This Is Your Brain on Contraceptives (2025)

Over 300 million women globally use hormonal contraceptives (HC). Eighty-two percent of American women of reproductive age have used HCs at some point in their lives. Studying their effects on neurobiology is complicated by the fact that there are over 100 different formulations of HCs containing either a synthetic progestin only or a synthetic progestin in combination with a synthetic estrogen. Currently, relatively little is known about the impact of HCs on the brain. This is surprising, and frankly disappointing, given that these preparations have been used for over eighty years, and the nervous system is a major target for the actions of these hormones. This is what is currently known.

Evidence from neuroimaging studies

These neuroimaging studies explored the structural changes that occur during HC use compared with the natural menstrual cycle. The results are nuanced. Neuroimaging studies have revealed both increases and decreases in volume and cortical thickness of various cortical and subcortical brain regions. These changes are fairly consistent and significant and occur in areas that mediate the generation of emotions and cognitive processing.

The cortical volumes in women using HCs, as compared to women naturally cycling, were decreased throughout the frontal lobe as well as some subcortical regions that control movement and memory consolidation. In contrast, increases in cortical volumes were seen throughout the parietal, occipital and temporal lobes. The cortex was thinner in the left anterior and posterior cingulate gyrus and the left insula. The cingulate and insula play important roles in emotional control and processing of sensory information related to emotions. (To learn more about the function of these brain regions, go here) The behavioral consequences of structural alterations in these specific brain regions have not been determined.

It is important to recognize that observing these structural changes induced by HC falls short of understanding the neurobiological mechanisms that produced these changes. These cortical areas might be thinner or smaller due to the presence of fewer neurons, or fewer synapses or variations in vascular size or water content. Fortunately, animal models have provided some insights into what might be causing these structural changes.

Studies using animal models

Healthy intact (with active ovaries) female rodents given ethinyl estradiol and the progestin levonorgestrel show significant changes in various neurotransmitter systems, including reduced dopamine cell number and dopamine levels in the nigrostriatal system; this is like what is seen in the brains of Parkinson’s patients. Like humans given HCs, rodents show significant structural and biochemical changes within the hippocampus. The hippocampus is a key brain region that is critically involved in consolidating memories; dysfunction there leads to conditions like major depressive disorder and Alzheimer’s disease. Normal hippocampal function is controlled by gonadal hormones such as estrogens, progesterone, and androgens as well as by 17β-estradiol. These hormones usually support spatial memory, synaptic plasticity, and neurogenesis. Exposure to even slightly high levels of these hormones impaired spatial memory. The cognitive impairments might be due to decreased production of brain-derived neurotrophic factor (BDNF) which is also influenced by these hormones and plays a crucial role in learning and memory processes. Hormone treatment also altered neurogenesis in this brain region, which is known to be dependent on BDNF levels.

Hormones during adolescence

Age at first use is an important factor to consider when investigating the effects of HCs on the brain. In the United States, HCs are approved for use after menarche. One in four adolescent females will be exposed to HCs by age 18. Unfortunately, the adolescent brain may be uniquely sensitive to the effects of HCs. Studies suggest that HC use among adolescents enhances the risk for major depression even years later after hormone treatment is discontinued. Adolescents who use HCs are more likely to be prescribed antidepressants as adults and are at greater risk of suicide. The suppression of endogenous hormones and/or the introduction of exogenous synthetic hormones during adolescence have the potential to impact hormone-mediated neurodevelopmental processes.

The extent to which HCs alter the development of the adolescent brain, or the structure of the adult brain, and whether these changes are permanent remains to be determined by future studies. The effects of contraceptive hormone use are only now being studied adequately.

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