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 | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Gasser Benedikt B Kurz Johann J Buerki Samuel S Mohaupt Markus M

Life (Basel, Switzerland) 20220705 7

<h4>Background</h4>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 elu ...[more]

PMID: 35888087

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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:Background: Metformin is an effective treatment option for type 2 diabetes mellitus, and it is, to this day, the most prescribed oral antiglycaemic drug. Besides its effects mainly on mitochondrial activity, an off-label use came up as a pharmaceutical for subjects with a diagnosis of polycystic ovarian syndrome (PCOS) along with altered steroid hormone homeostasis. Besides these effects, even an influence on mood and social behavior was described, leading to the aim of this case report to elucidate the effects before versus after treatment with metformin on steroid hormones and social behavior. Methods: A female patient with diagnosed PCOS was analyzed three times for steroid hormone levels. The first analysis was performed before treatment; the second, after a period of 71 days with metformin at 2 × 500 mg; and the third, after a total of 144 days with metformin at 2 × 500 mg. Spot urine probes were taken in the morning for a combined gas chromatography-mass spectrometry (GC-MS), and the steroid levels were adjusted for creatinine excretion. A questionnaire on social behavior (Autism Spectrum Questionnaire) was administered before treatment and after 71 days. Results: A decrease in all the steroid hormones measured was detected after 71 and 144 days of treatment with metformin, being more pronounced after 144 days of treatment and highly significant (p < 0.001). Furthermore, in the untreated state, the class of corticosterone metabolites showed increased values compared to the female reference values for TH-11-DH-corticosterone, TH-corticosterone, and 5a-TH-corticosterone. In the class of estrogen metabolites, increased values compared to the reference values were detected for 17b-estradiol; in the class of 11-deoxycortisol metabolites, an increase in TH-11-deoxycortisol was detected. For the class of cortisol metabolites, increased values compared to the reference values were detected for cortisone, TH-cortisone, a-cortolone, b-cortolone, 20b-dihydrocortisone, cortisol, TH-cortisol, 5a-TH-cortisol, a-cortol, 20b-dihydrocortisol, and 6b-OH-cortisol. No increases in androgen metabolites were detected. Interestingly, weight decreased from 93.4 kg to 91.3 kg after 71 days and fell to 82.7 kg after 144 days of treatment. The skeletal muscle mass was 30.1 kg at the first visit, decreasing to 29.9 kg and to 27.5 kg. No significant difference in the social behavior score from baseline to after 71 days of treatment was detected. Discussion: Metformin improved the steroid hormone profiles from levels above the upper reference values to the middle of the reference values after 71 days and to the lower ends of the reference values after 144 days of treatment. This implies not only that metformin has an effect on steroid hormone levels, but in addition that the efficacy of the pharmaceutical seems to depend on the time interval from intake. To summarize, in this patient, steroid hormones were affected but social behavior was not. If no effect of metformin on social behavior exists, this must be supported by further cases.

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.

Background

Material and methods

Discussion

Publications

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

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