多囊卵巢综合征伴或不伴高雄激素血症患者血浆促肾上腺皮质激素和皮质醇水平研究

目的 比较多囊卵巢综合征（PCOS）伴或不伴高雄激素血症患者血浆促肾上腺皮质激素（ACTH）、皮质醇水平有无差异.方法 选择PCOS患者109例和年龄匹配的健康对照36例.测量身高、体重、腰围、臀围,计算腰臀比、体质指数,进行多毛、痤疮评分;测定黄体生成素（LH）、卵泡刺激素（FSH）、总睾酮、雌二醇、泌乳素、性激素结合球蛋白（SHBG）、脱氢表雄酮硫酸酯（DHEAS）、8am及4pm血浆ACTH和皮质醇水平;计算LH/FSH比值、游离雄激素指数（FAI）、4pm/8am ACTH比值、4pm/8am皮质醇比值、ACTH昼夜节律消失率、皮质醇昼夜节律消失率.测定空腹血糖和胰岛素,采用稳态模型法评估胰岛素抵抗指数（HOMA-IR）和胰岛分泌功能（HOMA-β）;并行卵巢超声检查.比较PCOS患者和对照组临床生化特征和ACTH、皮质醇水平的差异;将所有的PCOS患者分为高雄组（FAI≥4.5）和非高雄组（FAI ＜4.5）,比较两组的临床生化特征和ACTH、皮质醇水平.为排除肥胖因素对ACTH、皮质醇结果的影响,又选取了体质指数正常（BMI在18.5～23.9 kg/m2）的PCOS患者与健康对照进行对比.结果 （1）PCOS组较对照组LH、LH/FSH、总睾酮、DHEAS、FAI水平显著升高（P＜0.01）,ACTH-8am、ACTH昼夜节律消失率显著升高（P＜0.05）,SHBG显著降低（P＜0.01）,余指标差异无统计学意义（P＞0.05）.（2）高雄组较非高雄组总睾酮、FAI水平显著升高（P＜0.01）,ACTH-8am、ACTH-4pm和ACTH昼夜节律消失率显著升高（P＜0.05）,余指标差异无统计学意义（P＞0.05）.（3）体质指数正常的PCOS患者ACTH-8am水平、ACTH昼夜节律消失率显著高于对照组,体质指数正常的高雄组PCOS患者较非高雄组PCOS患者ACTH-8am水平仍显著升高（P＜0.05）,余指标差异无统计学意义（P＞0.05）.结论 PCOS患者存在血浆ACTH水平异常,伴高雄激素血症患者异常更加显著.     

Endocrine alterations in the aging male.

The recent increase in the elderly population, current health trends and awareness of age-related changes in the male endocrine system, have led to discussions about the role of the hormonal changes in the aging process in males. Better prevention and treatment of suboptimal health status and age-related diseases in aging men are based on an improved understanding of aging, particularly of the significance of age-associated hormonal changes. The aims of this study were 1) to evaluate the age dependence of the serum concentrations of the following important hormonal parameters in adult males using the IMMULITE 1 automated assay system (DPC, Los Angeles): testosterone, dehydro-epiandrosterone sulfate (DHEAS), estradiol (E2), sex hormone binding globulin (SHBG), lutropin (LH), follitropin (FSH), cortisol, prolactin, thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and the growth hormone-dependent parameters insulin-like growth factor (IGF-I) and IGF-binding protein-3 (IGFBP-3) and 2) to derive the following parameters: calculated free testosterone (cFT), ratio of calculated free testosterone to total testosterone (% cFT) and free androgen index (FAI). We found a significant decrease between the 21-30-year age group and the > 70-year age group for total testosterone (-42.4%), FAI (-65.5%), cFT (-60.0%), % cFT (-30.0%), DHEAS (-71.9%), E2 (-35.4%), TSH (-23.6%), IGF-I (-40.3%) and IGFBP-3 (-26.5%). Since the decreases in the FAI and cFT were greater than that of total testosterone and because these derived parameters reflect the biologically active fraction of testosterone, FAI and cFT are better markers for androgen deficiency in males. In contrast, a significant increase with age was observed for SHBG (+61.2%), LH (+40.0%), FSH (+98.3%) and cortisol (+54.2%). No significant alterations with age were observed for prolactin, fT3 and fT4. The study demonstrates that determining complete profiles of the androgenic, gonadotropic, adrenocortical, thyroid, pituitary and growth hormone/IGF endocrine axes in middle-aged and elderly men may be helpful in obtaining a correct clinical diagnosis for various hormonal disorders.     

Evaluation of direct and indirect markers to assess the androgen status in healthy males during aging

Evaluation of the male androgen status requires a marker that reflects the biologically active fraction of plasma testosterone. The serum sex hormone-binding globulin (SHBG) concentration is not suitable here because of its wide inter-individual scatter. As potential biological markers of the active testosterone fraction we compared indirect methods calculated on the basis of SHBG and total testosterone measured by fully automated IMMULITE 2000 assays (DPC, Los Angeles, CA, USA), and total testosterone alone with direct free testosterone measured by RIA (DPC). Indirect methods were the free androgen index FAI, calculated free testosterone cFT, and calculated bio-available testosterone cBT. Further androgens measured were DHEAS and androstenedione. Blood samples were collected from a cohort of 446 healthy men aged between 20-99 years. All parameters except SHBG decreased significantly during aging. The direct free testosterone assay was significantly correlated with the indirect androgen parameters. This is in accordance with earlier results using LC-MS as the gold standard method. The strongest correlation was seen with cBT/measured albumin (r=0.750), though the direct testosterone RIA does not measure the entire unbound fraction of testosterone, and total testosterone can rapidly be measured with an automated assay system. It was found that a fixed albumin concentration of 43 g/L is a reasonable calculation basis for cBT in subjects of <70 years. In the elderly >70 years or persons with known pathologies of the androgen axis, it is commendable to measure the albumin concentration individually. In conclusion, calculated bio-available testosterone (cBT) is the best marker to reflect the bioactive testosterone fraction, i.e. the androgen status in males.     

肥胖型和非肥胖型PCOS患者血清中GLP-1变化水平及其与BMI、激素水平相关性研究

目的 研究肥胖型和非肥胖型多囊卵巢综合征(PCOS)患者空腹血浆胰高血糖素样肽1(GLP-1)的分泌水平并评估其与体重指数(BMI)、激素间的相关性.方法 选取34例PCOS患者为PCOS组,16例正常健康妇女为对照组,根据BMI将PCOS组分为肥胖型PCOS患者和非肥胖型PCOS患者,采用酶联免疫法检测空腹血清GLP...     

Determination of testosterone in serum not bound by sex-hormone-binding globulin: diagnostic value in hirsute women

We compared the diagnostic value of information given by total testosterone (I), free testosterone (II), the free androgen index (III), and testosterone not bound by sex-hormone-binding globulin (SHBG) (IV) as measured by a new differential ammonium sulfate precipitation technique, each step of which is conducted at 37 degrees C. SHBG and albuminemia were also measured. To examine the clinical value of IV, we analyzed single blood samples from 15 hirsute women and 15 age-matched healthy control volunteers. Values for I, II, III, and IV testosterone were all significantly higher in the hirsute group (P less than 0.01), whereas SHBG was decreased (P less than 0.01) and albumin concentrations were similar for the two groups. Overlap between values for normal and for hirsute women was 33.3% for I, 13.3% for II, and 0% for III and IV. The presented data suggest that IV measured by ammonium sulfate precipitation is the preferred discriminator for detecting hyperandrogenism, because this assay is technically simpler and less expensive than the II assay for routine investigation. It closely reflects the pool of bioavailable testosterone; thus, its main use might be as a screening test for androgen excess in women.     

Endocrinological and metabolic characteristics in patients who are non-obese and have polycystic ovary syndrome and different types of a family history of type 2 diabetes mellitus

ObjectiveWe aimed to investigate whether patients with polycystic ovary syndrome (PCOS) and a family history (FH) of type 2 diabetes mellitus (T2DM) are at increased risk of endocrinological and metabolic abnormalities, and whether this risk differs between first-degree and second-degree relatives, and between maternal and paternal transmission.MethodsA total of 680 patients with PCOS were enrolled in this retrospective, single-center study. Endocrine and glycolipid metabolism parameters were compared.ResultsThe free androgen index (FAI), and levels of fasting blood glucose (FBG), fasting insulin (FINS), homeostatic model assessment-insulin resistance (HOMA-IR), total cholesterol (TC), and low-density lipoprotein cholesterol were significantly higher, whereas sex hormone binding globulin (SHBG) levels were significantly lower in patients with PCOS and a FH of T2DM. In patients with PCOS with a FH of T2DM in first-degree relatives, age and levels of FBG, FINS, and HOMA-IR were significantly higher than those who had a FH of T2DM in second-degree relatives. A maternal history of T2DM was associated with a higher body mass index, FAI, and TG levels, and lower SHBG levels.ConclusionsPatients with PCOS and a FH of T2DM have more severe hyperandrogenism and metabolic disorders, especially in those with maternal transmission.     

Serum leptin as an additional possible pathogenic factor in polycystic ovary syndrome

OBJECTIVES: Recent data raised the possibility that high leptin levels may contribute to infertility in some women with PCOS. DESIGN AND METHODS: To assess changes in leptin levels and its relationship to some hormonal changes (insulin, testosterone, SHBG, FSH, LH, and prolactin) associated with PCOS in obese (n = 27) and nonobese (n = 18) patients when compared to obese and nonobese normal controls (n = 20). RESULTS: Leptin concentration were significantly higher in PCOS than in controls, p < 0.05, with 81% sensitivity and 50% specificity. Whereas, high serum insulin levels were found in obese and nonobese women with PCOS, high serum leptin, FAI together with reduced SHBG were found in obese rather than nonobese PCOS women. Moreover, hyperleptinemia in PCOS women was not correlated to hyperinsulinemia (r = -0.13 and -0.4 in obese and nonobese PCOS women, respectively). In the patient's group correlation analysis between fasting serum leptin and different studied variables showed some correlation with body mass index (BMI) only (r = 0.413) suggesting that high leptin levels could be a characteristic of the obese PCOS. However, multiregression analysis showed that together with testosterone, leptin can successfully predict the presence or absence of PCOS. CONCLUSION: The potential significance of leptin for the pathophysiology of PCOS will await direct studies of the effects of exogenous leptin and/or its inhibitors on the reproductive axis of women, including those with PCOS.     

Effect of cigarette smoking on levels of bioavailable testosterone in healthy men

The effect of smoking on androgen levels is important given the recent interest in the link between low levels of androgens and the development of cardiovascular disease. Numerous studies examining the effects of cigarette smoking on the levels of total and free testosterone have reported conflicting findings, but there has been no accurate assessment of the effects of cigarette smoking on the levels of bioavailable testosterone [not bound to sex hormone-binding globulin (SHBG)]. We attempted to determine whether smoking affects the level of bioavailable testosterone. We undertook a case-control study of 25 healthy male smokers and 25 healthy never-smokers, matched by age and body mass index. Early morning levels of total, free and bioavailable testosterone, 17beta-oestradiol, SHBG and cotinine were determined and compared between the two groups. Levels of total (18.5+/-4.6 nM versus 15.1+/-4.9 nM, P=0.01) and free testosterone (462+/-91 pM versus 402+/-93 pM, P=0.03) were found to be higher in smokers compared with non-smokers respectively, as was SHBG (34.1+/-12.8 versus 28.1+/-9.0 nM, P=0.06). There were no significant differences in the levels of bioavailable testosterone (3.78+/-1.59 versus 3.51+/-1.26 nM, P=0.49) or 17beta-oestradiol (44.5+/-11.4 versus 42.3+/-11.5 pM, P=0.50) between smokers and non-smokers respectively. These data suggest that cigarette smoking has no significant effect on the biologically active fraction of testosterone, but may influence the levels of total and free testosterone through changes in the levels of SHBG.     

Lack of prolactin receptor signaling in mice results in lactotroph proliferation and prolactinomas by dopamine-dependent and -independent mechanisms

The access of testosterone and estradiol to target tissues is regulated by sex hormone-binding globulin (SHBG) in human blood. Serum SHBG levels are low in patients with hyperandrogenism, especially in association with polycystic ovarian syndrome (PCOS) and in individuals at risk for diabetes and heart disease. Here, we identify SHBG coding region variations from a compound heterozygous patient who presented with severe hyperandrogenism during pregnancy. Serum SHBG levels in this patient measured 2 years after her pregnancy were exceptionally low, and her non-protein-bound testosterone concentrations greatly exceeded the normal reference range. A single-nucleotide polymorphism within the proband's maternally derived SHBG allele encodes a missense mutation, P156L, which allows for normal steroid ligand binding but causes abnormal glycosylation and inefficient secretion of SHBG. This polymorphism was identified in four other patients with either PCOS, ioiopathic hirsutism, or ovarian failure. The proband's paternal SHBG allele carries a single-nucleotide deletion within exon 8, producing a reading-frame shift within the codon for E326 and a premature termination codon. CHO cells transfected with a SHBG cDNA carrying this mutation fail to secrete the predicted truncated form of SHBG. To our knowledge, these are the first examples of human SHBG variants linked to hyperandrogenism and ovarian dysfunction.     

金凤丸联合氯米芬治疗PCOS合并不孕患者的疗效及对雄激素水平的影响

目的观察金凤丸联合氯米芬治疗多囊卵巢综合征(PCOS)合并不孕患者的疗效及对雄激素水平的影响。方法选择2017年1月至2019年12月在该院诊治的PCOS合并不孕患者96例,根据随机数字表法将患者分为观察组和对照组,每组48例。对照组予以氯米芬治疗,观察组在对照组的基础上予以金凤丸治疗。比较两组的疗效、排卵率、妊娠率和不良反应发生率,治疗前后体质量指数(BMI)、月经周期、痤疮评分、Ferriman-Gallway(F-G)评分、卵巢体积、子宫内膜厚度、切面卵泡数、卵巢间质面积(SA)/卵巢总面积(TA),以及睾酮、硫酸脱氢表雄酮(DHEAS)、雄烯二酮和性激素结合球蛋白(SHBG)水平。结果观察组的总有效率为89.58%,对照组的总有效率为70.83%,观察组明显优于对照组(χ²=4.200,P<0.05)。观察组的妊娠率为41.67%,明显高于对照组的16.67%(P<0.05),而两组排卵率和不良反应发生率差异无统计学意义(P>0.05)。两组治疗前BMI、月经周期、痤疮评分、F-G评分、卵巢体积、子宫内膜厚度、切面卵泡数、SA/TA,以及睾酮、DHEAS、雄烯二酮和SHBG水平差异无统计学意义(P>0.05),治疗后两组的月经周期缩短,卵巢体积缩小,BMI、痤疮评分、F-G评分、切面卵泡数减少,SA/TA及睾酮、DHEAS和雄烯二酮水平明显降低(P<0.05),而子宫内膜厚度和SHBG水平均较治疗前明显增加(P<0.05),观察组与对照组比较,改善程度更为明显(P<0.05)。结论金凤丸联合氯米芬治疗PCOS合并不孕的疗效显著,能明显提高妊娠率,其机制可能与金凤丸能够降低雄激素水平有关。     

Variations in alanine aminotransferase levels within the normal range predict metabolic and androgenic phenotypes in women of reproductive age

Abstract

Background and aims. Obesity plays pathogenetic roles in nonalcoholic fatty liver disease (NAFLD) and hyperandrogenic states like polycystic ovary syndrome (PCOS). We tested the hypothesis that alanine aminotransferase (ALT), a marker of NAFLD, is associated with endocrine and metabolic abnormalities in women with normal ALT. Methods and results. Fasting glucose, insulin, total testosterone, DHEA-S, 17-hydroxyprogesterone, prolactin, leptin, soluble leptin receptor, free leptin index (FLI), lipid profile, ALT, gonadotropins, and sex hormone binding globulin (SHBG) were measured in 200 women aged 18–48 years. Beta cell function (%B), insulin sensitivity (%S) and insulin resistance were calculated using the homeostasis model assessment (HOMA-IR). Ninety-two women had PCOS (Rotterdam criteria); 64 had idiopathic hyperandrogenism; 44 were normal controls. ALT showed significant positive correlations with waist circumference (WC), systolic blood pressure, glucose, leptin, FLI, triglycerides, HOMA-IR and androgens and significant inverse correlations with leptin receptor, HDL-C, %S and SHBG. Correcting for WC and fat% showed that the associations between ALT and glucose, HOMA-IR, testosterone and free androgen index are independent of obesity. Binary logistic regression analyses showed significant association of ALT with PCOS and hyperandrogenemia. ALT ≥ 18 IU/L showed significant association with PCOS with Odds Ratio = 2.28 (95% Confidence Interval = 1.03–5.08), p = 0.043. Conclusions. In women of reproductive age, normal levels of ALT are associated with metabolic and androgenic phenotypes. We suggest a paradigm shift and extension of the routine use of ALT beyond the diagnosis of liver disease.     

性激素结合球蛋白对PCOS患者糖代谢异常及胰岛素抵抗的评估价值

[目的]探讨性激素结合球蛋白(SHBG)对多囊卵巢综合征(PCOS)患者糖代谢异常、胰岛素抵抗(IR)的评估价值.[方法]150例PCOS患者根据SHBG水平分为两组:低SHBG(SHBG＜18 nmol/L)组(n=70),正常SHBG(SHBG≥18 nmol/L)组(n=80),另选同期体检的健康者95例作为对照组.检测所有受试者血清SHBG、黄体生成激素(LH)、LH/卵泡刺激素(FSH)、空腹血糖(FPG)、空腹胰岛素(HNS)等激素、糖代谢及胰岛素抵抗(IR)指标水平,并分析SHBG与糖代谢异常、IR的相关性.[结果]低SHBG组、正常SHBG组SH-BG水平显著低于对照组(P＜0.05),雌二醇(E2)、睾酮(T)、LH、LH/FSH水平显著高于对照组(P＜0.05);正常SHBG组、低SHBG组SHBG、E、T、LH、LH/FSH水平比较差异有统计学意义(P＜0.05).低SHBG组、正常SHBG组FINS、甘油三酯(TG)、胆固醇(TC)水平显著高于对照组(P＜0.05);而与正常SHBG组相比,低SHBG组胰岛素抵抗指数(HOMA-IR)、PFG、FINS、TG、TC水平明显增高,胰岛素敏感性指数(ISI)水平显著较低(P＜0.05).相关性分析显示SHBG与HOMA-IR、HNS、PFG、LH/FSH、LH、T、TG呈负相关(P＜0.05),与ISI呈正相关(P＜0.05).[结论]低SHBG水平的PCOS患者各项性激素、糖代谢及IR相关指标更易发生失衡或紊乱,故SHBG可作为评估PCOS患者糖代谢异常及IR的重要方法.     

Reference intervals for serum testosterone,SHBG, LH and FSH in males from the NORIP project

Abstract

Reference intervals were calculated for male testosterone, SHBG, FSH and LH in serum from 599 individuals in the NORIP study. At 30 years of age, reference limits were calculated to 10.4–32.6 nmol/L testosterone, 13.5–57.4 nmol/L SHBG, 1.93–9.7 IU/L LH and 1.5–10.3 IU/L FSH, at 50 years, 9.3–31.3 nmol/L (testosterone), 18.4–75.6 nmol/L (SHBG), 2.01–10.4 IU/L (LH) and 2.04–12.4 IU/L (FSH), and at 70 years 8.6 to 30.7 nmol/L (testosterone), 27.8–101 nmol/L (SHBG), 2.22–11.2 IU/L (LH) and 2.71–14.2 IU/L (FSH). All age-+related changes were statistically significant. Reference intervals were also calculated for indices derived from testosterone, SHBG and albumin. Free androgen index, simply the ratio between testosterone and SHBG, returned results differing from the other elaborate indices, and the study thus favors use of a more elaborate index such as calculated free testosterone (CFT).     

Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat

OBJECTIVE: Previous reports of an association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markers of insulin resistance and body fat measures in 221 middle-aged nondiabetic men. RESEARCH DESIGN AND METHODS: Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07-0.1). In contrast, total testosterone correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). RESULTS: Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = -0.15 [P = 0.03], -0.14 [P = 0.03], -0.32 [P < 0.0001], and -0.38 [P < 0.0001], respectively), fasting C-peptide (r = -0.18 [P = 0.009] to -0.41 [P < 0.0001]), HOMA-IR (r = -0.15 [P = 0.03] to - 0.39 [P < 0.0001]), and body fat measures (r = -0.17 [P = 0.008] to -0.44 [P < 0.0001]). Only SHBG and total testosterone were significantly associated with fasting glucose (r = -0.20 [P = 0.003] to -0.21 [P = 0.002]). In multivariate analysis, bioavailable or free testosterone was significantly and inversely associated with insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG. CONCLUSIONS: The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat.     

Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome

BACKGROUND: The present study was designed to investigate the effects of polycystic ovary syndrome (PCOS) and of obesity on serum parathyroid hormone (RhoTauEta), 25-hydroxyvitamin D (25-OH-vitamin D), and 1,25-dihydroxyvitamin D [1,25-(OH)2-vitamin D] concentrations and the possible associations of the above calciotropic hormones with the hormonal and metabolic characteristics of the syndrome. METHODS: We studied 58 obese [body mass index (BMI)>30 kg/m2] women with PCOS, 64 overweight (BMI, 25-30 kg/m2) women with the syndrome, 169 normal-weight (BMI<25 kg/m2) women with PCOS, 29 obese controls (ovulatory women without clinical or biochemical hyperandrogenemia), 14 overweight controls, and 70 normal-weight controls. Blood samples were collected (at 0900 after an overnight fast) between the 3rd and 6th days of a menstrual cycle in the control groups and during a spontaneous bleeding episode in the PCOS groups. Circulating concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone, Delta4-androstenedione, 17alpha-hydroxyprogesterone, sex-hormone-binding globulin (SHBG), insulin, glucose, PTH, 25-OH-vitamin D, and 1,25-(OH)2-vitamin D were measured. RESULTS: Both PCOS and increased body weight had a significant positive effect on serum PTH values. PTH concentrations were significantly correlated with age, BMI, glucose, PRL, SHBG, and testosterone. Only the correlations with testosterone and PRL were BMI-independent. The effect of PCOS on PTH concentrations remained significant after adjustment for BMI, but not after adjustment for testosterone concentration. Increased body weight also had a significant negative effect on 25-OH- and 1,25-(OH)2-vitamin D concentrations, but no association with the syndrome was observed. CONCLUSIONS: The results of the present study are in agreement with previous data supporting an association of increased PTH and decreased vitamin D metabolite concentrations with obesity. Moreover, the present findings indicate, for the first time, that PTH probably is also linked to PCOS-associated hyperandrogenism.     

Unchanged androgen-binding properties of sex hormone-binding globulin in male patients with liver cirrhosis.

BACKGROUND: Men affected by liver cirrhosis frequently show clinical features of hypogonadism due to hormonal changes, in particular in the metabolism of 17beta-estradiol (E2) and testosterone (T). Sex hormone-binding globulin (SHBG), the major binding protein of these steroids in serum, is regularly elevated in such patients, with its androgen-binding properties possibly altered. In the present study, surface plasmon resonance biosensor techniques were used to determine whether the functional binding properties of this transporter are maintained in this pathology. METHODS: We selected 33 male patients with cirrhosis, Child-Pugh grade A or B, and 32 healthy males served as controls. Serum concentrations of T, E2, dehydroepiandrosterone sulfate (DHEAS) and SHBG were measured. In addition, ligand-binding properties of SHBG partially purified from sera of 23 cirrhotic patients and 20 controls were analyzed by a real-time biosensor technique using a surface-coated dihydrotestosterone derivative. RESULTS: The sensorgrams revealed that SHBG was fully bioactive in all samples investigated without any changes in binding kinetics. Moreover, total T concentrations were not significantly different in the cirrhotic patient sera (mean+/-SD 18.0+/-8.6 nmol/L) compared to controls (15.6+/-3.7; n.s.), whereas E2 was higher (152+/-60 vs. 96+/-29 pmol/L; p<0.0001) and DHEAS was lower (1493+/-1410 vs. 5099+/-2844 nmol/L; p<0.0001). CONCLUSIONS: Owing to elevated SHBG levels without changes in the steroid-binding properties in sera of cirrhotic male patients, free or bioavailable T concentrations are lower. This causes a shift of the hormonal balance in favor of E2, which exhibits a lower affinity for SHBG than androgens and accounts for the endocrine symptoms.     

多囊卵巢综合征患者的超声特征及其与内分泌指标间相关性分析

目的:比较多囊卵巢综合征(polycystic ovary syndrome,PCOS)伴与不伴高雄激素血症的患者超声特征及内分泌指标差异,并分析其间的相关性。方法:以睾酮≥1.08 ng/mL或游离睾酮≥3.18 pg/mL为标准,将126例PCOS患者分为PCOS伴高雄激素血症(hyperandrogenism,HA)(PCOS/HA组,34例)与PCOS不伴高雄激素(PCOS/NHA组,92例)。采用腔内超声检查测量并比较2组患者卵巢、子宫的灰阶及彩色多普勒二维超声参数;同时检测并比较2组患者的内分泌代谢指标,分析各超声参数与各内分泌代谢指标间的相关性。结果:PCOS/HA组患者的年龄明显小于PCOS/NHA组(P<0.01);其卵巢体积、子宫动脉阻力指数与其体质量指数呈正相关(r分别为0.64、0.57,P分别<0.01、<0.05);其卵巢间质动脉阻力指数则与体质量指数、性激素结合球蛋白、胰岛素抵抗指数、空腹血浆胰岛素水平相关(r分别为-0.46、0.55、-0.55、-0.57,P均     

Hirsutism in women. Effective therapy that is safe for long-term use

Hirsutism should be considered part of the androgen-excess syndrome unless another cause (e.g., masculinizing tumor, androgenic-drug use) can be established. Medical evaluation for transient or late-onset androgen excess, polycystic ovary syndrome, and insulin resistance is important because of the risks associated with chronic androgen excess. Treatment of insulin resistance with antiandrogen and/or insulin-lowering therapy can reduce ovarian testosterone levels and hirsutism. Simple laboratory evaluation (i.e., measuring total and free testosterone, DHEAS, and androstenedione) identifies about half of patients with hyperandrogenism. More extensive evaluation and testing are required in the remaining half. Combination therapies, specifically oral contraceptives along with antiandrogen agents, are the most effective. Studies suggest that addition of low-dose GnRH agonist therapy prolongs remission of hirsutism. Most methods produce improvement within 6 months, with continued improvement at 12 months. Successful treatment results in finer hair, decreased rate of growth, decreased need for cosmetic camouflage or removal, and improved appearance. All methods, whether used continuously or intermittently, should be considered long term.     

Effects of oral contraceptive combinations containing levonorgestrel or desogestrel on serum proteins and androgen binding

The effects of the oral contraceptive combinations 0.125 mg Org 2969 (desogestrel) (13-ethyl-11-methylene-18, 19-dinor-17α-pregn-4-en-20-yn-17—01) + 0.05 mg ethinyloestradiol (EE) and 0.125 mg levonorgestrel + 0.05 mg EE on serum sex-hormone-binding globulin (SHBG), ceruloplasmin, transcortin and ratio free testosterone over total testosterone (percentage free testosterone) and ratio free 5α-dihydrotestosterone over total 5α-dihydrotestosterone (percentage free 5α-dihydrotestosterone) were compared in healthy female volunteers.

Treatment was randomly distributed over the volunteers; 11 women received Org 2969 + EE and 11 women received levonorgestrel + EE. These combinations induced similar increases in transcortin levels (115 and 140%) and ceruloplasmin levels (115 and 123 %) after 3 months of treatment. However, the combination Org 2969 + EE induced a substantial increase (213%) in SHBG capacity after 3 months of treatment, whereas a smaller increase (80%) was observed with levonorgestrel + EE. A return to pretreatment values was observed 2 months after termination of treatment for all parameters. The difference in the effects of both preparations on SHBG was statistically significant and can be best explained by a difference in the androgenicity of the progestogens. A good correlation was observed between SHBG capacity and the reciprocal value of the percentage free testosterone and the reciprocal value of the percentage free 5α-dihydro-testosterone. These results confirm that SHBG is the major regulator of the biologically active free androgen fraction in women before, during and after combined oral contraceptive treatment.     

Effects of oral contraceptive combinations containing levonorgestrel or desogestrel on serum proteins and androgen binding

The effects of the oral contraceptive combinations 0.125 mg Org 2969 (desogestrel) (13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol) + 0.05 mg ethinyloestradiol (EE) and 0.125 mg levonorgestrel + 0.05 mg EE on serum sex-hormone-binding globulin (SHBG), ceruloplasmin, transcortin and ratio free testosterone over total testosterone (percentage free testosterone) and ratio free 5alpha-dihydrotestosterone over total 5alpha-dihydrotestosterone (percentage free 5alpha-dihydrotestosterone) were compared in healthy female volunteers. Treatment was randomly distributed over the volunteers; 11 women received Org 2969 + EE and 11 women received levonorgestrel + EE. These combinations induced similar increases in transcortin levels (115 and 140%) and ceruloplasmin levels (115 and 123%) after 3 months of treatment. However, the combination Org 2969 + EE induced a substantial increase (213%) in SHBG capacity after 3 months of treatment, whereas a smaller increase (80%) was observed with levonorgestrel + EE. A return to pretreatment values was observed 2 months after termination of treatment for all parameters. The difference in the effects of both preparations oh SHBG was statistically significant and can be best explained by a difference in the androgenicity of the progestogens. A good correlation was free testosterone and the reciprocal value of the percentage free 5 alpha-dihydrotestosterone. These results confirm that SHBG is the major regulator of the biologically active free androgen fraction in women before, during and after combined oral contraceptive treatment.