Body and Brain

Sex and gender are not the same thing. Sex is biological: chromosomes, hormones, anatomy and physiology. Gender covers identity, expression and the social expectations placed on people. Both can shape who develops a disorder, how it shows up and how it is treated.

Sex hormones change across the lifespan. Estrogen and progesterone rise at puberty, cycle each month, surge in pregnancy, drop sharply after birth and fall again in perimenopause. These are the same windows when some women first develop, or see a worsening of, depression, anxiety and other conditions. In some people the brain seems unusually sensitive to these normal shifts.

The stress system (the HPA axis: hypothalamus, pituitary, adrenal glands) talks to the sex-hormone system. In animal studies, estradiol tends to boost the stress-hormone response, while testosterone tends to damp it down. This may help explain why depression and anxiety are more common in women.

For decades, research leaned on male animals, male cells and, before the 1990s, often left women out of clinical trials. A 1977 FDA guideline kept women of childbearing potential out of early drug trials. The NIH Revitalization Act of 1993 made including women in NIH clinical research a legal requirement, and since January 2016 the NIH Sex as a Biological Variable policy expects researchers to factor sex into the design, analysis and reporting of animal and human studies.

This page uses a simplified two-body teaching model. Real people are more varied. Some people are intersex, with sex traits that do not fit typical male or female patterns (about 1.7% by one estimate, though estimates vary), and transgender people may have hormone levels or anatomy that differ from what either model shows. NIH notes that intersex and transgender people have often been left out of research, so much less is known about them.