Hormonal Contraceptive Effects on Mental Health and Brain Function

Hormonal contraceptives, widely used by women of reproductive age, exert systemic influences beyond birth control, extending to mood regulation, cognitive processing and neural architecture. Synthetic oestrogens and progestins can interact with neurotransmitter systems implicated in stress, reward and emotion recognition. While many users tolerate these medications without significant psychological effects, a subset report alterations in mood, changes in stress responsivity and subtle modifications of cognitive performance. Neuroimaging and physiological studies indicate that exogenous hormones may mimic chronic stress signals in the hypothalamic–pituitary–adrenal axis, influence grey matter volumes in limbic regions and modulate executive functions. Understanding these effects is critical to inform individualised contraceptive choices and to guide future development of formulations with optimised neuropsychiatric tolerability.

Research from Nature Portfolio

An integrative physiological study found that women using oral contraceptives display elevated circulating cortisol, altered lipid metabolites and enhanced glucocorticoid receptor signalling, akin to chronic stress exposure, alongside reduced hippocampal volume. Genetic variation in a stress-related gene further modulates these changes, suggesting individual vulnerability. Building on structural imaging, a subsequent investigation reported that the cumulative duration of past contraceptive use correlates positively with grey matter volumes in the hippocampus and basal ganglia, with hippocampal changes reversing after a period comparable to treatment length. These findings collectively highlight long-term and potentially partially reversible effects of synthetic steroid exposure on stress circuits and brain morphology.

Hormonal Contraceptive Effects on Mental Health and Brain Function publication trend

The graph below shows the total number of articles in hormonal contraceptive effects on mental health and brain function across all publications each year (not limited to Nature Index journals).

Technical terms

HPA axis: Hypothalamic–pituitary–adrenal axis, the body’s central stress response system.

Glucocorticoid signalling: Cellular pathways activated by cortisol and related steroid hormones.

Grey matter volume: The measured size of neuron-rich brain tissue, often assessed by structural MRI.

Executive functions: Higher-order cognitive processes including inhibition, working memory updating and task switching.

Functional neuroimaging: Techniques such as fMRI that visualise brain activity in response to tasks or stimuli.

References

1. Effects of Hormonal Contraceptives on Mood: A Focus on Emotion Recognition and Reactivity, Reward Processing, and Stress Response. Current Psychiatry Reports (2019).
2. Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives. Scientific Reports (2017).
3. Previous contraceptive treatment relates to grey matter volumes in the hippocampus and basal ganglia. Scientific Reports (2019).
4. Symptoms of mental disorders and oral contraception use: A systematic review and meta-analysis. Frontiers in Neuroendocrinology (2023).
5. The Relationship Between the Menstrual Cycle, Oral Contraceptives, and Executive Function – Inhibition, Updating, and Shifting. European Psychologist (2023).
6. The Effects of Hormonal Contraceptives on the Brain: A Systematic Review of Neuroimaging Studies. Frontiers in Psychology (2020).