Summary: Male individuals with isolated GnRH deficiency (IGD), a rare hormonal disorder that causes diminished sex-hormone exposure beginning in the second trimester, report higher levels of childhood gender non-conformity than males without IGD. Females with IGD did not show this difference.
Source: Penn State
Researchers investigated whether early prenatal sex-hormone exposure contributes directly to sex-typed childhood behaviors in humans. While laboratory studies in animals show that sex differences in hormone levels shape developing brains and later behavior, studying this process in people is challenging. The team used a natural experiment—isolated GnRH deficiency (IGD)—to study these effects in humans.
Isolated GnRH deficiency (IGD) is a rare endocrine condition in which individuals have markedly reduced production of gonadotropin-releasing hormone beginning in the second trimester and continuing until they receive hormone replacement therapy to induce puberty. Importantly, the external genitalia form earlier in the first trimester, so people with IGD are unambiguously male or female at birth and are typically raised accordingly. Their condition is usually identified later when expected puberty does not occur.
This developmental pattern creates a natural contrast: people who were raised as boys but experienced unusually low testicular hormone exposure during early brain development, and people raised as girls who experienced low ovarian hormone exposure. By comparing these individuals with those who had typical hormonal development, the researchers aimed to separate the direct biological effects of prenatal hormones on the brain from social influences tied to being raised as a particular sex.
The study included 97 people diagnosed with IGD and 1,665 participants with typical hormonal development. Because IGD affects about one in 130,000 people, recruiting a large clinical sample was difficult; participants with IGD were identified through collaborations with clinical centers, research hospitals, and IGD support communities.
To assess sex-typed childhood behavior, participants completed retrospective measures asking about their childhood play preferences and social choices. Questions asked whether, as children, they tended to identify with male or female characters in stories, whether their friends were mostly boys or girls, and whether they preferred toys typically associated with boys (for example, trucks) or girls (for example, dolls). These childhood gender role behaviors represent some of the largest and most reliable sex differences in behavior.
The main finding was sex-specific. Men with IGD reported more childhood gender non-conformity than men without IGD, indicating a higher degree of divergence from typical male-typed play and social patterns. In contrast, women with IGD did not differ from typical women in their reported childhood gender role behaviors. This asymmetry suggests that early exposure to androgens—male sex hormones such as testosterone produced by the testes—has a direct influence on brain development linked to male-typical childhood behaviors, whereas reduced ovarian hormones in early development did not show a comparable effect on female-typical behaviors in this sample.
“In the lab, you can manipulate hormones and observe direct effects on developing animal brains,” said David Puts, associate professor of anthropology. “Because we cannot perform those manipulations in humans, IGD offers a rare natural experiment to probe whether prenatal sex hormones shape later gendered behavior.”
Talia N. Shirazi, a doctoral recipient in anthropology who contributed to the work, added, “We asked people to recall simple childhood preferences—who they played with, which characters they identified with, and the types of toys they chose. These measures are robust indicators of childhood gender role behavior. The pattern we observed in males with IGD supports the role of prenatal androgens in organizing male-typical behavior.”
The authors caution that the sample of people with IGD is modest because of the disorder’s rarity, but they note the consistency of results across participants recruited from clinical settings and community support groups. Both direct hormonal effects on the developing brain and gender socialization—how children are encouraged to play and behave according to their assigned sex—likely contribute to sex differences in childhood behavior, the researchers write.
The study’s findings reinforce the idea that androgens can exert a direct organizational influence on neural development in humans similar to what has been shown in other mammals. At the same time, the absence of a clear effect among females with IGD highlights the complexity of hormonal and social contributions to gendered behavior and suggests that reduced prenatal ovarian hormones do not produce the same pattern of change in childhood gender roles as reduced androgens in males.
The research team emphasizes the need for additional studies and earlier identification of IGD cases to expand understanding of how prenatal hormones contribute to gender-related development. Improved recruitment strategies and longitudinal designs could clarify the timing and mechanisms through which hormones and socialization interact to shape childhood behavior.
Other contributors from Penn State included Heather Self, Kevin A. Rosenfeld, Khytam Dawood, and Rodrigo Cárdenas. Additional collaborators were Lisa L. M. Welling, J. Michael Bailey, Ravikumar Balasubramanian, Angela Delaney, and Marc Breedlove.
Funding: This research was supported by the National Science Foundation, the National Institutes of Health, the Penn State Social Science Research Institute, and the American Institute of Bisexuality.
About this neurodevelopment research news
Author: A’ndrea Messer
Source: Penn State
Contact: A’ndrea Messer – Penn State
Image: The image is credited to Patrick Mansell, Penn State
Original Research: The study will appear in Psychological Science