The brain’s reaction to male odor shifts at puberty in children with gender dysphoria

The brains of children with gender dysphoria react to androstadienone, a musky-smelling steroid produced by men, in a way typical of their biological sex, but after puberty according to their experienced gender, finds a study for the first time in the open-access journal Frontiers in Endocrinology.

Around puberty, the testes of men start to produce androstadienone, a breakdown product of testosterone. Men release it in their sweat, especially from the armpits. Its only known function is to work like a pheromone: when women smell androstadienone, their mood tends to improve, their blood pressure, heart rate, and breathing go up, and they may become aroused.

Previous studies have shown that, in heterosexual women, the brain region that responds most to androstadienone is the hypothalamus, which lies just above the brainstem and links the nervous system to the hormonal system. In men with gender dysphoria (formerly called gender identity disorder) – who are born as males, but behave as and identify with women, and want to change sex – the hypothalamus also reacts strongly to its odor. In contrast, the hypothalamus of heterosexual men hardly responds to it.

Girls without gender dysphoria before puberty already show a stronger reaction in the hypothalamus to androstadienone than boys, finds a new study by Sarah Burke and colleagues from the VU University Medical Center of Amsterdam, the Netherlands, and the University of Liège, Belgium.

The researchers used neuroimaging to also show for the first time that in prepubescent children with gender dysphoria, the hypothalamus reacts to the smell of androstadienone in a way typical of their biological sex. Around puberty, its response shifts, and becomes typical of their experienced gender.

The reaction to the smell of androstadienone in the hypothalamus of 154 children and adolescents, including girls and boys, both before (7 to 11-year-old) and after puberty (15 to 16-year-old), of whom 74 had been diagnosed with gender dysphoria.

Results showed that the hypothalamus was more responsive to androstadienone in 7 to 11-year-old girls than in boys, both without gender dysphoria, although not yet as much as in adolescent girls. This means that the greater receptiveness of women to its odor already exists before puberty, either as an inborn difference or one that arises during early childhood.

Before puberty, the hypothalamus of boys with gender dysphoria hardly reacted to the odor, just as in other boys. But this changed in the 15 to 16-year-olds: the hypothalamus of adolescent boys with gender dysphoria now lit up as much as in heterosexual women, while the other adolescent boys still did not show any reaction. Adolescent girls with gender dysphoria showed the same reaction to androstadienone in their hypothalamus as is typical for heterosexual men.

These results suggest that as children with gender dysphoria grow up, their brain naturally undergoes a partial rewiring, to become more similar to the brain of the opposite sex – so corresponding to their experienced gender.

Humans have a nose for gender

The human body produces chemical cues that communicate gender to members of the opposite sex, according to researchers who report their findings in the Cell Press journal Current Biology on May 1. Whiffs of the active steroid ingredients (androstadienone in males and estratetraenol in females) influence our perceptions of movement as being either more masculine or more feminine. The effect, which occurs completely without awareness, depends on both our biological sex and our sexual orientations.

"Our findings argue for the existence of human sex pheromones," says Wen Zhou of the Chinese Academy of Sciences. "They show that the nose can sniff out gender from body secretions even when we don’t think we smell anything on the conscious level."

Earlier studies showed that androstadienone, found in male semen and armpits, can promote positive mood in females as opposed to males. Estratetraenol, first identified in female urine, has similar effects on males. But it wasn’t clear whether those chemicals were truly acting as sexual cues.

In the new study, Zhou and her colleagues asked males and females, both heterosexual and homosexual, to watch what are known as point-light walkers (PLWs) move in place on a screen. PLWs consist of 15 dots representing the 12 major joints in the human body, plus the pelvis, thorax, and head. The task was to decide whether those digitally morphed gaits were more masculine or feminine.

Individuals completed that task over a series of days while being exposed to androstadienone, estratetraenol, or a control solution, all of which smelled like cloves. The results revealed that smelling androstadienone systematically biased heterosexual females, but not males, toward perceiving walkers as more masculine. By contrast, the researchers report, smelling estratetraenol systematically biased heterosexual males, but not females, toward perceiving walkers as more feminine.

Interestingly, the researchers found that homosexual males responded to gender pheromones more like heterosexual females did. Bisexual or homosexual female responses to the same scents fell somewhere in between those of heterosexual males and females.

"When the visual gender cues were extremely ambiguous, smelling androstadienone versus estratetraenol produced about an eight percent change in gender perception," Zhou says, a statistically very significant effect.

"The results provide the first direct evidence that the two human steroids communicate opposite gender information that is differentially effective to the two sex groups based on their sexual orientation," the researchers write. "Moreover, they demonstrate that human visual gender perception draws on subconscious chemosensory biological cues, an effect that has been hitherto unsuspected."