Assessing the role of adolescent hormonal contraceptive use on risk for depression: a 3-year longitudinal study protocol

Bita Zareian,Colin J Ross,Frances S Chen,Jason D Rights,Sabrina Ge,Liisa A M Galea,Annie C Hayward,Christine Anderl,Jerilynn C Prior,Joelle Lemoult

doi:10.1186/s12905-022-01623-2

Abstract

BackgroundThe incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females’ risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning.MethodsUsing a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be assessed at three time points: once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels.DiscussionIn this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.

Highlights

The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone
We examine whether and how introducing a supra-physiological dose of synthetic estrogens and approximately physiological dose of progestin derivatives through the use of combined hormonal contraceptives (CHC), affects female adolescents’ risk for developing depressive symptoms, as well as their risk for receiving a diagnosis of major depressive disorder (MDD)
Covariates and control variables We will assess all confounds that, to our knowledge, have previously been found or proposed to at least partially account for the observed relationship between CHC use and depression, so that they can be accounted for in our analyses

Summary

Introduction

The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may contribute to the increased occurrence of depression in females that begins in early adolescence. We examine whether and how introducing a supra-physiological dose of synthetic estrogens and approximately physiological dose of progestin derivatives through the use of combined hormonal contraceptives (CHC), affects female adolescents’ risk for developing depressive symptoms, as well as their risk for receiving a diagnosis of major depressive disorder (MDD). We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning, and the possible mediating effects of stress responses and social-emotional functioning in the association between CHC use and depression

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