I attended a talk called Sex Differences in the Brain by Dr. Jill Goldstein. She discussed the biology of sex, and how hormonal changes in neurodevelopment can have long lasting impacts once out of the womb. Statistically, women are at higher risk of autoimmune disorders, anxiety, or depression, while men are at higher risk of schizophrenia, autism, Parkinson’s, or Alzheimer’s. The talk began with a discussion of the brain, specifically how it is gendered during neurodevelopment. Testosterone is released during the second semester of gestation, which can masculinize the brain and helpe certain traits develop. Estrogen, when released, helps regulate nerve growth and transcription. 

One of the studies discussed was about how drug efficacy can differ by sex. Currently, scientists only test drugs on male animals, not females, on account of the complications of the menstrual cycle, but this in turn means that drugs that are effective on men do not have the same effect on women. Ambien is currently on the only FDA approved drug with sex dependent dosages. The fact remains that women and men absorb, distribute, and metabolize drugs differently based on their sex, and this difference starts in neurodevelopment. Another study looked at the disruption of HPA circuitry in neurodevelopment, and how it increased the chance of cardiovascular disease. When there was extreme stress in the first trimester, males were affected more, but in the second trimester, when sex differences began to emerge, females were affected more, and scientists are still researching why.

The largest study discussed is still ongoing, and followed a prenatal cohort over the course of thirty years, established from 1959-1966. It followed 66,000 pregnancies across seven years, and then continued to follow the adult offspring. Assays included hormone markers, fMRI imaging, cardio exams, immune panels, and strict tracking of the menstrual cycle. It found that women’s brains react differently to stress based on where women were in the cycle. Even if they did not actively feel stressed, the brain would demonstrate markers of stress. Men at all times look like women do in their early follicular cycle, while for women, it varies. This demonstrated something key: that sex differences in the brain do not equate to sex differences in behavior. Further, levels of anti-inflammatory hormones varied based on levels of sex hormones. Deep phenotyping of the mothers further revealed whether their children had depression or not, telling us that in utero exposure to prenatal stress has a high impact on autonomic dysfunction. Further, sex plays another role—when the maternal cytokine profile was altered, it let do a higher likelihood of depressed daughters but not depressed sons, indicating a sex linkage.

Ultimately, Dr. Goldstein concluded that we do not know enough about sex differences in the brain and how to treat them. Medicine still treats men and women under a singular paradigm, which uniquely harms women—80% of adverse drug reactions are in women. Hopefully, more research into the sex differences will continue to occur, in order to optimize medical treatments.