Clinical trial NCT03581201: The Relationship of the Intestinal Microbiome and the Menstrual Cycle
Official title: The Relationship of the Intestinal Microbiome and the Dynamic Changes of Sex Hormone Concentrations in Women at Childbearing Age
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sex Hormones
Microbial Colonization
Keywords: intestinal microbiome
oral contraceptives
estrogens
bacterial population
hormone status
glucose profiles
lipid parameters
body composition
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: University of Vienna
First posted: 2018-07-10
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: In total, 20 patients (10 subjects with oral contraceptives and 10 subjects without oral contraceptives or any contraceptive at all) between 18 and 40 years and a body mass index (BMI) between 18 and 24 kg/ m² will be examined in this study.

Brief summary: In the present study the dynamic changes of the intestinal microbiome are observed over a 4-week period in the different stages of the menstrual cycle in women at childbearing age. The focus is on how the dynamic changes of sex hormones during a menstrual cycle of women at childbearing age (with or without contraception) are related to microbiological colonization of the gut. In Addition the Expression of the β-glucuronidase by the bacteria will be investigated.

Detailed description: Our gut has a complex and diverse bacterial population which is called the microbiome. The number of bacteria in the intestine is estimated to exceed 10\^14. The composition of the microbiome is individual and changes over the lifetime of the host.

The composition of a healthy microbiome consists more than 90% of bacteria from the Bacteroidetes and Firmicutes phyla types. Nevertheless the microbiome varies even between healthy individuals and evolves over the lifetime.

Most of the microorganisms are not pathogen, thus they have been shown to interact with several physiological processes in our body. In Addition it has been shown that the bacterial population has an impact on building our gut epithelial cells, our immunology and the defence against pathogens.

Interestingly estrogen and the microbiome seem to be under reciprocal influence. In our body estrogen is only active in the deconjugated form. Therefore, after it was conjugated in the liver, the bacteria in the gut can perform a deconjugation through the secretion of the enzyme ß-glucuronidase. Ultimately, the activated estrogen is going back into blood circulation, otherwise it would leave the body through bile excretion. The composition of the microbiome is fundamental, because the presence and abundance of different gene expressions varies between the different types of bacteria. The bacterial genes which are responsible for metabolizing estrogens are called the estrobolome. However, data whether there is a relationship of the changes of the sex hormones during the menstrual cycle and the intestinal microbiome in women is sparse.

Parts of the estrogens circulating in the body are metabolised in the liver and are then secreted to the intestine conjugated with glucuronide. The intestinal microbiota could potentially affect estrogen metabolism via Beta-glucuronidase activity. Beta-glucuronidase is an enzyme that catalyses the deconjugation of estrogen. As a consequence, it may bind to estrogen receptors and unfold its downstream effects.

Eligibility criteria: Inclusion Criteria:

* women at childbearing age
* age 18-40 years
* BMI 18.5-24.9 kg/m²
* taking oral contraceptives
* not having any contraceptives

Exclusion Criteria:

* chronic and acute infectious diseases
* history of taking antibiotics or probiotics in the last 3 months
* gastrointestinal disorders in the last 3 months
* Polycystic Ovary Syndrome
* disorders of the menstrual cycle (e.g. oligomenorrhea, anovulation)
* other than mediterranean diet

Primary outcomes:
measure: Changes of the B-Glucuronidase, expressed by the intestinal microbiome, during the menstrual cycle in women at childbearing age
timeFrame: Up to 7 weeks
Secondary outcomes:
measure: Changes of the Beta-Glucuronidase during the menstrual cycle in women with oral contraception
timeFrame: Up to 7 weeks
measure: Changes of the Beta-Glucuronidase during the menstrual cycle in women without any contraception
timeFrame: Up to 7 weeks
measure: Changes of the intestinal microbiome during the menstrual cycle in women at childbearing age with- and without contraception
timeFrame: Up to 7 weeks
measure: Relationship of the β-Glucuronidase with the changes of the female sex hormones during the menstrual cycle in women at childbearing age.
timeFrame: Up to 7 weeks
measure: Relationship of the intestinal microbiome with the changes of the female sex hormones during the menstrual cycle in women at childbearing age.
timeFrame: Up to 7 weeks
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
affiliation: Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Unit of Gender Medicine, Medical University of Vienna
name: Alexandra Kautzky-Willer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: