Stress Reactivity and Hormonal Contraception

NCT06223126 | Unknown

• 1 other identifier: TUE011_IRTG_P03
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

For almost 60 years, millions of women globally have relied on oral contraceptive (OC) pills for pregnancy prevention and addressing menstrual irregularities. However, 4-10% of users experience mood-related side effects such as depression and anxiety, often leading to discontinuation of OC use. Previous studies also indicate that OC usage may lead to chronic alterations in brain structure and the regulation of the hypothalamic-pituitary-adrenal axis, a system involved in regulating stress responses. In the proposed study the investigators aim to investigate in more detail how women who start taking oral contraception (OC) and women who stop taking OC differ in their stress reactivity and their mood from long-term OC users. Furthermore, assessing hormones will help to shed light on the connection between OC, stress reaction, sex hormones and the brain. To achieve this, individual biomarkers will be evaluated, including changes in brain anatomy, functional responses and connectivity during acute psychosocial stress and early changes in mood and well-being through ambulatory assessment.

Conditions

Hormonal Contraception

Keywords

Stress reactivity; Mood homeostasis; fMRI; Oral Contraceptive; Sex hormones; Cortisol

Outcome Measures

Primary Outcomes (8)

• Stress-induced changes in mood

  Change in mood after stress inductions measured by ratings of positive and negative affect before and after the stress task will be measured with the PANAS questionnaire (scale 1-5). It will be measured twice three months apart; each time: 60min before stress onset, just before stress onset, immediately after stress, 40min after stress onset, 60min after stress onset, 90min after stress onset.

  Pre medication vs. 3 months after medication

• Stress-induced changes in the subjective experience of stress

  Change in subjective stress experience after stress inductions measured by stress items before and after the stress task will be measured with a visual analog scale (1-10). It will be measured twice three months apart; each time: 60min before stress onset, just before stress onset, immediately after stress, 40min after stress onset, 60min after stress onset, 90min after stress onset.

  Pre medication vs. 3 months after medication

• Stress-induced changes in brain response

  BOLD response to stress (changes in amplitude) within regions associated with stress reactivity and regulation (amygdala, hippocampus, prefrontal cortex, anterior cingulate cortex (ACC), middle frontal gyrus (MFG), right superior temporal gyrus (STG), insula, striatum, and praecuneus) will be quantified using fMRI to assess differences between stress vs. control conditions during the stress task.

  Pre medication vs. 3 months after medication

• Stress-induced changes in functional connectivity

  Functional connectivity will be assessed within regions associated with emotional processing (amygdala, hippocampus, prefrontal cortex, hypothalamus, striatum, insula) using fMRI to assess differences between stress vs. control conditions during the stress task.

  Pre medication vs. 3 months after medication

• Stress-induced changes in skin conductance

  Skin conductance \[μS\] during stress condition vs. no stress condition as indicators of stress during fMRI

  Pre medication vs. 3 months after medication

• Stress-induced changes in pulse

  Pulse oximetry during stress condition vs. no stress condition as indicators of stress during fMRI

  Pre medication vs. 3 months after medication

• Stress-induced changes in cortisol

  Salivary cortisol levels to determine cortisol levels \[μg/dL or nmol/L\] during stress condition vs. no stress condition and baseline as indicators of stress/Hypothalamic-Pituitary-Adrenal-axis activation. It will be measured twice three months apart; each time: 60min before stress onset, just before stress onset, immediately after stress, 40min after stress onset, 60min after stress onset, 90min after stress onset.

  Pre medication vs. 3 months after medication

• Oral Contraceptive induced changes in average mood during transition phase

  Changes in positive and negative mood ratings (5 mood and 5 stress items, scale 1-10), measured with ecological momentary assessment after starting vs. stopping oral contraceptive intake.

  Over the course of three months regularly (30 times in total), about 5 minutes per day

Secondary Outcomes (5)

• Oral Contraceptive induced changes in hormone levels

  Pre medication vs. 3 months after medication

• Oral Contraceptive induced changes in brain volume (structure)

  Pre medication vs. 3 months after medication

• Oral Contraceptive induced changes in chronic stress

  Pre medication vs. 3 months after medication

• Oral Contraceptive induced organic changes in reproductive organs

  Pre medication vs. 3 months after medication

• Oral Contraceptive induced long-term changes in mood

  Six months after medication change

Study Arms (3)

Oral Contraception-Starter

Women who start taking oral contraception

Other: Combined oral contraception

Oral Contraception-Stopper

Women who stop taking oral contraception

Other: Discontinuation of a combined oral contraception

Oral Contraception-Long-Term User

Women who use oral contraception continuously

Interventions

Combined oral contraception OTHER

Women, who want to start taking birth control pills will get a prescription for oral contraception at the discretion of their own attending physician

Oral Contraception-Starter

Discontinuation of a combined oral contraception OTHER

Cessation of the use of combined oral contraceptives

Oral Contraception-Stopper

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

community sample

You may qualify if:

• Women, who want to start using oral contraception (no hormonal contraception use for at least 4 months; regular menstrual cycle (between 25 and 35 days) prior to participation)
• Women, who want to stop using oral contraception (OC pill use for at least 6 months; regular intake of OC pill)
• Long-term oral contraception user (OC pill use for at least 6 months; regular intake of OC pill)
• German language fluency
• Normal or corrected vision
• Body-mass index (BMI): 18-35 kg/m2

You may not qualify if:

• Neurological or psychiatric disease
• Medical problems such as hormonal, metabolic, or chronic diseases (e.g., severe hypertension, diabetes, or congestive heart failure)
• Pregnancy, delivery, and lactation (current and within the last year)
• Any kind of steroid hormonal, pharmacological treatment, or psychotropic treatment in the last three months
• Shift work
• Participants engaging in competitive sports
• contraindication for MRI
• People with non-removable metal objects on or in the body
• Tattoos (if not MRI-incompatible according to expert guidelines)
• Pathological hearing or increased sensitivity to loud noises
• Claustrophobia
• Surgery less than three months ago
• Neurological disease or injury
• Moderate or severe head injury
• Intake of antidepressants or neuroleptics

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• Uppsala University: collaborator
• German Research Foundation: collaborator

Study Sites (1)

Department of Psychiatry & Psychotherapy, University of Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood

Study Officials

• Nils B. Kroemer, Professor

  Department of Psychiatry & Psychotherapy, University of Tübingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: January 25, 2024
• Study Start: January 22, 2024
• Primary Completion: July 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 1, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will become available after an embargo period of 12 months after completion of the study
• Access Criteria: Until the data is publicly available, researchers may contact the lead PI to gain access

Locations

DE (1)