The Effect of Oral Contraceptive Onset on Emotion Regulation in Adolescence

Growing evidence into the effects of the oral contraceptive pill (*the pill*)
points to negative effects on mental health in pill users. Moreover, adolescent
users appear to be most susceptible to pill-related mood and anxiety problems,
these effects are possibly long-term due to the role of sex hormones in brain
development. However, there is a surprising lack of research focusing on this
high risk group and mechanisms behind the effect of the pill on depress ion and
anxiety are still unknown.
Emotion regulation is an important mechanism in maintaining mental
health, is associated with anxiety and depression and has an underlying neural
network that is sensitivity to the hormones administered by the pill; estradiol
and progesterone. Hence, this study will be the first to research whether
starting pill use in adolescents leads to negative effects on emotion
regulation on the level of neural, physiological and psychological processes.
The findings will give insight into the effects of the pill on processes
underlying mental health in new pill users. The current study will lead to
progress of a scientific field which is still in its infancy. Additionally, the
knowledge gained by this research is in line with the recently updated
contraceptive directive from the Nederlands Huisartsen Genootschap (NHG) to
inform contraceptive users about the psychological effects, and could
contribute to improved communication between general practitioner and possible
contraceptive user.

The primary objective is to research whether the oral contraceptive pill in
adolescents has a negative effect on emotion regulation in the form of fear
acquisition and extinction. The secondary objective is to research whether a
disruptive effect of pill use in adolescents is also evident in other forms and
levels of emotion regulation, such as neural changes, emotion reactivity and
regulation ability, physiological and psychological stress regulation, anxiety
and depressive symptoms and mood fluctuations. Additionally, the influence of
sex hormones, puberty phase, premenstrual symptoms, contraceptive-related
side-effects and reason for pill use on the link between pill use and emotion
regulation and mood will be researched.

The study comprises a between-subject design with within-subject measures in
which the study is split into experiments into emotion regulation and
experiments into stress effects. One group of adolescents that has requested a
pill subscription from their GP on their own, will be asked to undergo a pre-
and post-measurement around their first pill use for either the emotion
regulation experiments or stress experiments. The tasks for the study are split
into two separate experiments to reduce the burden on participants while
simultaneously increasing feasibility of the study. Lab visits will take place
just before the first pill intake and three months after pill onset. The
control group consists of adolescents who haven't yet planned to start a
hormonal contraceptive.

The time costs consist of two lab visits of either 2:15 hours for the emotion
regulation experiments and 1:45 hours for the stress experiments, and filling
in a weekly short questionnaire (two minutes) during three months. Within the 4
test hours participants will fill in questionnaires, complete behavioral tasks
and saliva and hair samples will be taken. During behavioral tasks an aversive
scream and pictures with a negative emotional context will be presented during
the emotion regulation experiments. During the stress experiments an unexpected
task will be used to elicit short-term stress and anxiety. Questionnaires will
be administered about mood, demographics, drugs and alcohol use, youth trauma,
partner status, puberty phase, premenstrual symptoms , contraceptive-related
side-effects and reason for pill use. In addition, saliva and hair samples will
be collected for hormone measurements. The risks of the study are negligible.
The time costs of the study is limited (and as a result increases feasibility)
by splitting the study into the separate emotionregulation and stress
experiments. The biggest burden of the study concerns the aversive stimuli
(noise, negative images) and the induced stress. These aversive stimuli are
necessary to measure the different facets of emotion regulation that can be
influenced by hormones: behavioral, experiential, physiological and neural.
The strain on participants will be minimalized by limiting the emotional
discomfort to the experimental setting and limiting the frequency and time of
the stimuli presentation. The participants will be explicitly asked whether
they want to continue participation after practice rounds. There is no risk of
long-term negative effects related to the study, since the stimuli have been
used in previous validated and common experiments that are also administered to
adolescents. The scientific and societal relevance of this study outweighs the
minimal burden. This will be the first study that researches a causal effect of
the pill on different forms and levels of emotion regulation to elucidate the
mechanisms by which the pill increases vulnerability to anxiety and depression
in girls. The elegance of the proposed study design lies in the absence of an
active intervention, in which participants will be followed during their
self-chosen start of the contraceptive pill. The research is group restricted
since the brain of adolescents is very sensitive to sex hormones and it is
likely that the effects of the pill manifest differently than in adult users.
Accordingly, previous research suggests that adolescents have an increased and
possible long term sensitivity to the negative effects of the pill. In
addition, there is a lack of within-sub ject research that focuses on wamen
younger than 18 years old. There is a benefit for the group since the outcomes
of the study could result in potential pill users and prescribers making a
better informed decision around starting pill use during adolescence. The
results could also indicate that a follow-up for psychological side effects
after starting the pill is especially relevant for adolescents and possibly
requires offering alternative contraceptive options. Besides the focus of this
study on clinically relevant changes in mood, researching the effects on
emotion regulation makes it possible to identify a more subtle risk on anxiety
and mood disorders at a later age for this group of contraceptive users.