度,其缓解程度与雄激素浓度比例正相关。结论雌激素能诱导前列腺组组织炎症、纤维化,雄激素能改善前列腺炎症及纤维化,其作用与浓度密切相关。