Dataset Information

Metformin-Treatment Option for Social Impairment? An Open Clinical Trial to Elucidate the Effects of Metformin Treatment on Steroid Hormones and Social Behavior

ABSTRACT: Background: Social behavior is mediated by steroid hormones, whereby various lines of evidence indicate that metformin might improve the symptoms of social withdrawal. This directly yields to the aim of the study to correlate the impact of metformin treatment on the potential alterations in steroid hormone homeostasis, which is ultimately impacting social behavior. Therefore, urinary samples of patients before and after treatment with metformin will be correlated to social behavior to elucidate potential changes in steroid hormone profiles and social behavior. Material and Methods: An observational study in healthy adults with a new indication for metformin. Steroid hormone analysis, including the most prominent androgen, estrogen, progesterone, aldosterone, corticosterone, cortisone and cortisol metabolites analyzed with gas chromatography–mass spectrometry and a questionnaire on social behavior (Autism Spectrum Questionnaire (AQ)) will be administered prior to and after around a 12-week phase of metformin treatment. Discussion: It is likely that due to different pathophysiological mechanisms such as an effect on the respiratory chain in mitochondria or via AMP-activated protein kinase, a general alteration of steroid hormone levels can be detected prior to post treatment. The encompassing measurement of steroid hormones shall give hints concerning the involvement of specific cascades yielding potential pharmacological targets for future research.

SUBMITTER: Gasser B

PROVIDER: S-EPMC9320776 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Various disturbances of social behavior, such as autism, depression, or posttraumatic stress disorder, have been associated with an altered steroid hormone homeostasis and a dysregulation of the hypothalamus-pituitary-adrenal axis. A link between steroid hormone antagonists and the treatment of stress-related conditions has been suggested. We evaluated the effects of stress induction on social behavior in the three chambers and its potential reversibility upon specific steroid hormone antagonism in mice. C57BL/6 mice were stressed twice daily for 8 days by chronic swim testing. Social behavior was evaluated by measuring, first, the preference for sociability and, second, the preference for social novelty in the three-chamber approach before and after the chronic swim test. The reversibility of behavior upon stress induction was analyzed after applying steroid hormone antagonists targeting glucocorticoids with etomidate, mineralocorticoids with potassium canrenoate, and androgens with cyproterone acetate and metformin. In the chronic swim test, increased floating time from 0.8?±?0.2 min up to 4.8?±?0.25 min was detected (p?<?0.01). In the three-chamber approach, increased preference for sociability and decreased preference for social novelty was detected pre- versus post-stress induction. These alterations of social behavior were barely affected by etomidate and potassium canrenoate, whereas the two androgen antagonists metformin and cyproterone acetate restored social behavior even beyond baseline conditions. The alteration of social behavior was better reversed by the androgen as compared with the glucocorticoid and mineralocorticoid antagonists. This suggests that social behavior is primarily controlled by androgen rather than by glucocorticoid or mineralocorticoid action. The stress-induced changes in preference for sociability are incompletely explained by steroid hormone action alone. As the best response was related to metformin, an effect via glucose levels might confound the results and should be subject to future research.

Project description:ObjectivePolycystic ovary syndrome (PCOS) is a common endocrine disorder, with potential effects on offspring both genetically and through altered intrauterine environment. Metformin, which ameliorate hormonal disturbances in non-pregnant women with PCOS is increasingly used in pregnancy. It passes the placenta, and the evidence on potential consequences for offspring endocrine development is scarce. We explore the potential effects of maternal PCOS status and intrauterine metformin exposure on offspring steroid hormone levels.DesignThis is a follow-up study of 5-10 years old children from the PregMet-study-a randomized controlled trial comparing metformin (2000 mg/day) to placebo during PCOS pregnancies. Of the 255 children invited, 117 (46%) were included.MethodsThere was no intervention in this follow-up study. Outcomes were serum levels of androstenedione, testosterone, SHBG, cortisol, 17-hydroxyprogesterone, 11-deoxycortisol and calculated free testosterone converted to gender-and age adjusted z-scores from a Norwegian reference population. These were compared in i) placebo-exposed children versus children from the reference population (z-score zero) by the deviation in z-score by one-sample t-tests and ii) metformin versus placebo-exposed children by two-sample t-tests. Holm-Bonferroni adjustments were performed to account for multiple endpoints.ResultsGirls of mothers with PCOS (n = 30) had higher mean z-scores of androstenedione (0.73 (95% confidence interval (CI) 0.41 to 1.06), p<0.0001), testosterone (0.76 (0.51 to 1.00), p<0.0001), and free testosterone (0.99 (0.67 to 1.32), p<0.0001) than the reference population. Metformin-exposed boys (n = 31) tended to have higher 11-deoxycortisol z-score than placebo-exposed boys (n = 24) (mean difference 0.65 (95% CI 0.14-1.17), p = 0.014).ConclusionMaternal PCOS status was associated with elevated androgens in 5- to 10-year-old daughters, which might indicate earlier maturation and increased risk of developing PCOS. An impact of metformin in pregnancy on steroidogenesis in children born to mothers with PCOS cannot be excluded. Our findings need confirmation in studies that include participants that have entered puberty.

Dataset Information

Metformin-Treatment Option for Social Impairment? An Open Clinical Trial to Elucidate the Effects of Metformin Treatment on Steroid Hormones and Social Behavior

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets