Stress Reactivity and Hormonal Contraception


University Hospital Tuebingen




Hormonal Contraception


Other: Combined oral contraception
Other: Discontinuation of a combined oral contraception

Study type


Funder types




Details and patient eligibility


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.

Full 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.


75 estimated patients




18 to 40 years old


Accepts Healthy Volunteers

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Trial design

75 participants in 3 patient groups

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

Trial contacts and locations



Central trial contact

Nils B. Kroemer, Professor; Melanie Henes, PD

Data sourced from

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