Characteristics of Adolescents with Differing Polycystic Ovary Syndrome Phenotypes

Study ObjectiveTo analyze clinical, metabolic, hormonal, and ultrasound characteristics of adolescents with polycystic ovary syndrome phenotypes.DesignWe performed a retrospective analysis of quality improvement data. We divided patients according to phenotype on the basis of clinical or biochemical diagnosis of hyperandrogenism (HA), irregular menstruation (IM), and presence or absence of polycystic ovarian morphology (PCOM) on pelvic ultrasound (PUS) images, if obtained. The 5 resulting groups were: (1) HA/IM/normal PUS, n = 28; (2) HA/PCOM, n = 10; (3) IM/PCOM, n = 18; (4) HA/IM/PCOM, n = 40; and (5) HA/IM/no PUS obtained, n = 80. We compared parameters between groups using the nonparametric Wilcoxon rank sum test.SettingBoston Children's Hospital, 2012-2016.ParticipantsOne hundred seventy-six girls and young women aged 11-25 years.InterventionsNone.Main Outcome Measures(1) Clinical, metabolic, and hormonal characteristics; and (2) PUS measurements.ResultsGroups with HA had significantly higher acne scores, Ferriman-Gallwey scores, and total and free testosterone concentrations than groups without HA. Significant differences in hemoglobin A1c were found between the IM/PCOM and HA/IM/PCOM groups (5.1% vs 5.3%; P = .01) and the IM/PCOM and HA/IM/no PUS groups (5.1% vs 5.3%; P < .01). In patients who had ultrasound performed, 49/94 (52.1%) met PCOM criteria on the basis of ovarian size, 37/94 (39.4%) on the basis of follicle number, and 27/94 (28.7%) on both; 10/94 (10.5)% had incidental findings on ultrasound, with 2 patients requiring further management.ConclusionLimited differences in clinical, metabolic, and hormonal characteristics exist between adolescents with different phenotypes of polycystic ovary syndrome, and are mostly related to the presence or absence of HA. Of patients with ultrasound examinations, only 2 had clinically actionable incidental findings.     

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。     

Polycystic ovary syndrome: Understanding the role of the brain

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and the leading cause of anovulatory infertility. Characterised by hyperandrogenism, menstrual dysfunction and polycystic ovaries, PCOS is a broad-spectrum disorder unlikely to stem from a single common origin. Although commonly considered an ovarian disease, the brain is now a prime suspect in both the ontogeny and pathology of PCOS. We discuss here the neuroendocrine impairments present in PCOS that implicate involvement of the brain and review evidence gained from pre-clinical models of the syndrome about the specific brain circuitry involved. In particular, we focus on the impact that developmental androgen excess and adult hyperandrogenemia have in programming and regulating brain circuits important in the central regulation of fertility. The studies discussed here provide compelling support for the importance of the brain in PCOS ontogeny and pathophysiology and highlight the need for a better understanding of the underlying mechanisms involved.