Do sexual steroids contribute to the pathomechanism of rosacea? A study of estrogen and androgen receptors in acne rosacea

Estrogen- and androgen receptor levels were investigated in the skin of 11 male and 4 female rosacea patients. No significant difference in receptor distribution or in receptor levels could be found between rosacea lesions and normal skin of the same patients. Moreover, hormone serum levels were in the normal range. Data from the present investigation suggest that rosacea formation is not governed by endocrine, although clinical and electron microscopic observations indicate a possible endocrine influence at the vascular level.     

Steroid hormone receptors in normal skin

Hormonal influences modulate various skin functions. Despite of skin manifestations indicative of increased androgenic influence, many cases show normal hormone serum levels. The target organ sensitivity of skin may be figured out by hormone receptor analysis. Our study presents data from 60 volunteer patients regarding estrogen (ER), androgen (AR), and gestagen (PgR) receptor analysis in normal skin. The highest percentages of AR and ER were found in the face of male and female patients followed by the lower extremities. Equal AR levels in both sexes indicate equal androgenic stimulability at the cellular level in both sexes. ER levels were higher in female than in male patients. PgR was negative in 14 cases. Nor could we prove any receptors in the youngest group of patients. Our results correspond with the clinical observation of different hormonal stimulability in various skin regions.     

女性更年期痤疮患者的临床特征及睾酮和雌二醇水平的检测

目的 探讨女性更年期痤疮患者血清性激素水平的变化,临床特征及治疗方法。方法 对66例患者的临床特征及治疗进行了观察;测定其中35例患者的血清睾酮和雌二醇水平。结果 患者睾酮、雌二醇与正常人对照组相比较差异无显著性,但睾酮/雌二醇显著高于正常人对照组(P<0.05)。63.6%的患者在更年期发病。皮损以上唇及颏部最多,其次为颊部、额部,多呈散在分布,以粉刺及炎性丘疹或丘脓疱疹为主,少数有炎性结节。多为轻至中度痤疮。78.8%的患者一般治疗即可治愈,其余患者用性激素治愈。结论 更年期因卵巢功能衰退,雌激素分泌减少,雌雄激素比例失衡,肾上腺源性雄激素相对过甚而导致痤疮。更年期痤疮多为轻至中度,皮损以粉刺、炎性丘疹或丘脓疱疹为主,以上唇及颏部最多。绝大多数患者一般治疗即可治愈。     

Sex hormones in lupus erythematosus

In 23 male and female patients suffering from systemic lupus erythematosus (LEV) and discoid (LEI), estradiol and androgen serum levels were determined. 11 female patients showed normal levels of estrogen. 4 out of 6 patients with LEV and 1 patient with LEI showed reduced levels of testosterone. 4 out of 5 men with LEV and 4 out of 7 men with LEI showed elevated levels of estradiol. 10 out of 12 patients showed reduced levels of testosterone. These results suggest that sexual hormones may play a part in the origination and course of LEV and LEI.     

Pituitary function and DHEA-S in male acne and DHEA-S, prolactin and cortisol before and after oral contraceptive treatment in female acne

Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.     

Expression of estrogen,androgen, and glucocorticoid receptors in recent striae distensae

Background Stretch marks or striae distensae (SD) can be considered a common skin disorder, but their physiopathogenic mechanisms have not been totally clarified. Although it is considered an esthetic complaint, it may have serious psychosocial consequences besides the local and systemic alterations of the conjunctive tissue. This study aims at assessing and quantifying the estrogen, androgen and glucocorticoid receptors in skin samples with striae and comparing with normal skin. Methods Skin samples for biopsy were obtained from eight patients with SD and eight patients without lesions. The samples were frozen at ?80 °C and underwent processing to obtain proteic extract to quantify the estrogen, androgen and glucocorticoid receptors with the Western Blot method. Results When the estrogen receptor in the skin with SD was compared with healthy skin, it was observed to have increased twice as much (P = 0.00001). The androgen and glucocorticoid receptors in the SD skin had also increased (P = 0.00015 and P = 0.00083, respectively). Conclusions These findings indicate that under certain conditions there is an increase in hormonal receptor expression, suggesting that regions that undergo greater mechanical stretching of the skin may express greater hormonal receptor activity. This activity may influence the metabolism of the extracellular matrix, causing the formation of SD. Alterations in hormone receptors occur within a well‐defined time period during the formation of SD; however, there are differences in the functionality of hormone receptors during different stages in the development of the lesions. The preliminary results appear to be relevant and represent aninitial step towards an understanding of the pathophysiology of SD.     

女性痤疮与多囊卵巢综合征的相关性研究

目的 检测成年女性痤疮患者体内性激素水平的变化,探讨其与多囊卵巢综合征（PCOS）的相关性。方法 采用放射免疫分析法,对50例痤疮患者进行血清性激素水平测定和妇科经阴道超声检查。以30例正常成年女性为对照。结果 痤疮组睾酮、二氢睾酮、脱氢表雄酮及黄体生成素水平增高,与正常对照组比较差异有高度显著性（P＜0．001或P＜0．01）;雌二醇、卵泡刺激素、孕酮水平变化不明显（P均＞0．05）。50例中有28例患PCOS。对其中10例应用达英－35治疗,可降低血清雄激素水平。结论 高雄激素血症和PCOS与成年女性痤疮有关,且是其长期不愈的重要原因。达英－35对此类痤疮有较好疗效。     

Alopecia and hirsutism*

It is not uncommon for female patients to present complaining of alopecia, greasy skin or acne and hirsutisum concommitently—the so-called androgen dependent abnormalities of skin. These are usually not associated with any specific pathological disease of the endocrine system and have been termed by Shuster (1972), primary cutaneous virilism. Only the alopecia of this type will be considered here. Since the pathogenesis of both alopecia and hirsutism have many common features from the endocrinological point of view, much of their treatment will be considered together.     

青春期后痤疮严重程度影响因素的调查分析

目的了解青春期后痤疮严重程度的主要影响因素。方法对187例患者进行问卷调查,部分患者进行血清性激素水平的检测,肾上腺和卵巢的B超检查,细菌培养及耐药性试验。结果男性、阳性家族史、油性皮肤、嗜食油腻者、经常便秘者、工作压力较大者、伴发脂溢性皮炎者的痤疮较严重;痤疮的严重程度随着年龄的增长而减轻(P<0.1)。62.5%(20/32)患者雄激素水平升高(P<0.05),6.49%(5/77)女患者合并了多囊卵巢。细菌培养的分离率由高到低依次为耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)、表皮葡萄球菌、痤疮丙酸杆菌;需氧菌的耐药率由高到低依次为青霉素、红霉素、氯洁霉素……。结论多种因素影响着青春期后痤疮的严重程度;对于顽固难治的患者,尚需考虑多囊卵巢及多重耐药菌株存在的可能。     

Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris

Abstract:  It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal androgen metabolism, and the impact of dietary factors and smoking involved in the pathogenesis of acne. The key regulator IGF-1 rises during puberty by the action of increased GH secretion and correlates well with the clinical course of acne. In acne patients, associations between serum levels of IGF-1, dehydroepiandrosterone sulphate, dihydrotestosterone, acne lesion counts and facial sebum secretion rate have been reported. IGF-1 stimulates 5α-reductase, adrenal and gonadal androgen synthesis, androgen receptor signal transduction, sebocyte proliferation and lipogenesis. Milk consumption results in a significant increase in insulin and IGF-1 serum levels comparable with high glycaemic food. Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signalling pathways of insulin receptors, IGF-1 receptor and fibroblast growth factor receptor-2b. Acne is proposed to be an IGF-1-mediated disease, modified by diets and smoking increasing insulin/IGF1-signalling. Metformin treatment, and diets low in milk protein content and glycaemic index reduce increased IGF-1 signalling. Persistent acne in adulthood with high IGF-1 levels may be considered as an indicator for increased risk of cancer, which may require appropriate dietary intervention as well as treatment with insulin-sensitizing agents.     

Congenital adrenal hyperplasia and acne in male patients

Seborrhoea is one pathogenic factor for acne. Androgens induce sebum production, and excess androgen may provoke or aggravate acne. In women an androgen disorder is frequently suspected when acne is accompanied by hirsutism or menstrual irregularities. In men acne may be the only symptom of androgen excess. We report three male acne patients in whom hormonal screening revealed irregularities of androgen metabolism suggestive of late-onset congenital adrenal hyperplasia and who benefitted from low-dose glucocorticoids. Disorders of androgen metabolism may influence acne not only in women, but also in men, and these patients may benefit from low-dose glucocorticoid therapy.     

The distribution of estrogen receptor beta is distinct to that of estrogen receptor alpha and the androgen receptor in human skin and the pilosebaceous unit

Both estrogens and androgens play important parts in skin and hair physiology, although studies of estrogen action in human skin have been rather limited. Recently, a second estrogen receptor (beta) has been identified in many nonclassical target tissues, including androgen-dependent tissues. Therefore, we have revisited the role of estrogens in human skin and hair by comparing the pattern of expression by immunohistochemistry for both estrogen receptors (alpha and beta) and the androgen receptor. Immunolocalization of androgen receptors was only seen in hair follicle dermal papilla cells and the basal cells of the sebaceous gland. Little specific staining of estrogen receptor alpha was seen anywhere except the sebaceous gland. In contrast estrogen receptor beta was highly expressed in epidermis, blood vessels, and dermal fibroblasts, whereas in the hair follicle it was localized to nuclei of the outer root sheath, epithelial matrix, and dermal papilla cells. Serial sections also showed strong nuclear expression of estrogen receptor beta in the cells of the bulge, whereas neither estrogen receptor alpha or androgen receptor was expressed. In the sebaceous gland, estrogen receptor beta was expressed in both basal and partially differentiated sebocytes in a similar pattern to estrogen receptor alpha. There was no obvious difference in the expression of either estrogen receptor in male or female nonbalding scalp skin. The results of this immunohistochemical study propose that estrogen receptor beta and not estrogen receptor alpha is the main mediator of estrogen action in human skin and the hair follicle. Further studies with androgen-dependent skin are required to determine whether estrogen receptor beta has a regulatory role on androgen receptor expression in the hair follicle in parallel with its role in other androgen-dependent tissues.     

女性痤疮患者卵泡期血清六项性激素水平的测定

目的探讨女性寻常痤疮患者体内性激素水平的改变。方法采用电化学发光免疫分析法对30例青春期女性痤疮患者及20例迟发性女性痤疮患者卵泡期血清六项性激素水平进行检测,并分别与相应年龄段的正常女性各15人作对照。结果女性青春期痤疮患者血清雌二醇水平明显低于同龄正常对照组(P<0.05);睾酮/雌二醇比值明显高于正常对照组(P<0.01);促卵泡素明显高于正常对照组(P<0.05);女性迟发性痤疮患者血清睾酮水平较相应年龄的正常对照组显著升高(P<0.05)。结论青春期女性痤疮发病的主要原因可能是由于雌激素分泌不足,使血清内睾酮水平相对增多所致。女性迟发性痤疮发病的主要原因则可能与雄激素分泌增多有关。     

云南汉族痤疮与CYP11B1基因多态性的相关性研究

【摘要】 目的 探讨CYP11B1基因多态性与痤疮发病风险之间的相关性。 方法 SNaPshot法对云南汉族403例痤疮患者（包括轻型痤疮166例 、重型痤疮237例）和207例健康对照CYP11B1基因2个单核苷酸多态性位点：rs4736312和rs4534位点进行分型,ABI 3730XL扫描分型结果。结果 rs4736312位点：男性轻型痤疮组AA、AC和CC基因型频率分别为0、20.6%、79.4%,重型痤疮组为1.8%、26.8%、71.4%,男性健康对照组为7.6%、34.8%、57.6%。A等位基因的频率分布在男性痤疮组与健康对照组间、男性轻型痤疮与健康对照组间以及男性重型痤疮与健康对照组间,差异均具有统计学意义（分别为P < 0.01、< 0.05、< 0.05）,而女性痤疮组、女性轻型痤疮组、女性重型痤疮组A、G等位基因频率分布与健康对照组相比,差异均无统计学意义（P > 0.05）。rs4534位点：男性、女性两组别的痤疮组、轻型痤疮组及重型痤疮组的AA、AG、GG基因型频率分布和A、G等位基因频率分布与各自健康对照组间,差异均无统计学意义（P > 0.05）。 结论 CYP11B1基因中rs4736312位点与云南汉族男性痤疮发病相关,而rs4534位点与云南汉族痤疮的发病无相关。 【关键词】 痤疮,寻常; 11β-羟化酶; 多态性,单核苷酸     

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.     

颧部褐青色痣与性激素相关性的研究

目的:探讨颧部褐青色痣（NFZ）患者血清性激素水平及皮损性激素受体与NFZ发病的相关性。方法: 采用免疫组化法检测雌激素受体（ER）、孕激素受体（PR）及雄激素受体（AR）在10例NFZ及蓝痣石蜡标本上的表达,同时对30例女性NFZ患者采用放射免疫法检测血清性激素（FSH 、P、 E2 、T、LH 及PRL）的水平,并将其结果与健康女性血清性激素水平加以比较。结果:NFZ皮损真皮黑素细胞免疫组化染色有5例AR阳性,ER和PR均为阴性,NFZ患者与健康人比较,血清E2、P、T、FSH、LH、PRL差异无显著性（p>0.05）。结论:NFZ的发病与性激素E2、P、T、FSH、LH、PRL水平无关,但其黑素细胞有雄激素受体。     

524例青春期后女性痤疮患者的性激素和血脂分析

目的：检测青春期后女性痤疮患者血脂和性激素水平变化情况,探讨痤疮与性激素和血脂的关系。方法：收集青春期后女性寻常痤疮患者和健康对照者,检测BMI、甘油三酯、高密度脂蛋白、垂体泌乳素、促卵泡生成素、促黄体生成素、睾酮和硫酸脱氢表雄酮水平和盆腔超声。结果：共纳入524例青春期后女性痤疮患者（轻、中、重度痤疮分别为239例,207例和78例）及50名健康对照。轻、中、重度患者垂体泌乳素、雄烯二酮和硫酸脱氢表雄酮均显著高于健康对照者（P<0.05）。379例患者无多囊卵巢综合征（PCOS）,其中高雄烯二酮患者62例,雄烯二酮水平正常者317例。较雄烯二酮正常组,高雄烯二酮组垂体泌乳素、促黄体生成素、睾酮、硫酸脱氢表雄酮及高密度脂蛋白水平升高,甘油三酯水平降低（均P<0.05）。结论：青春期后女性痤疮患者易合并多种性激素异常,其中雄激素水平升高明显。     

Adrenal androgen abnormalities in women with late onset and persistent acne

Androgens are an essential prerequisite for the development of acne. The present study was undertaken to characterize the androgen status of women with late onset and persistent acne only and, using the dexamethasone (dex) suppression test, to identify the source(s) of the androgen excess. We measured serum levels of total testosterone (T), free testosterone (FT), androstenedione ( ⁴A), dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding globulin (SHBG) in 34 healthy control subjects, in 34 women with mild acne and in 29 women with moderate or severe acne. Serum FT, DHT and DHEA-S levels in patients of both acne groups were significantly higher than those in the control subjects. The other hormone levels showed no significant differences between patients and control subjects, and there were no significant differences between the two acne groups in any of the androgen levels. In order to evaluate the ovarian and adrenal contributions to serum androgens in the acne patients, the serum levels of ⁴A, T, DHT and DHEA-S were measured prior to and following 2 weeks of dex therapy. Following the dex test, the DHT and T of adrenal origin were significantly higher in the acne patients than in the control subjects. These results suggest that, in acne patients, hyperandrogenaemia is likely to develop as a result of adrenal androgen excess. In addition, since abnormally high androgen levels are frequently seen in late onset and persistent acne, it seems that this condition is likely to be a sign of hyperandrogenism.     

Insulin‐like growth factor‐I gene polymorphism in acne vulgaris

Background Acne vulgaris is a multifactorial disease of the skin. Several studies have shown that elevated levels of serum insulin‐like growth factor‐I (IGF‐I) correlate with overproduction of sebum and acne. Recently functional relationship between IGF‐I (CA) polymorphism and circulating IGF‐I levels in adults has been reported. Aims The aim of our study was to investigate for the first time whether IGF‐I (CA) polymorphism might be involved in the pathogenesis of acne or not. Methods We included 115 acne patients and 117 healthy subjects to the study. The clinical grade of acne was assessed based on the Global Acne Grading System. Participants were questioned about diabetes mellitus, PCOS and other systemic disease. We searched for the IGF‐I (CA) 19 polymorphism in this study. The IGF‐I (CA) 19 polymorphism was performed by polymerase chain reaction. Results We categorized the IGF‐I (CA) 19 polymorphism area into three groups as lower than 192 bp, 192–194 bp and higher than 194 bp. We found that the frequency of genotype IGF‐1 (CA) 19 gene was significantly different between control and acne patients (P = 0.0002). A significant association between IGF‐I (CA) genotypes and severity of acne was found (P = 0.015). No significant difference was found between male and female patients (P > 0.05). Conclusions Our results suggest that IGF‐I (CA) 19 polymorphism may contribute to a predisposition to acne in Turkish patients.     

Neutrophil folliculitis and serum androgen levels

Pruritic folliculitis (PF) is one of the specific dermatoses of pregnancy the aetiology of which remains unknown. Several theories have been proposed, and the most commonly accepted is that it represents a hormonally induced acne, as seen in patients taking progestogenic steroids. This theory led to the proposition that serum androgen levels may be elevated in this condition, and may be causative. We studied a cohort of 125 pregnant women presenting with a variety of pregnancy dermatoses of whom 12 had PF. These women were compared with 138 pregnant control subjects without a pregnancy dermatosis to determine whether serum androgens were elevated. There was no significant elevation of serum androgens in the 12 cases of PF. There was an overall preponderance of male infants among the PF cases and birthweight of the infants was found to be reduced compared with those of controls. However, the outcome of pregnancy in all cases was favourable implying that PF has no adverse effect on foetal wellbeing.