OSU Probes Birth Control’s Effects on Adolescent Prefrontal Cortex

Researchers at Ohio State University (OSU) have linked the synthetic hormones found in birth control pills, patches, and injections with disordered signal transmission between cells in the prefrontal cortex, an area of the brain that continues to develop throughout adolescence. When compared to control rats, animals receiving hormonal contraceptives also produced higher levels of the stress hormone corticosterone, which is similar to cortisol in humans.

An estimated 2 in 5 teenage girls in the United States have sexual intercourse between age 15 and 19, and the vast majority use a contraceptive. Of those using birth control, almost 5% use hormonal contraceptives, also known as long-acting reversible contraceptives. These products are also prescribed to treat acne and heavy periods. 

While reproductive health experts consider hormonal contraceptives good choices for adolescents because they’re safe and highly effective at preventing pregnancy, how they might affect the developing brain has gone relatively unstudied.

The OSU work, which appears as a poster presentation at Neuroscience 2022, focused on the prefrontal cortex, a region where mood is regulated, because previous research associated early adolescent use of hormonal contraceptives with risk for depression in adulthood.

The researchers gave a combination of synthetic estrogen and progesterone typically found in hormonal contraceptives to female rats for three weeks beginning about a month after they were born, an age equivalent to early adolescence in humans. Researchers confirmed the drugs disrupted the animals’ reproductive cycling; these birth control products work by stopping ovaries from producing hormones at levels necessary to generate eggs and making the uterine lining inhospitable for an egg to implant.

Blood samples showed the treated rats were producing more corticosterone than untreated animals, a sign that they were stressed. And after being subjected to and recovering from an experimental stressor, the treated rats’ corticosterone level remained high. Their adrenal glands were also larger, suggesting their stress hormone production was consistently higher than that of control animals.

An analysis of gene activation markers in the animals’ prefrontal cortex showed a decrease in excitatory synapses in that region of treated rats’ brains compared to controls, but no change to inhibitory synapses, a phenomenon that could set up an imbalance of normal signaling patterns and result in altered behavior. The loss of only excitatory synapses in the prefrontal cortex has been linked to exposure to chronic stress and depression in previous research.

“What this means for the function of particular circuits, we don’t know yet. But this gives us a clue of where to look next in terms of what the functional outcomes might be,” says co-author Kathryn Lenz, associate professor of psychology at OSU.

The researchers hope their findings help in weighing the risks and benefits of reproductive health choices. “Birth control has had a major positive impact for women’s health and autonomy—so it’s not that we’re suggesting adolescents should not take hormonal contraceptives,” says senior study author Benedetta Leuner, associate professor of psychology at OSU. “What we need is to be informed about what synthetic hormones are doing in the brain so we can make informed decisions—and if there are any risks, then that’s something that needs to be monitored. Then if you decide to use hormonal birth control, you would pay more attention to warning signs if you knew of any possible mood-related side effects.”