In the time since I last read and wrote on hormonal contraception, particularly for adolescents, there has been an explosion of research on the effects of exogenous hormones on the immature brain. I last wrote on this topic fourteen years ago, across two blog posts, and while I conducted focus groups and even had a paper near-ready to submit for publication, I never went through with it because of the ways in which any critique of hormonal contraception as a technology gets read as a critique of reproductive autonomy.

That is, I didn’t know if I was ready to write about the topic with enough nuance to avoid my work being misrepresented.

Let’s give it a try today. We’ll consider whether finding differences is always bad, why we need to consider the stronger effects of exogenous synthetic hormones, and why, if these differences are concerning, our concern should focus on younger adolescents.

Getting organized

Something those of us who study hormones often talk about are the organizational versus activational effects of sex steroid hormones on the tissues and organs of the body. While in recent years this distinction has been shown to be simplistic (and most importantly, reversible/malleable!), it’s not a bad framing for an introductory explanation of how bodies develop and respond to hormones. Organizational effects refer to those effects of hormones that differentiate – particularly in terms of how we think about sex variation. So a bolus of estrogen versus a bolus of testosterone is going to organize tissues differently. Activational effects refer to those that rest on the foundation of those organizational effects. This is where hormonal exposures might bring a tissue to expression, as with puberty.

Originally, organizational effects were thought to be early – in utero and the early prenatal period. But the pubertal transition is one of several places scientists are realizing that hormones can still have organizing (or really, re-organizing) influences, producing differentiated effects on tissues based on their exposures.

Enter hormonal contraception. When young people, whose brains are in a critical period where they are responding to and being organized by hormonal exposures, are prescribed hormonal contraception, they are replacing whatever hormonal exposures come from their endogenous (from within) hormones with an exogenous (from without) one. Exogenous, synthetic hormones may have a greater binding affinity – this means they can exert stronger effects via hormone receptors.

For a full-grown person not in a critical transition period, this may not matter. For a young person whose hormonal exposures are more variable (because of typical experiences of infrequent menstrual cycles, lower hormone concentrations, and anovulation) this could lead to significant differences in terms of how their tissues and organs differentiate and learn to respond to hormones.

Two big points to make here: First, there are many reasons a young person (and their caregiver) may be considering a hormonal treatment at this age: dysmenorrhea (painful periods) are very common, they may already be developing endometriosis, they may need a less easy-to-spot form of contraception, they may have premenstrual dysphoric disorder, they may be non-binary or trans – and a hundred other possibilities. Some of these are very, very important for quality of life, some are suicide prevention. There are a lot of phenomena out there where a hormonal treatment is the only feasible option, and the alternative is terrible.

Second, we need not fear change. That is, many, many factors influence our endogenous hormones and therefore also have reorganizing effects on the adolescent brain, from exercise to schooling to pandemics to authoritarian regimes to family separation to climate change to inciting joy. And so, we need not fear hormonal treatments simply because they influence the brain in some way. What we need to ask is, under certain circumstances and for certain bodies, are these treatment exposures influencing the brain in a way that increases the risk of downstream harm?

We also need to ask, how long does the reorganization period tend to last? One recent review paper using an animal model shows that puberty is a crucial time for brain reorganization, with evidence of pruning of the synapses (this is what transmits electronic nerve impulses), dendrites (cytoplasmic processes that extend from neurons; what the axon signals to), and dendritic spines (additional protrusions from dendrites).¹ A host of papers looking at the same dataset of 297 14-24 year olds finds something similar: the adolescent period is a time for both pruning and consolidation of brain connections.^2,3 When I try to look further back into childhood, I find 10-14 seems to be an especially important window, and then secondarily the 14-17 or even 19 window – but it depends on what’s being studied.^3–5

I am very much a non-expert here, but from my reading of these articles, it stands to reason that the most sensitive period for impacting adolescent brain reorganization is on the earlier end – closer to puberty itself. This suggests – again, to me as a non-expert – that it’s not all of adolescence (which some could rightly argue starts at puberty but brings us into the early twenties) that requires our attention, but really the first third to half of that period.

Hormonal contraceptives and the brain: impacts on fear dysregulation

There may be times the effects of exogenous hormones create organizational changes that are unwanted. Fear dysregulation (the dysregulation of processes like fear acquisition and fear extinction – so basically the inability to appropriately and adaptively respond to a fear-based stressor)⁶ is a risk factor for post-traumatic stress disorder and anxiety disorder, two phenomena for which girls are at higher risk than boys, and peak onset is in adolescence.⁷ Therefore we should care very much about the kinds of factors that might produce variation in, or increase the risk of, dysregulation of fear processes as seen by known structural changes in the brain.

In a recent study comparing structural brain MRIs of ninety-eight adults, sixty-one current users of hormonal contraceptives to thirty-seven past users, researchers found that an earlier age of onset of hormonal contraception (in the range of 14-15 years of age) corresponded to structural changes in parts of the brain related to fear circuitry and emotional regulation.⁷

Several animal studies have had similar findings relating more to longer duration of OC use, exploring different mechanisms relating to the hormone exposures themselves. In one study, levonorgestrel only (this is a progestin, and often found in the progestin-only pill and the hormonal IUD) impaired fear extinction where more of a combo pill formulation (ethinyl estradiol plus levonorgestrel) did not. These effects were found even though the tests were run after the rats were no longer being exposed to the synthetic hormones.⁸ Another study found that hormonal contraceptives (ethinyl estradiol and levonorgestrel again) impacted risk-assessment behaviors and anxiety-like behavior.⁹

To prescribe or not to prescribe

I am not a medical doctor and I don’t dispense medical advice. What I simply wish, when it comes to hormonal contraception in particular, is that we had greater knowledge about both the “pro” and “con” columns so that patients and caregivers can make informed choices.

The last decade or so of research on the organizational effects of hormonal contraception on the adolescent brain has only barely started to answer whether the effects being observed are worrisome and belong in the “con” column. Given the wide variety of hormonal preparations, the smaller sample size when it comes to younger participants, and the limitations on what has been measured so far, there is far more work to be done – work nearly impossible in this political climate.

What I conclude from my reading thus far – and I’m always willing to have my opinion changed – is that there are greater effects of hormonal contraception on younger brains than older brains, and that this should be part of what we think about when we decide whether it is the right treatment for a young person, especially those fifteen and under.

References

1.          Juraska, J. M. & Drzewiecki, C. M. Cortical reorganization during adolescence: What the rat can tell us about the cellular basis. Developmental Cognitive Neuroscience 45, 100857 (2020).

2.          Váša, F. et al. Adolescent Tuning of Association Cortex in Human Structural Brain Networks. Cereb Cortex 28, 281–294 (2018).

3.          Whitaker, K. J. et al. Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome. Proceedings of the National Academy of Sciences of the United States of America 113, 9105–9110 (2016).

4.          Feinberg, I. & Campbell, I. G. Sleep EEG changes during adolescence: An index of a fundamental brain reorganization. Brain and Cognition 72, 56–65 (2010).

5.          Romeo, R. D. The impact of stress on the structure of the adolescent brain: Implications for adolescent mental health. Brain Research 1654, 185–191 (2017).

6.          Iqbal, J., Huang, G.-D., Xue, Y.-X., Yang, M. & Jia, X.-J. The neural circuits and molecular mechanisms underlying fear dysregulation in posttraumatic stress disorder. Frontiers in neuroscience 17, 1281401 (2023).

7.          Brouillard, A., Davignon, L-m., Vachon-Presseau, E., Roy, M., & Marin M.-F. Starting the pill during adolescence: Age of onset and duration of use influence morphology of the hippocampus and ventromedial prefrontal cortex. European Journal of Neuroscience 60(8), 5876–5899 (2024).

8.          Brooke, M. & Graham, B. M. Birth controlling your fears: The long-term effects of adolescent exposure to hormonal contraceptives on fear extinction in long-evans female rats. Hormones and Behavior 174, 105789 (2025).

9.          Gilfarb, R. A. et al. Hormonal contraceptives during adolescence impact the female brain and behavior in a rat model. Hormones and Behavior 171, 105725 (2025).