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Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF19, FGF21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to compare the levels of FGF19, FGF21 and lipocalin-2 between subjects with or without PCOS, and to investigate the relationship between proteins and diabetes progression. In this nested case–control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed-up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF19 (P < 0.001) and FGF21 (P = 0.022), but had lower lipocalin-2 (P < 0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P = 0.026, odds ratio (OR) (95% CI): 7.4 (1.3–43.6)), and the positive relationship between FGF21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P = 0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P = 0.026, OR (95% CI)): 2.5 (1.1–5.6)); however, this became attenuated after adjusting for waist and fasting glucose (P = 0.081). In conclusion, there is differential expression of FGF19, FGF21, and lipocalin-2 in PCOS. The serum level of FGF19, and FGF21 is associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.

Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulin-resistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. Mean weight loss was 5.2 kg (95% CI 3.0–7.5 kg, P < 0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group, peak thrombin concentration decreased by 16.71 nmol/L (95% CI 2.32–31.11, P < 0.05) and lag time and time to peak increased by 0.13 min (95% CI 0.01–0.25, P < 0.05) and 0.38 min (95% CI 0.09–0.68, P < 0.05), respectively, but there were no between-group differences. There was a trend toward 12% (95% CI 0–23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI −4 to 32, P = 0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.

Tumor cells require large amounts of energy to sustain growth. Through the mediated transport of glucose transporters, the uptake and utilization of glucose by tumor cells are significantly enhanced in the hypoxic microenvironment. Pituitary adenomas are benign tumors with high-energy metabolisms. We aimed to investigate the role of expression of glucose transporter 3 (GLUT3) and glucose transporter 1 (GLUT1) in pituitary adenomas, including effects on size, cystic change and hormone type. Pituitary adenomas from 203 patients were collected from January 2013 to April 2017, and immunohistochemical analysis was used to detect the expression of GLUT3 and GLUT1 in tumor specimens. GLUT3-positive expression in the cystic change group was higher than that in the non-cystic change group (P = 0.018). Proportions of GLUT3-positive staining of microadenomas, macroadenomas, and giant adenomas were 22.7 (5/22), 50.4 (66/131) and 54.0% (27/50), respectively (P = 0.022). In cases of prolactin adenoma, GLUT3-positive staining was predominant in cell membranes (P = 0.000006), while in cases of follicle-stimulating hormone or luteotropic hormone adenoma, we found mainly paranuclear dot-like GLUT3 staining (P = 0.025). In other hormonal adenomas, GLUT3 was only partially expressed, and the intensity of cell membrane or paranuclear punctate staining was weak. In contrast to GLUT3, GLUT1 expression was not associated with pituitary adenomas. Thus, our results indicate that the expression of GLUT3 in pituitary adenomas is closely related to cystic change and hormonal type. This study is the first to report a unique paranuclear dot-like GLUT3 staining pattern in pituitary adenomas.

Humans cannot live at very high altitude for reasons, which are not completely understood. Since these reasons are not restricted to cardiorespiratory changes alone, changes in the endocrine system might also be involved. Therefore, hormonal changes during prolonged hypobaric hypoxia were comprehensively assessed to determine effects of altitude and hypoxia on stress, thyroid and gonadal hypothalamus–pituitary hormone axes. Twenty-one male and 19 female participants were examined repetitively during a high-altitude expedition. Cortisol, prolactin, thyroid-stimulating hormone (TSH), fT4 and fT3 and in males follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone were analysed as well as parameters of hypoxemia, such as SaO₂ and paO₂ at 550 m (baseline) (n = 40), during ascent at 4844 m (n = 38), 6022 m (n = 31) and 7050 m (n = 13), at 4844 m (n = 29) after acclimatization and after the expedition (n = 38). Correlation analysis of hormone concentrations with oxygen parameters and with altitude revealed statistical association in most cases only with altitude. Adrenal, thyroid and gonadal axes were affected by increasing altitude. Adrenal axis and prolactin were first supressed at 4844 m and then activated with increasing altitude; thyroid and gonadal axes were directly activated or suppressed respectively with increasing altitude. Acclimatisation at 4844 m led to normalization of adrenal and gonadal but not of thyroid axes. In conclusion, acclimatization partly leads to a normalization of the adrenal, thyroid and gonadal axes at around 5000 m. However, at higher altitude, endocrine dysregulation is pronounced and might contribute to the physical degradation found at high altitude.

Lifestyle measures (LSMs) should be the first-line approach offered for obesity-related functional hypogonadism (FH). When LSMs fail, the role of testosterone replacement treatment (TRT) is unclear. GLP1 receptor agonist liraglutide is linked to progressive and sustained weight loss. A potential direct impact of GLP1 on hypothalamus-pituitary-testicular (HPT) axis was reported in animal models. We aimed to compare the effects of liraglutide and TRT on FH in obese men that had been poor responders to LSM, by means of reversal of FH and weight reduction. We designed a 16-week prospective randomized open-label study with 30 men (aged 46.5 ± 10.9 years, BMI 41.2 ± 8.4 kg/m², mean ± s.d.) that were randomized to liraglutide 3.0 mg QD (LIRA) or 50 mg of 1% transdermal gel QD (TRT). Sexual function and anthropometric measures were assessed. Fasting blood was drawn for determination of endocrine and metabolic parameters followed by OGTT. Model-derived parameters including HOMA_IR and calculated free testosterone (cFT) were calculated. Total testosterone significantly increased in both arms (+5.9 ± 7.2 in TRT vs +2.6 ± 3.5 nmol/L in LIRA) and led to improved sexual function. LIRA resulted in a significant increase of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P < 0.001 for between-treatment effect). Subjects treated with LIRA lost on average 7.9 ± 3.8  kg compared with a 0.9 ± 4.5  kg loss in TRT (P < 0.001). Metabolic syndrome was resolved in two patients in LIRA and in no subjects in TRT. Liraglutide was superior to TRT in improving an overall health benefit in men with obesity-associated FH after LSM failed.

Polycystic ovarian syndrome (PCOS) affects 18–22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966–April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39 IU/l (95% CI 0.09 to 0.70, P=0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37 nmol/l (95% CI 1.27 to 3.47, P<0.0001), total testosterone levels, MD −0.13 nmol/l (95% CI −0.22 to −0.03, P=0.008), androstenedione levels, MD −0.09 ng/dl (95% CI −0.15 to −0.03, P=0.005), free androgen index (FAI) levels, MD −1.64 (95% CI −2.94 to −0.35, P=0.01) and Ferriman–Gallwey (FG) score, MD −1.01 (95% CI −1.54 to −0.48, P=0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42 IU/l (95% CI 0.11 to 0.73, P=0.009), SHBG levels, MD 3.42 nmol/l (95% CI 0.11 to 6.73, P=0.04), total testosterone levels, MD −0.16 nmol/l (95% CI −0.29 to −0.04, P=0.01), androstenedione levels, MD −0.09 ng/dl (95% CI −0.16 to −0.03, P=0.004) and FG score, MD −1.13 (95% CI −1.88 to −0.38, P=0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS.