SAHA综合征研究进展

SAHA综合征是女性患者雄激素功能过强而引起的一组皮肤症候群,主要临床特征为皮脂溢、痤疮、多毛及雄激素脱发.该综合征可在一系列疾病导致的外周雄激素水平增高基础上发生,也可由毛囊皮脂腺组织对正常循环雄激素水平过于敏感的应答导致.临床分为特发型,卵巢型,肾上腺型,高催乳素型和高雄激素-胰岛素抵抗-黑棘皮型.应在明确病因和临床类型的基础上个体化治疗.     

多囊卵巢综合征的皮肤表现及治疗

多囊卵巢综合征在临床上已有病例报告。多发性卵巢囊肿可导致高雄激素性血症，引起痤疮、多毛、皮脂溢出、女性型脱发等症状。采用传统方法治疗痤疮无效，需采用抗雄激素疗法，必要时采用根治疗法。     

雄激素不敏感综合征2例报道并文献复习

目的探讨雄激素不敏感综合征患者的诊断和治疗特点。方法选取2018年11月至2019年8月山西医科大学第一临床医院收治的2例雄激素不敏感综合征患者作为研究对象。分析其临床诊治过程,结合文献复习,探索雄激素不敏感综合征的诊治要点。结果雄激素不敏感综合征患者的临床表型多样,主要依靠基因检测、影像学检查及相关查体确诊,社会性别确定为女性的尽早行性腺切除术,术后长期雌激素替代治疗,择期可行阴道成形术或其他整形手术。结论通过检索文献了解到雄激素不敏感综合征在临床上极为罕见,患者存在睾丸生殖细胞瘤的风险,应在青春期后尽早行性腺切除术,腹腔镜探查切除术可作为其首选手术方式。     

中草药治疗雄激素性脱发的药理与实验研究概况

雄激素性脱发(androgenetie alopecia，AGA)，又称男性型脱发(male pattern alopecia,MPA)、脂溢性脱发(sebrrheic alopecia，SA)，是皮肤科临床的常见病、多发病。现代医学认为AGA是一种雄激素依赖的常染色体显性多基因遗传性秃发，其发病与雄激素代谢增多、毛囊单位的5α-还原酶水平增高等因素直接相关。目前采用中医药治疗AGA已取得了一定的临床疗效。     

抗雄激素疗法治疗痤疮的进展

雄激素在痤疮发生过程中起着重要的作用,对于抗生素和维A酸类药物反应不佳的女性患者而言,无论其血雄激素水平是否正常,联合使用抗雄激素疗法可能是一种理想的选择,但具体机制尚不明确.抗雄激素疗法的药物可分为以下4类:雄激素受体拮抗剂、肾上腺源性雄激素阻断剂、卵巢源性雄激素阻断剂、酶抑制剂.外用抗雄激素制剂可能成为新的研究方向.概述抗雄激素治疗痤疮的机制、治疗方法以及新的研究进展.     

雄激素性脱发与冠心病

近年来研究发现雄激素性脱发(AGA)同冠心病(CHD)之间存在相关性,这种联系可能同代谢综合征、胰岛素抵抗、雄激素水平、炎症状态与血液流变学异常有关,研究结果将有助于AGA的治疗及冠心病的诊断及预防。     

痤疮与胰岛素抵抗相关性的研究进展

痤疮是好发于青春期的毛囊皮脂腺慢性炎症性疾病,激素是痤疮发生的最重要内源性因素。近年来发现,除雄激素外,胰岛素抵抗及其诱导的胰岛素和胰岛素样生长因子1水平异常也与痤疮密切相关,胰岛素与胰岛素样生长因子1通过间接刺激雄激素分泌、直接诱导角质形成细胞增殖和皮脂腺细胞脂质分泌以及炎症过程参与痤疮发生。此外,痤疮作为某些系统性疾病或综合征如多囊卵巢综合征、高雄激素血症?胰岛素抵抗?黑棘皮病综合征的重要特征以及饮食、吸烟、肿瘤与痤疮的相关性也为胰岛素抵抗在痤疮发生中的潜在作用提供了依据。     

女性型脱发及治疗进展

脱发是影响患者生活质量的一种病症,发生在女性的脱发越来越引起人们的关注,女性型脱发也称女性雄激素性脱发,可按照传统的Ludwig分类法及O1sen分类法分类,目前也有较新的BASP分类法作为参考,了解女性型脱发及临床分型将有助于其治疗.目前除延续传统治疗方法,如局部使用米诺地尔外,新型的治疗方法不断被尝试用于治疗这类患者,如抗雄激素治疗、局部使用腺苷、光疗、毛发移植等.     

女性不孕患者的PCOS研究

多囊卵巢综合征（poiycystic ovarian syndrome，PCOS）又称Stein-Leventhal综合征，是妇科一种常见的内分泌疾病，以雄激素过多和持续无排卵为临床特征，多表现为月经稀发或闭经、不孕、多毛和肥胖等一组症状，双侧卵巢呈多囊性增大改变。在育龄妇女中发病率达5％～10％。     

毛发疾病

雄激素和毛发生长；雄激素性脱发患者血清雄激素水平测定；肝肾不足型斑秃患者PBMC中Th1／TH2型细胞因子转录因子T-bet mRNA表达状况；油风治验三则；多毛症及其激光治疗的研究进展     

Skin improvement with two different oestroprogestins in patients affected by acne and polycystic ovary syndrome: clinical and instrumental evaluation

Background Despite it is accepted that acne is mostly caused by an hyper‐responsiveness of the pilo‐sebaceous unit to normal circulating androgen hormones, in a few patients, especially women, acneic lesions can be associated with increased serum androgen levels (hyperandrogenism), of which polycystic ovary syndrome (PCOS) is the most common cause. In women with acne and proven PCOS therapy with estroprogestins (EPs) can be an excellent option. Objective The aim of the study was to assess the effects of two estroprogestins (EPs), ethinyl‐estradiol (EE) 30 mcg/drospirenone (DRSP) 3 mg, and ethinyl‐estradiol (EE) 30 mcg/chlormadinone acetate (CMA) 2 mg, both on increased serum androgen levels and on several skin parameters in women affected by mild to severe acne and polycystic ovary syndrome (PCOS). Methods Fifty‐nine women were randomized to receive EE/DRSP (n = 32) or EE/CMA (n = 27) for six months. Evaluation of serum androgen levels, grading of acne and hirsutism (respectively with Pillsbury and Ferriman‐Gallwey score) and non‐invasive assessment of skin hydration, transepidermal water loss (TEWL) and skin homogeneity were performed at baseline, at 3 and 6 months (end of treatment). Results Both treatments were well tolerated and showed a significant improvement of skin and hormonal parameters, although EE/DRSP showed a more potent effect on acne and seborrhea. Conclusions Estroprogestins represent an effective and safe treatment in women with acne and polycystic ovary syndrome (PCOS). Nevertheless, the combination EE 30 mcg/DRSP 3 mg appears to be a more potent therapeutic option.     

Apert's syndrome and androgen receptor staining of the basal cells of sebaceous glands

We report two cases of Apert's syndrome, each of whom developed the severe acne in adolescence which is a feature of this disorder. Both responded to isotretinoin therapy. Immunohistochemical techniques, using a mouse monoclonal antibody, were employed to stain sebocyte androgen receptors in the two patients, and in five controls. This showed no difference in the number of cells with androgen receptor expression between the patients with Apert's syndrome and controls. These results support the concept that the underlying problem in Apert's syndrome is an abnormal sensitivity to normal circulating levels of androgens, and not an excess number of androgen receptors.     

Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action

Suberoylanilide hydroxamic acid (SAHA), an orally administered inhibitor of histone deacetylases, is currently in phase II clinical trials for cutaneous T cell lymphomas (CTCL), but the mechanism of SAHA action is unknown. In this study, we investigated the anti-tumor effects of SAHA in CTCL cell lines and freshly isolated peripheral blood lymphocytes (PBL) from CTCL patients with high percentage of circulating malignant T cells. Three cell lines (MJ, Hut78, and HH) and PBL from 11 patients and three healthy donors were treated with SAHA (1, 2.5, and 5 microM) for 24 and/or 48 h. Apoptosis was determined by flow cytometry analysis of sub-G1 hypodiploid nuclei and/or annexin V binding populations. Acetylated histones and apoptosis-associated proteins were detected by Western blotting. SAHA at 1-5 microM for 24 and 48 h induced apoptosis in a concentration- and time-dependent manner in three cell lines: MJ (0%-7% and 1%-32%), Hut78 (4%-36% and 5%-54%), and HH (4%-67% and 8%-81%). SAHA at 1-5 muM for 48 h also induced more apoptosis of patients' PBL than healthy donors' (15%-32%versus 6%-13%, p < 0.05). SAHA treatment caused an accumulation of acetylated histones (H2B, H3, and H4), an increase of p21(WAF1) and bax proteins, a decrease of Stat6 and phospho-Stat6 proteins, and activation of caspase-3 in CTCL cells. Our data suggest that selective induction of malignant T cell apoptosis and modulation of acetylated histones, p21(WAF1), bax, Stat6, and caspase-3 may underlie the therapeutic action of SAHA in CTCL patients.     

Disorder of hair growth in hyperprolactinemia

Functional hyperprolactinemia was found in five female patients, 25-35 years old, seeking medical consultation for hair loss, together with hypertrichosis (4x), disturbances of cyclic bleeding periods (4x), secondary amenorrhea (2x), galactorrhea (2x), seborrhea (2x) and persisting acne (1x). Other hormonal parameters including testosterone levels and thyroid gland function tests were unchanged. Prolactinoma was excluded by x-ray diagrams, partly also by computer tomograms of the sella. In two patients increased telogen effluvium was found by trichogram examination with some dystrophic hairs; in one patient only dystrophic hairs were seen, whereas, in two cases, hair loss was not present at the time of our clinical examination. These observations indicate that cutaneous symptoms such as seborrhea, acne, hypertrichosis/hirsutism, alopecia(= SAHA syndrome) may evidently occur in hyperprolactinemia, representing or mimicking androgen-induced skin symptoms. In such cases, therefore, evaluation of prolactin levels together with androgen blood levels and thyroid gland function tests should be performed to exclude underlying endocrinopathy.     

Acne: effect of hormones on pathogenesis and management

In the pathogenesis of acne, androgen hormones play a crucial role. In the treatment of acne, hormonal therapies provide valuable alternatives to standard modalities in selected women. Although numerous factors contribute to the development of acne, the requirement for androgens is absolute and is one that allows for effective treatments in women through inhibition of androgen expression. The two prerequisites for androgen expression at the level of the pilosebaceous unit are the presence of androgen in the form of either testosterone or dihydrotestosterone; and functioning androgen receptors. A third component may be the metabolism of androgen precursors to active androgens within pilosebaceous units. Hormonal treatment of hyperandrogenism (acne, hirsutism, androgenetic alopecia) such as that seen in polycystic ovary syndrome, centers on reduction of circulating androgen levels and androgen receptor blockade. Combination oral contraceptives represent the primary treatment modality for reducing circulating androgens from ovarian and, to a lesser degree, adrenal sources. Newer formulations may also have clinically significant androgen receptor blocking and 5alpha-reductase inhibiting effects. Newer oral contraceptives have high safety profiles and are used widely internationally for this purpose. Androgen receptor blockers currently in use include spironolactone, cyproterone acetate, and flutamide. Androgen receptor blockers are frequently combined with oral contraceptives to achieve optimal results in selected women. In women with adrenal hyperplasia, low-dose corticosteroids may be added to reduce adrenal androgen precursors. Inhibition of enzymes of androgen metabolism in the pilosebaceous unit remain largely investigational in the treatment of acne, although the benefit of 5alpha-reductase (type 2) inhibition is established in androgenetic alopecia in men. This article reviews the essentials of hormonal influence in acne pathogenesis, discusses the hormonal therapies most utilized in the treatment of acne, and the pre-treatment evaluation of women in whom hormonal therapies are being considered.     

Understanding how Age-Related Decline in Testosterone Affects Male Sexual Behavior: Neurosteroids as the Missing Piece

Purpose of Review

Age-related declines in male sexual behavior are often attributed to a well-documented decline in circulating androgens. Yet, several recent studies and metanalyses have suggested a weak relationship between circulating androgen levels and sexual behaviors, indicating that despite decreases in circulating androgens many men maintain moderate levels of sexual behavior. The lack of a strong relationship between circulating androgens and sexual dysfunction may be due to age-related changes in steroid signaling in the brain, which may be independent of circulating androgens. Androgen concentrations, synthesis, and signaling in the aging brain have been understudied. The purpose of this review is to briefly summarize our understanding of how age-related decreases in circulating androgens influence neural circuits that mediate sexual behavior and reward, and to highlight recent findings in our understanding of androgen receptors, neuroandrogens, and sexual function in healthy aged men.

Recent Findings

Age-related declines in circulating androgens weakly correlate with declines in sexual behavior, but androgen decline does not account for all the variance in sexual behavior observed among subjects. Evidence now suggests that neural nodes of the consummatory and appetitive sexual behavior circuits are capable of synthesizing androgens, independent of circulating levels of androgens. However, there remains a lack of controlled studies on neural markers of androgen signaling in healthy aged men. This ability to locally regulate androgens may compensate for lower circulating androgen levels to maintain proper sexual functioning.

Summary

To better understand age-related declines in sexual behavior, compensatory androgen synthesis in the brains of aged males should be explored further in humans and animal models. A greater understanding of these mechanisms can inform the development of pharmacotherapies that can be used to ameliorate age-related sexual dysfunction.

     

Acne‐associated syndromes: models for better understanding of acne pathogenesis

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea‐acne‐hirsutism‐androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism‐insulin resistance‐acanthosis nigricans (HAIR‐AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis‐acne‐pustulosis‐hyperostosis‐osteitis (SAPHO) and pyogenic arthritis‐pyoderma gangrenosum‐acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.     

Dermatology of androgen-related disorders

Hyperandrogenism in women can be caused by various conditions, the most prevalent of which is polycystic ovary syndrome. Common dermatologic manifestations of hyperandrogenism include hirsutism, acne, acanthosis nigricans, and androgenic alopecia. Hirsute women often have increased activity of 5 alpha-reductase, the enzyme that converts the androgen testosterone to its active metabolite, in hair follicles. Likewise, androgens affect the formation of acne by increasing sebum production from sebaceous glands in the skin. The diagnosis of polycystic ovary syndrome includes a complete history, physical examination with emphasis on evidence of androgen excess, and appropriate laboratory investigation to exclude other causes of hyperandrogenism. Treatments for the dermatologic conditions of hyperandrogenism include lifestyle modification, oral contraceptives, antiandrogens, and insulin-sensitizing medications.     

The clinical evaluation of hirsutism

Hirsutism is a disorder of excess growth of terminal hairs in androgen-dependent areas in women. Other cutaneous conditions associated with androgen excess are androgenetic alopecia, acanthosis nigricans, and acne. Hirsutism is often associated with measurably elevated androgen levels, but not in all cases. Androgens in women arise from the ovary and adrenal glands, and peripherally from skin and fat. The most common cause of hirsutism is polycystic ovarian syndrome. Patients with "idiopathic" hirsutism have normal ovulatory cycles and androgen levels. Other causes are late onset congenital adrenal hyperplasia, Cushing's syndrome, and the HAIR-AN syndrome. Pituitary, ovarian, and adrenal tumors are important, but rare causes of hirsutism. A thorough history and examination are important. Laboratory investigation is essential in women with moderate to severe, sudden onset or rapidly progressing hirsutism. Identification of the underlying etiology does not alter management, but detects patients at risk for infertility, diabetes, cardiovascular disease and endometrial carcinoma.     

HORMONAL STATUS IN POSTMENOPAUSAL ANDROGENETIC ALOPECIA

The development of androgenetic alopecia is thought to be caused by increased androgen action on hair follicles with menopause. Testosterone, estradiol and sex hormone binding globulin (SHBG) serum levels were determined in ten postmenopausal women with androgenetic alopecia and in ten sex and age matched healthy controls. No statistically significant differences were found in the hormone levels between the patients and the controls. These findings suggest that a genetically determined functional alteration of androgen receptors and/or a metabolic disturbance may exist in the hair follicle keratinocytes in androgenetic alopecia.