ObjectivesTo compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults.DesignRandomised two-condition crossover trial.SettingLaboratory study conducted in Melbourne, Australia.Participants19 overweight/obese adults (45–75 years).InterventionsAfter an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition).Primary outcome measuresSelf-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h.Secondary outcome measuresNeuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system).ResultsDuring the active condition, fatigue levels were lower at 4 h (−13.32 (95% CI −23.48 to −3.16)) and at 7 h (−10.73 (95% CI −20.89 to −0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG).ConclusionsInterrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context.Trial registration numberACTRN12613000137796; Results.

Prolonged sitting contributes to cardiovascular disease (CVD) risk. The underlying mechanisms are unknown, but may include changes in arterial function and vasoactive mediators. We examined the effects of prolonged unbroken sitting, relative to regular active interruptions to sitting time, on arterial function in adults at increased CVD risk. In a randomized crossover trial, 19 sedentary overweight/obese adults (mean±SD 57±12 yrs), completed two laboratory-based conditions: five hours uninterrupted sitting (SIT) and; five hours sitting interrupted every 30 minutes by three minutes of simple resistance activities (SRA). Femoral artery function (flow mediated dilation; FMD), blood flow and shear rate were measured at zero hour, 30 minutes, one, two and five hours. Brachial FMD was assessed at zero and five hours. Plasma was collected hourly for measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). There was a significant decline in femoral artery FMD, averaged over five hours in the SIT condition, relative to SRA (p<0.001). Plasma ET-1 total AUC over five hours increased in the SIT condition compared to SRA (p=0.006). There was no significant difference between conditions in femoral or brachial shear rate, brachial FMD, nitrates/nitrites, VCAM-1 or ICAM-1 (p>0.05 for all). Five hours of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating ET-1 in overweight/obese adults. There is the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.

Cognitive decline leading to dementia represents a global health burden. In the absence of targeted pharmacotherapy, lifestyle approaches remain the best option for slowing the onset of dementia. However, older adults spend very little time doing moderate to vigorous exercise and spend a majority of time in sedentary behavior. Sedentary behavior has been linked to poor glycemic control and increased risk of all-cause mortality. Here, we explore a potential link between sedentary behavior and brain health. We highlight the role of glycemic control in maintaining brain function and suggest that reducing and replacing sedentary behavior with intermittent light-intensity physical activity may protect against cognitive decline by reducing glycemic variability. Given that older adults find it difficult to achieve current exercise recommendations, this may be an additional practical strategy. However, more research is needed to understand the impact of poor glycemic control on brain function and whether practical interventions aimed at reducing and replacing sedentary behavior with intermittent light intensity physical activity can help slow cognitive decline.

Hyperprolactinaemia is commonly induced by antipsychotic medications that have dopamine-blockade as their main mechanism of action. The purpose of this study was to assess the effect of antipsychotic-induced hyperprolactinaemia on hypothalamic-pituitary-gonadal axis (HPG) function.HPG axis function was assessed in 67 consecutive outpatients who were diagnosed with schizophrenia and stabilized for a period of not less than 2 years on typical antipsychotic medication, by means of clinical history, relevant questionnaires and measurement of plasma prolactin, estradiol, progesterone, testosterone, LH, FSH, sex hormone binding globulin, and TSH levels. Normative laboratory data were used to assess whether hormone levels fell within the reference range for a normal population. There was a significant correlation between dose of medication and plasma prolactin levels for the total group (P<0.001). Prolactin levels were significantly negatively associated with sex hormone levels in females (P<0.05). Males taking antipsychotic medication had a mean prolactin level of 404.1m/IU and mean gonadotrophin and sex hormone levels that fell within normal limits. The results of this study indicate that neuroleptic-induced prolactin secretion is a dose-related side effect and, in females, the level of hyperprolactinaemia is correlated with the degree of suppression of the HPG axis. Women taking long-term prolactin-raising antipsychotic medications are likely to be hyperprolactinaemic and have an associated hypogonadal state. In males, prolactin levels remain within normal limits, but at the upper end, with no apparent disturbance of reproductive hormones.

The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr (mean +/- SD). There was no significant difference in serum estradiol concentrations between cases (n = 136) and controls (n = 116). The CYP 19 genotype was significantly associated with serum estradiol (P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype (P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis (P = 0.04) and fractures (P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases (P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD (mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.

Hormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a 'normal' testosterone level is untenable.

were receiving medication known to interfere with endocrine function were omitted, as were two patients with evi-

SUMMARY.Only about 50% of women who are clinically hirsute have a raised total plasma testosterone concentration; in those cases where the total testosterone is normal the free testosterone may, in fact, be raised. Since the measurement of free testosterone is tedious, workers have used an androgen index or a calculated free testosterone concentration from the measurements of total testosterone and sex-hormone-binding globulin. We have examined the correlation between measured free testosterone, a derived free testosterone and an androgen index in hirsute women, normally menstruating women and non-hirsute women on oral contraceptive therapy. These three measures of the free testosterone concentration in blood gave similar results in all cases.It is well documented that only about half the cases of female hirsutism are associated with raised plasma total testosterone values. I, 2 The testosterone circulating in blood is mostly bound to either sex-hormone-binding globulin (SHBG) or albumin, with only about 1% unbound in female plasma.l As it has been suggested that only the unbound or free portion is available to target tissues it seems more appropriate to measure the free testosterone concentration for a more comprehensive evaluation of endocrine status. Unfortunately the methods for its determination are complex, tedious and unsuited for routine analyses.After computing a formula for the relationship between plasma free testosterone and SHBG Anderson et al. 4were able to calculate a derived free testosterone concentration from the measurements of total testosterone and SHBG concentration. Recently Carter et al. 5 showed that a free androgen index (total testosterone/SHBG) gave a better discrimination between clinically hirsute and non-hirsute patients than either of these measurements alone. However it has yet to be shown whether an empirical index or a derived free-androgen value is as efficient as measuring the actual free testosterone concentration in establishing abnormal androgen status in hirsute women.We have measured total testosterone concentration (T); free testosterone concentration (mIT); SHBG-binding capacity (as nmollL Correspondence: Dr M J Wheeler. dihydrotestosterone bound); T/SHBG ratio; and a derived free-testosterone concentration (dIT) in hirsute women, non-hirsute normallymenstruating women, and women taking oral contraceptive therapy. Patients and methodsSerum samples were collected from 18 nonhirsute normally-menstruating women (mean age 28·4 years, range 21--41; Group N), 21 non-hirsute women taking oral contraceptive therapy (mean age 24·8 years, range 18-35; Group P), and 50 hirsute female patients (mean age 28·7 years, range 20·39; Group H).Plasma T was measured by the radioimmunoassay method of Wheeler and Luther" after an initial ether extraction, and SHBG-binding capacity was measured as the amount of 14C_ dihydrotestosterone bound by a modification of the method of Rosner.7 These assays had a within-assay precision of 4·7% and 5·0% and a between-assay precision of 7·7% and 9·0%, r...