Hormonal ContraceptionNCT06223126
Stress Reactivity and Hormonal Contraception
An observational study of Hormonal Contraception, run by University Hospital Tuebingen at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hormonal Contraception
- What is being tested?
- Combined oral contraception and Discontinuation of a combined oral contraception
- Type of treatment
- Pill or oral medicine
- How many people
- 75 participants
- Where
- 1 siteGermany
- Study dates
- 22 Jan 2024to Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: community sample
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Psychiatry & Psychotherapy, University of Tübingen
Tübingen, Baden-Wurttemberg, 72076
About this study
Official title: Effects of Oral Contraceptive on Stress Reactivity and Mood Homeostasis
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.
Read the detailed description
The study will use a longitudinal design with two time points to compare three groups, the women who want to start taking the pill, the women who want to stop taking it, and those who are long-term users of the pill. They will be exposed to a psychosocial stress induction task (Montreal Imaging Stress Task; MIST) in functional magnetic resonance imaging (fMRI) to get mechanistic insights. Measurements will be done before and during OC use (group 1; OC-Starters) and during and after the termination of OC use (group 2; OC-Stoppers). Therefore, at the first time point (T1) of the measurements, the OC-Starter will be in their early follicular phase while the OC-Stopper will be in their active pill intake weeks. At the second time point (T2), the OC-Starter will be in the active pill intake weeks and the OC-Stopper in their early follicular phase. The OC-Long-Term users (group 3) will be in their active pill intake weeks at both measurement time points (T1 and T2). Along with measuring heart rate, skin conductance and pulse oximetry as indicators of stress, saliva samples will be collected during the assessment in the fMRI to determine cortisol levels. Hormones (e.g., estradiol, ethinylestradiol, testosterone, and their precursor steroids and metabolites) will be assessed from blood samples at both time points (T1 and T2). Hair samples are collected at both measurement time points (T1 and T2) from the study participant to record the cumulative cortisol secretion of the past 3 months (= 3cm of hair) as a marker for chronic stress. For this purpose, a small strand of hair on the back of the head of the participant will be cut as close to the scalp as possible. These measures will be analyzed alongside individual markers of stress responsivity derived from brain imaging and questionnaires on stress and emotion regulation. These trait-like measures will be assessed at baseline (T1) and three months after the start/end of OC use (T2) to evaluate long-term changes. Additionally, at T1 and T2, medically trained personnel will conduct transvaginal ultrasound examinations to visualize the female reproductive organs and assess any organic changes resulting from OC usage. After the first time point T1, ambulatory assessments will be utilized over three months in all groups to assess daily fluctuations in stress and mood over the transition period starting or stopping OC and to ensure ecological validity of mood and stress reactivity. For this purpose, changes in average mood and mood variations will be quantified by collecting self-reports of daily hassles. A voluntary follow-up questionnaire is then used after six months (T3) to assess long-term changes in mood and stress reactivity.
- Conditions
- Hormonal Contraception
- Being tested
- Combined oral contraception, Discontinuation of a combined oral contraception
- Keywords
- Stress reactivity, Mood homeostasis, fMRI, Oral Contraceptive, Sex hormones, Cortisol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined oral contraceptionOther
Women, who want to start taking birth control pills will get a prescription for oral contraception at the discretion of their own attending physician
Discontinuation of a combined oral contraceptionOther
Cessation of the use of combined oral contraceptives
| Study group | Role | What they receive |
|---|---|---|
| Oral Contraception-Starter | Women who start taking oral contraception Receives: Other: Combined oral contraception | |
| Oral Contraception-Stopper | Women who stop taking oral contraception Receives: Other: Discontinuation of a combined oral contraception | |
| Oral Contraception-Long-Term User | Women who use oral contraception continuously |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Changes in endogenous and synthetic hormone levels will be assessed from blood samples before and after starting vs. stopping oral contraceptive use.
Measured: Pre medication vs. 3 months after medication
Oral Contraceptive induced changes in brain volume (structure)
Changes operationalized with a structural T1 scan of the whole brain before and after starting vs. stopping oral contraceptive use.
Measured: Pre medication vs. 3 months after medication
Oral Contraceptive induced changes in chronic stress
Associations of chronic stress, assessed via hair cortisol measures and chronic stress questionnaire (Trier Inventar of Chronic Stress - TICS; value range = [0 228]; higher outcome relates to a higher chronic stress rating) with oral contraception and stress reactivity. To record the cumulative cortisol secretion of the past 3 months (= 3cm of hair) as a marker for chronic stress, a small strand of hair on the back of the head of the participant will be cut as close to the scalp as possible.
Measured: Pre medication vs. 3 months after medication
Oral Contraceptive induced organic changes in reproductive organs
Changes operationalized with a transvaginal ultrasound to examine the female reproductive organs (uterus, fallopian tubes and ovaries) before and after starting vs. stopping oral contraceptive use.
Measured: Pre medication vs. 3 months after medication
Oral Contraceptive induced long-term changes in mood
Changes in positive and negative mood ratings measured with the PANAS questionnaire (scale 1-5)
Measured: Six months after medication change
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start22 Jan 2024
- Primary completionJul 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hormonal ContraceptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University, German Research Foundation
- Responsible party
- Sponsor
- Investigators
- Nils B. Kroemer, Professor, Principal investigator, Department of Psychiatry & Psychotherapy, University of Tübingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06223126
- Sponsor's protocol ID
- TUE011_IRTG_P03
- Status last verified
- Aug 2023
- First submitted
- 15 Jan 2024
- Last updated
- 1 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After the publication of the key results of the study, all anonymized research data, including imaging data, will be made publicly available (e.g., at openfmri.org).
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Oral Contraceptive on Stress Reactivity and Mood Homeostasis
- ClinicalTrials.gov ID
- NCT06223126
- Acronym / sponsor ID
- TUE011_IRTG_P03
- Conditions
- Hormonal Contraception
- Keywords
- Stress reactivity, Mood homeostasis, fMRI, Oral Contraceptive, Sex hormones, Cortisol
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- Uppsala University, German Research Foundation
- Study start
- 22 Jan 2024 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 25 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study will use a longitudinal design with two time points to compare three groups, the women who want to start taking the pill, the women who want to stop taking it, and those who are long-term users of the pill. They will be exposed to a psychosocial stress induction task (Montreal Imaging Stress Task; MIST) in functional magnetic resonance imaging (fMRI) to get mechanistic insights. Measurements will be done before and during OC use (group 1; OC-Starters) and during and after the termination of OC use (group 2; OC-Stoppers). Therefore, at the first time point (T1) of the measurements, the OC-Starter will be in their early follicular phase while the OC-Stopper will be in their active pill intake weeks. At the second time point (T2), the OC-Starter will be in the active pill intake weeks and the OC-Stopper in their early follicular phase. The OC-Long-Term users (group 3) will be in their active pill intake weeks at both measurement time points (T1 and T2). Along with measuring heart rate, skin conductance and pulse oximetry as indicators of stress, saliva samples will be collected during the assessment in the fMRI to determine cortisol levels. Hormones (e.g., estradiol, ethinylestradiol, testosterone, and their precursor steroids and metabolites) will be assessed from blood samples at both time points (T1 and T2). Hair samples are collected at both measurement time points (T1 and T2) from the study participant to record the cumulative cortisol secretion of the past 3 months (= 3cm of hair) as a marker for chronic stress. For this purpose, a small strand of hair on the back of the head of the participant will be cut as close to the scalp as possible. These measures will be analyzed alongside individual markers of stress responsivity derived from brain imaging and questionnaires on stress and emotion regulation. These trait-like measures will be assessed at baseline (T1) and three months after the start/end of OC use (T2) to evaluate long-term changes. Additionally, at T1 and T2, medically trained personnel will conduct transvaginal ultrasound examinations to visualize the female reproductive organs and assess any organic changes resulting from OC usage. After the first time point T1, ambulatory assessments will be utilized over three months in all groups to assess daily fluctuations in stress and mood over the transition period starting or stopping OC and to ensure ecological validity of mood and stress reactivity. For this purpose, changes in average mood and mood variations will be quantified by collecting self-reports of daily hassles. A voluntary follow-up questionnaire is then used after six months (T3) to assess long-term changes in mood and stress reactivity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Oral Contraception-Starter | – | Other: Combined oral contraceptionWomen who start taking oral contraception |
| Oral Contraception-Stopper | – | Other: Discontinuation of a combined oral contraceptionWomen who stop taking oral contraception |
| Oral Contraception-Long-Term User | – | –Women who use oral contraception continuously |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- community sample
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combined oral contraceptionWomen, who want to start taking birth control pills will get a prescription for oral contraception at the discretion of their own attending physician | Other | Oral Contraception-Starter |
| Discontinuation of a combined oral contraceptionCessation of the use of combined oral contraceptives | Other | Oral Contraception-Stopper |
Primary outcome
Stress-induced changes in mood
Time frame: Pre medication vs. 3 months after medication
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.
Stress-induced changes in the subjective experience of stress
Time frame: Pre medication vs. 3 months after medication
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.
Stress-induced changes in brain response
Time frame: Pre medication vs. 3 months after medication
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.
Stress-induced changes in functional connectivity
Time frame: Pre medication vs. 3 months after medication
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.
Stress-induced changes in skin conductance
Time frame: Pre medication vs. 3 months after medication
Skin conductance [μS] during stress condition vs. no stress condition as indicators of stress during fMRI
Stress-induced changes in pulse
Time frame: Pre medication vs. 3 months after medication
Pulse oximetry during stress condition vs. no stress condition as indicators of stress during fMRI
Stress-induced changes in cortisol
Time frame: Pre medication vs. 3 months after medication
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.
Oral Contraceptive induced changes in average mood during transition phase
Time frame: Over the course of three months regularly (30 times in total), about 5 minutes per day
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.
5 secondary outcomes
Oral Contraceptive induced changes in hormone levels
Time frame: Pre medication vs. 3 months after medication
Oral Contraceptive induced changes in brain volume (structure)
Time frame: Pre medication vs. 3 months after medication
Oral Contraceptive induced changes in chronic stress
Time frame: Pre medication vs. 3 months after medication
Oral Contraceptive induced organic changes in reproductive organs
Time frame: Pre medication vs. 3 months after medication
Oral Contraceptive induced long-term changes in mood
Time frame: Six months after medication change
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
- Individual participant dataSharing planned: Yes. After the publication of the key results of the study, all anonymized research data, including imaging data, will be made publicly available (e.g., at openfmri.org).
Related trials for Hormonal Contraception
Not yet recruiting
Safety of a Contraceptive Copper Vaginal Ring
Contraception, Birth Control
Recruiting
The Influence of Plan B® on Cardiovascular Health.
Female, Premenopausal
Recruiting
Contraceptive Efficacy Study of Ovaprene
Contraception
Active, not recruitingObservational study
Cardiovascular Impact of the Menstrual Cycle and Contraception - Longitudinal Evaluation
Women Under Hormonal Contraception (Pill) or Without Hormonal Contraception
RecruitingPhase 4
Adaptions and Resiliency to Multi-Stressor OpeRations
Musculoskeletal Injury, Hypogonadism
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nils B. Kroemer, Professor principal investigator
Department of Psychiatry & Psychotherapy, University of Tübingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hormonal Contraception, run by University Hospital Tuebingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stress-induced changes in mood (time frame: Pre medication vs. 3 months after medication). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2024.