Investigating the Endocrine-metabolic-immunological Axis During the Female Menstrual Cycle by Functional Genomics

Study Overview
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Brief Summary
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As there are fluctuations in the hormonal balance during the menstrual cycle, it is assumed that due to the interaction between the hormonal system and the immune system, some diseases might be worsened in the course of a cycle. This interaction is particularly important during the phases of the cycle when the corpus luteum is formed and secretes estrogens and progesterone (secretion phase, luteal phase), as well as during menstruation itself. To date, there is no comprehensive review regarding the molecular signaling pathways that are active during and influence the menstrual cycle. The menstrual cycle influences blood glucose levels. Women are subject to greater fluctuations in blood glucose levels than men according to the phases of the menstrual cycle (menstrual phase, proliferative phase, ovulation, luteal phase). Since there are contradictory results regarding the influence of the menstrual cycle on glucose metabolism, the glucose and insulin response, as well as the glucose-dependent intestinal hormone glucagon-like peptide 1(GLP-1) after food intake are determined in the study presented here using an oral glucose tolerance test.

Detailed Description
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Within the menstrual cycle there are strong hormonal fluctuations. Therefore, it is obvious that the interaction between the endocrine system and the immune system play an important role in the progression of different diseases during the course of a cycle, especially during the luteal phase and menstruation. The molecular signaling pathways that are active during the menstrual cycle and have an influence on it have not been extensively elucidated to date. Furthermore, glucose homeostasis, on which the female cycle also can have an influence, is part of the research. Study results show that when an oral glucose tolerance test (oGTT) is performed, women are subject to greater fluctuations in blood glucose levels than men. This seems to be dependent on the phases of the female menstrual cycle. It was shown that glucose metabolism was impaired in the luteal phase. Contradictory to this, in another study no significant influence on glucose metabolism by the menstrual cycle could be detected. Based on these equivocal results, in this study the postprandial glucose and insulin response, as well of the glucose-dependent gut hormone GLP-1 in the different cycle phases will be examined. For this purpose, an intervention study is set up in which blood samples are taken at five different time points and the subjects participate in an oGTT at four of these different time points in their individual menstrual cycle. Furthermore, anthropometry measures and body composition will be determined with the help of Bodpod and bioelectrical impedance analysis (BIA) measurements. A diary will also be kept during the entire study duration in order to record the habitual diet. In addition, different subgroups are studied: continuous measurement of body temperature or glucose levels using sensors, continuous collection of stool samples and documentation of daily nutrition using an app. To account for regular daily variations in immunological measurements that are not related to the menstrual cycle, a cohort of healthy, male individuals will be examined.

Official Title
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Investigating the Endocrine-metabolic-immunological Axis During the Female Menstrual Cycle by Functional Genomics

Conditions
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Menstrual Cycle

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men Age between 20 and 30 years BMI: 18,5 - 25 kg/m2 Written informed consent to participate in the study if applicable: Regular menstruation in the last 6 months if applicable: Cycle length between 21 and 35 days for each cycle in the last 6 months (self-reported). Exclusion Criteria: Smoking Mental illness Chronic illnesses Antibiotic therapy 3 weeks before the start of the study Alcohol, medication and/or drug abuse (BTMG-liable or other psychotropic substances) Participation in another clinical study at the same time or within the last 30 days Hospitalization in the last 3 months Inflammatory condition in the last 30 days or during the course of the study Other exclusion criteria at the discretion of the physician/investigator History of infection with SARS-CoV2 before or during the study period Regular physical activity with very high intensity (athletes) Coagulation disorders Planning a restrictive diet for weight loss or medical reasons in the next 3 months Gastrointestinal disease associated with malabsorption (e.g., Crohn's disease) Whole blood donation within the last 3 months (women) or last 2 months (men) Known infertility Infection with Chlamydia in the past if applicable: Pregnancy, lactation if applicable: Use of any contraceptive (hormonal or chemical contraception) within and during the 6 months prior to study entry. An exception are mechanical contraceptives such as condoms if applicable: planning pregnancy in the next 3 months if applicable: attempted conception in the past 6 months if applicable: smear test with abnormal findings in the past 6 months (without subsequent abnormal findings) if applicable: untreated gynecological infection or of the urogenital tract in the last 6 months if applicable: gynecological surgery in the last 12 months if applicable: current or past other gynecologic complaints

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| characterisation of peripheral immune cells | scRNA-seq, PRECISE platform | through study completion, an average of 1 year | 
| gonadotropins | concentration of luteinizing hormone (LH), follicle stimulating hormone (FSH) (pmol/l), central laboratory, University Hospital Bonn (UKB) | through study completion, an average of 1 year | 
| sex hormones | concentration of estrogen, progesterone, testosterone (pmol/l), central laboratory, UKB Bonn | through study completion, an average of 1 year | 
| cytokines | concentration of cytokines in blood (pmol/l) | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose | fasting and postprandial (after OGTT) blood glucose concentration (mg/dl), Biosen C-line, EKF | during the procedure | 
| insulin | fasting and postprandial (after OGTT) blood insulin concentration (mU/l), central laboratory, UKB Bonn | through study completion, an average of 1 year | 
| gut microbiome | stool: bacterial composition of gut microbiota (diversity, taxonomy) | through study completion, an average of 1 year | 
| body height | body height (cm), measured with stadiometer (seca scale 704, seca GmbH und Co. KG, Hamburg) | baseline | 
| Habitual diet | Food frequency questionnaire (FFQ), Nutrient (mg/day) and food intake (portions/day) | baseline | 
| blood pressure | blood pressure (mmHG) and heart rate (bpm), measured with Boso-carat professional, Bosch und Sohn GmbH und Co. KG, Jungingen) | during the procedure | 
| body composition | body composition (fat mass and fat free mass in %), measured with BIA and BOD POD | during the procedure | 
| body weight | body weight (kg), measured with electrical scale (seca scale 704, seca GmbH und Co. KG, Hamburg) | during the procedure | 
| circumference | circumference of waist and hip (cm), measure tape | during the procedure | 
| GLP-1 | fasting and postprandial (after OGTT) blood GLP-1 concentration (pmol/l), measured by ELISA | through study completion, an average of 1 year | 
| intestinal transit time | intestinal transit time (hours), measured by the blue-poo method | baseline | 
| stool consistency | questionnaire assessing stool consistency (Bristol-stool-scale), score from 1-7 | baseline | 
| continuous measurement of body temperature | iButton (Moritz Fuchs Elektronik, Weingarten) | during the procedure | 
| continuous measurement of glucose levels | FreeStyle Libre 3 sensor (Abbott GmbH, Wiesbaden) | during the procedure | 
| continuous collection of stool samples | continuous measurement of bacterial composition of gut microbiota (diversity, taxonomy) | during the procedure | 
| documentation of daily nutrition | Perfood Labs App (Perfood GmbH, Lübeck), macronutrient composition (mg) | during the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune system & metabolism