The Pill Project - Oral Contraceptive and Serotonergic Brain Signaling

• Status: Recruiting
• Trial end date: 2025-08-31
• Target enrollment: 0
• Participant gender: Female

Summary

Large register based work has shown that starting on oral contraceptives (OCs) is associated with an increased risk of developing depressive episodes. It is not known why this is, but changes in the serotonergic brain system might play a role. Intriguingly, in cross-sectional work, the investigators have demonstrated a lower level of the serotonin 4 receptor globally in the brain of healthy women using oral contraceptives compared to non-users. The order of magnitude of this difference is comparable to what has been observed in depressed individuals relative to healthy controls. In this study, the investigators will apply a longitudinal design to determine if starting on oral contraceptives induces a reduction in the serotonin 4 receptor in healthy women and whether such changes are related to potential changes in measures of cognition as well as mood/affect and sexual desire.

The study is a single-blind randomized placebo-controlled trial with a 3-month intervention paradigm of either Femicept (2nd generation combined oral contraceptive) or placebo. The investigators will include participants until 20 women have completed the study in each arm. Participants will go through an investigational program, including PET and MR brain scans and neuropsychological testing, before starting on the treatment and again during the third pill cycle. To capture changes in mood/ and sexual desire, the participants will complete daily questionnaires during the baseline menstrual cycle and during third pill cycle.

A linear latent variable model will be used to evaluate if OC use induces changes in the serotonin 4 receptor level and such changes will be correlated to changes in secondary outcomes (i.e., cognitive and psychometric measures).

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Rigshospitalet, Denmark
• Treatments: Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined

Criteria

Inclusion Criteria:

• Healthy women at 18-22 years of age

• No use of hormonal contraception within the last year

• Having a regular menstrual cycle of approximately 28 days, i.e., approximately 28 days between first day of menstrual bleedings.

Exclusion Criteria:

• Current or previous neurological or psychiatric disease, severe somatic disease, or consumption of medical drugs likely to influence the test results

• Non-fluent in Danish or pronounced visual or auditory impairments

• Current or past learning disability

• Current or previous pregnancy

• A wish to become pregnant within the following 6 months

• Participation in experiments with exposure to radioactivity (> 10 mSv) within the last year or significant occupational exposure to radioactivity

• Contraindications for MRI (pacemaker, metal implants, claustrophobia)

• Allergy to the ingredients in the administered drug

• A diagnosis of hypo- or hypertension

• A history of head injury or concussion resulting in loss of consciousness for more than 2 min

• Alcohol abuse

• Drug use other than tobacco and alcohol within the last 30 days

• Cannabis > 50 x lifetime

• Recreational drugs > 10 x lifetime (for each substance)

• Nicotine addiction

• Current psychoactive medication

• Any risk factors for thromboembolic events

• Other contraindications for use of Femicept