Inhibition of human adrenal androgen secretion by ketoconazole

Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.Abbreviations CV coefficient of variation - MV mean value - SEM standard error of the mean - f female - m male - K ketoconazole - ACTH adrenocorticotropic hormone - DHEA dehydroepiandrosterone - DHEAS dehydroepiandrosterone sulfate - A androstenedione - T testosterone - F cortisol - P progesterone - H hirsutism - C Cushing's disease - EAS ectopic ACTH syndrome - ATU adrenal tumor     

Personality, manual preference and neuroendocrine reactivity in hirsute subjects

Behavioral and neuroendocrine differences may be postulated in hirsute subjects since central effects of gonadal steroids are well established. We conducted a controlled clinical study with 25 consecutive young hirsute participants compared with 20 consecutive controls. Neuropsychological evaluation included the Minnesota Multiphasic Personality Inventory (MMPI) and the Edinburgh Inventory of Manual Preference (EIMP). Neuroendocrine reactivity was assessed by the adrenocorticotropic hormone (ACTH) and cortisol responses to corticotropin releasing hormone (CRH). Hirsute participants presented a flattened personality profile with lower neurotic triad scores--146 +/- 20 versus 166 +/- 28. Left-hand preference was more common in hirsute participants--4/21 versus 0/20. Decreased ACTH [area under the curve (AUC)--36 +/-2 8 vs. 72 +/- 63 pg/ml h] and cortisol (AUC--18 +/- 4 vs. 25 +/- 10 microg/dl h) responses to CRH were found in the hirsute group. In the hirsute group, higher manual preference scores were associated with lower ACTH responses to CRH, while the opposite association was found in the control group. In the hirsute group, the hyporeactive hypothalamic-pituitary-adrenal (HPA) axis was associated with lower behavior-deviant scores, while in the control group, the hyporeactive HPA axis was associated with more psychopathology. We conclude that personality and HPA axis reactivity are different in hirsute female participants when compared with controls, with a trend for differences regarding handedness. Personality and handedness are differently associated with HPA reactivity. Distinctive features in hirsute participants are probably established very early during ontogenic development.     

肥胖与多囊卵巢综合征的相关分析

多囊卵巢综合征(PCOS)是育龄妇女最常见的临床表现高度异质性的内分泌、代谢疾病,是无排卵性不孕的主要原因之一,发病率占育龄妇女的5％～10％.肥胖与PCOS存在紧密联系.PCOS患者中,约50％存在超重或肥胖,其中大部分表现为腹型肥胖.肥胖与一系列代谢紊乱有关,特别是伴胰岛索抵抗的高胰岛素血症和高雄激素血症,两者在PCOS的病理生理过程中发挥关键作用.肥胖易加重PCOS患者的胰岛素抵抗和高雄激素血症,导致肥胖型PCOS患者更易并发2型糖尿病、心血管疾病等远期并发症,同时因此而产生的多毛、痤疮及不孕等典型表现易导致PCOS患者焦虑、抑郁等心理疾病的发生率升高.     

Concomitant dysregulation of androgen secretion and dysfunction of adipose tissue induced insulin resistance

Hyperandrogenism and hyperinsulinemia have resulted from dysfunction of the theca cell of the ovary and adipose tissue and each one potentiates the other in patients with androgen excess disorders e.g., polycystic ovary disease and idiopathic hirsutism. Possible external and/or internal triggers can produce such cellular dysfunction. There is evidence that sodium valproate acts as a trigger of cellular dysfunction and produces both hyperinsulinemia and hyperandrogenism. Therefore, the elimination of these triggers can help the patients to recover from hyperinsulinemia, insulin resistance and hyperandrogenism.     

微小RNA在多囊卵巢综合征病因学研究中的新进展

多囊卵巢综合征（PCOS）是一种常见的生殖内分泌疾病,其主要特征是高雄激素血症、稀发排卵或无排卵、卵巢多囊样改变及胰岛素抵抗。微小RNA（miRNA）是一类小分子非编码RNA,在转录后水平对靶基因进行调控。miRNA可以通过调节卵巢颗粒细胞增殖和凋亡影响卵泡发育、排卵与闭锁;通过影响雄激素的合成和释放,导致内分泌紊乱;通过调节糖代谢及胰岛素敏感性,诱导胰岛素抵抗的产生,从而参与PCOS的发病过程。现就miRNA在PCOS病因学研究中的进展进行综述。     

抗苗勒管激素与不同表型多囊卵巢综合征发病特征的相关性分析

目的探讨不同表型多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者血清抗苗勒管激素(AMH)及性激素指标水平,并评估AMH与这些指标的相关性。方法应用UNION免疫分析仪和Uni Cel Dx I800免疫分析系统检测702例PCOS患者和118例健康女性(对照组)AMH和其他性激素水平,并进行超声下窦卵泡计数(AFC)和卵巢体积测量。应用Pearson分析进行双变量相关分析。结果 PCOS患者的卵泡刺激素(FSH)低于对照组,其中无排卵或稀发排卵(OA)+高雄激素血症(HA)+多囊卵巢(PCO)组与对照组间的差异具有统计学意义(P0.05)。黄体生成素(LH)、L H/F S H、AMH均显著高于对照组。血清睾酮(T)水平在O A+H A组和O A+H A+P C O组显著升高。各组间泌乳素(P R L)、雌二醇(E2)水平无明显差异。A M H与F S H呈负相关,与L H、L H/F S H、T、A F C、左卵巢体积和右卵巢体积呈正相关。结论血清AMH浓度可以反映窦卵泡的数目和血清T的浓度高低,可作为PCOS诊断与监测指标之一,提高PCOS诊断的简便性,在临床上有广泛的应用前景。     

Isolated Transient Neonatal Clitoromegaly with Hyperandrogenism of Unknown Etiology

BackgroundNeonatal clitoromegaly is usually attributed to androgen stimulation secondary to congenital adrenal hyperplasia or in utero androgen exposure. We present a unique case of transient, isolated neonatal clitoromegaly, associated with increased androgen levels of unidentifiable cause, which spontaneously resolved when the androgen levels normalized. This is the first report where, despite an exhaustive workup, the cause of hyperandrogenism remains unknown.CaseA female infant was delivered at 25 + 5 weeks gestational age. Clitoromegaly was first documented at 3 months of age (18 mm long, 13 mm wide). There was no other evidence of virilization. There was no neonatal history of transfusions or androgen-medication exposure.Initial bloodwork documented extremely high levels of free testosterone (117 pmol/L) and dehydroepiandrosterone sulfate (DHEAS). Further tests ruled out the following diagnoses: 21-hydroxylase deficiency, 11-betahydroxylase deficiency, testicular feminization, presence of ovotesticular tissue, and androgen-secreting tumors. Maternal history ruled out in utero androgen exposure, maternal drug use, hyperandrogenism, or virilization during pregnancy, and antenatal imaging had not detected a maternal ovarian mass or adrenal tumor.The infant's androgen levels spontaneously declined, and by 4 months of age had normalized without therapy (free testosterone 8 pmol/L). At 5 months of age, the clitoral measurements normalized (10 mm long, 5 mm wide).ConclusionIn this case of a premature female infant, hyperandrogenism and clitoromegaly resolved spontaneously. Only 1 other case of hyperandrogenism and clitoromegaly that resolved spontaneously in a preterm infant has been reported. In that case, the clitoromegaly and high testosterone levels were attributed to repeated blood transfusions from an adult male. The etiology of the hyperandrogenism and resultant clitoromegaly in our case is not known.     

Intervenciones dietéticas en el tratamiento del síndrome del ovario poliquístico. Una revisión bibliográfica

Polycystic ovary syndrome (PCOS) is a female endocrinopathy recognized as a heterogeneous disorder characterized by hyperandrogenism and ovulatory dysfunction that leads to fertility problems. In addition, patients usually present with associated symptoms such as insulin resistance, glucose intolerance, central obesity and/or metabolic syndrome that can induce an increased risk of cardiovascular disease. Since one of the main goals of PCOS is to reduce the metabolic consequences related to obesity, insulin resistance, and the metabolic syndrome, targeted dietary interventions may be effective in treating PCOS.A bibliographic search has been carried out in different databases such as Web of Science, Pubmed and Google Scholar, establishing previously defined search criteria. Eleven have been chosen for full review and critical analysis. Among the different interventions that have been used, dietary strategies have been followed such as the dietary approaches to stop hypertension (DASH), modifications in carbohydrates, the inclusion of a certain food in the usual dietary pattern and/or lifestyle modifications. Of the results obtained, we highlight the improvements in body markers with a DASH diet, the benefits promoted by diets with modifications in carbohydrates, in insulin resistance and hormonal markers and favorable effects on clinical manifestations related to hyperandrogenism, fostered by soy consumption and lifestyle modifications.