June 04

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Hormones: What Boys and Girls are Made of?

Once upon a time, a little boy named Bruce was born. The boy had the promise of a happy, normal life, until one day during a botched medical procedure his penis was destroyed beyond repair. His parents searched desperately for help, worried about little Bruce’s future. Their search led them to a psychologist who assured them that Bruce’s life could still be normal… as long as it was the life of a girl.

And so, Bruce became Brenda. His testes were removed, a vaginal reconstruction surgery was planned, and he was raised as a girl. And yet, despite everything in his environment assuring him that he was female, Bruce never felt like a Brenda. He felt out of place in dresses, with dolls, acting in traditional “feminine” ways. When his parents finally told him about his birth as Bruce, 14-year-old Brenda decided to live out the rest of his life as a man. He got sex reassignment surgery several years later and married a young woman named Jane.

Bruce’s story is more than an anecdote about gender mismatch; it is a well-known case study that changed the way scientists think of gender[1]. Back when Bruce was born (1965), gender was often considered a purely social construct, particularly by the psychologist who suggested his reassignment. Bruce’s transition into Brenda was reported as proof of this hypothesis; gender was learned, something malleable and controlled entirely by environment. When Bruce transitioned to a male identity, however, the exact opposite was evidenced: something other than nurture was contributing to Bruce’s gender. But what were scientists missing? What makes a person feel a certain gender?

One possible contributor is nurture’s old friend nature. In addition to the fact that Bruce’s story was unique –he was forced into a female identity– Bruce differed biologically from the girl his parents raised him to be. One key difference was his hormone levels, which begs the question: to what extent are gendered behaviors controlled by those tiny molecules called hormones?  

Before we forge ahead, it is important to define sex versus gender differences as they are distinct, and yet hormones influence both. Sex differences are physical (e.g. genitalia, differences in hair growth) or related to sex itself (e.g. sexual behaviors). Gender differences are cultural, social, and related to nonsexual behavior (e.g. temperament, what activities you prefer), and can be thought of as what –traditionally speaking– defines masculinity versus femininity[2].

Of course, this “traditional” view of gender is just that: traditional. Outdated. Overly simplistic. Femininity and masculinity form a continuum that are marked by these terms’ “traditional” definitions. Yet, hormonal studies regarding gender typically mark behavior as either “female” or “male”, as studying what falls in between (though important) is a great deal more complicated; I will thus refer to gender in a binary fashion for the rest of this article. (For a look at nonbinary gender research, click here.) Fear not! There is still much to learn from these simplified studies about how hormones affect women and men.

Gender: What do hormones have to do with it?

Children are heavily influenced by gender stereotypes at an early age. They learn to dress in pink or blue, to pick up the truck or the doll. With so much social influence bombarding kid’s behaviors, how much does biology actually contribute?

Sexual dimorphisms, observable differences between males and females of a single species, have long been investigated and are known to exist by the hundreds. Some of these dimorphisms reside in the brain itself, ranging from certain area’s sizes (e.g. men have larger amygdala, the region associated with emotion), to cell density (e.g. women have more neurons in language areas)[3]. Given the differences in our brains, biology’s influence over “dimorphic” behaviors may be larger than once thought.

Many studies attempt to parse apart environmental and biological influences on gender by investigating children at an early age, before society can interfere. Such studies have found numerous differences between boys and girls, ranging from activity level to ability to inhibit responses[4]. In one particularly interesting study, scientists measured how long baby boys and girls stared at “gender-specific” toys (e.g. dolls versus trucks). Babies typically stare longer at objects they prefer, and surprisingly, little girls stared longer at dolls than trucks[5]. Though not completely definitive (baby boys didn’t show a strong preference for either toy, though they preferred trucks more and dolls less than baby girls), these results may indicate that this persistent stereotype originates from more than societal pressure. Even more shockingly, “gender-specific” toy preference has been shown in monkeys as well. When baby monkeys were exposed to either dolls or trucks, the males played more with trucks and the females more often reached for the dolls[6].

By what mechanism could biology be influencing these gender-specific preferences? This is where hormones enter the picture. In a follow-up study, children who played with their favorite toys (similar to the baby monkeys) were tested for testosterone levels using comparisons of 2nd-to-4th finger length ratios as a proxy (a useful, if mysterious, effect of testosterone)[7]. Boys and girls with a smaller ratio –indicating more testosterone– were more likely to play with “male-specific” toys, indicating an interaction between “gendered” behavior and hormone levels[8].

I know that this is hard to swallow. I mean, female monkeys preferring Barbies? I, who have never liked dolls, initially felt rather offended by the whole idea.  According to these studies, was I full of testosterone or just an outlier? Surely, I thought, it was all hogwash. But then, I suspended disbelief and read a bit more. It turns out that the effect of gendered preferences in young monkeys and children has been replicated multiple times [6,9,10], and one lab even found that girls with abnormally high levels of testosterone prefer stereotypically male toys [11]. Though this research is not without its flaws (the effect sizes are not exactly overwhelming), its findings suggest that hormones might influence not only sex differences but gender differences as well. Something significant may be happening between hormones and gender, and it is important to put on our science caps and (though difficult) try to view gender research objectively.

If we accept that hormones are affecting gender preferences, the question becomes: how? A clue may reside in the brain’s sexual dimorphisms. Sex hormones are molecules that influence reproductive organ growth and secondary sex characteristics (e.g. hair growth, anything that would be a “sex difference”). It turns out that brain areas that show sexual dimorphisms also have high levels of sex hormone receptors (proteins that bind to sex hormones and cause changes in a cell’s genetic expression)[3]. In addition, a group from University of California, San Francisco has shown that turning off genes that are specifically upregulated by these sex hormones can curtail gender-specific behaviors such as male aggression or female maternal care. (See a video explanation here.)[12]. And, of course, hormone levels themselves differ drastically between men and women[13]. So, on multiple levels, evidence suggests that hormones guide us towards “masculine” and “feminine” mannerisms. Which hormones are the main contenders?

Boys will be boys?

        Boys will be boys?

Testosterone

            Did you know that when a fetus is in the womb, it will naturally develop female sex organs? At first, the fetus will have no sex differences other than XX versus XY, having only a “gender-neutral” genitalia precursor. Without a hormone spike, the fetus will automatically develop female sex organs and characteristics. If the fetus has a Y chromosome, however, developmental events will lead to a large increase in androgens (male sex hormones) compared to female fetuses, triggering development of male sex organs and characteristics. Among these gender-defining androgens is testosterone, the hormone best known for its illegal use in sports. Testosterone (and other androgens) will “bathe” the XY fetus during development, masculinizing the fetus from body to brain[14].

Fetal testosterone levels have been tied to the “manliness” of a number of behaviors. More “masculine” digit ratios (remember, an indirect measure of fetal testosterone) predict higher activity levels and higher levels of aggression[15]. Sometimes, female fetuses are accidentally exposed to too much testosterone in the womb. Girls with this condition, congenital adrenal hyperplasia (CAH), are more aggressive, more likely to prefer boy’s toys, and (predictably) have more masculine digit ratios than girls without CAH[11, 16]. Testosterone may be a key player in determining “manly” attributes.

Comparison of typical 2D (2nd finger) to 4D (4th finger) ratios in a male and female. Women with CAH will have 2D:4D ratios, as well as behavioral attributes, that are more stereotypically masculine than women without CAH.

Comparison of typical 2D (2nd finger) to 4D (4th finger) ratios in a male and female. Women with CAH will have 2D:4D ratios, as well as behavioral attributes, that are more stereotypically masculine than women without CAH.

Estrogen

Estrogen, the best known “female hormone”, also has a strong influence on behavior. Unlike testosterone, the level of estrogen fluctuates rapidly in women, bouncing up to ten times its “resting” level in the middle of the menstruation cycle and subsequently plummeting[17]. This rapid and drastic drop-off in estrogen levels has been tied to many cognitive changes, including increased anxiety, memory changes, and different sleep patterns[18]. These are similar symptoms to those of menopause, during which estrogen levels fall substantially[19].

How can we further study estrogen’s influence? This is where our handy friend the lab rat comes in. Female rats have a menstrual cycle like humans do, but with an extremely sped up process called “estrus” that lasts only 4-5 days per cycle[20]. Female rats can be measured for behavioral and biological changes at various stages in the cycle, helping uncover what it is that estrogen is really doing to female behavior. In one study, female rats were exposed to TMT (a smelly molecule in coyote pee, terrifying to any rat) at various stages of their “estrus cycle” and assessed for behavior and brain activity[21]. During estrus (when estrogen nosedives) the rats were found to freeze more, implying that they were more frightened by the TMT. Brain areas related to fear showed more activity during estrus, indicating that rats may be experiencing more fear during this estrogen dip. Estrogen could have a quick and powerful effect on mood and behavior.

Both rats and humans feel more anxiety when estrogen levels fall.

Both rats and humans feel more anxiety when estrogen levels fall.

Researching the Effects of Hormones on Gender: What is it Good for?

This article only scrapes the surface of the “gendered hormone” literature. Hormone systems (like brain systems) are extremely complex, changing throughout time of day, day of life, state of mind, and more; studying the interplay between the brain and hormones (called “neuroendocrinology”) is an often correspondingly difficult field of study. Despite the challenges, scientists still have found many, many reasons to believe that hormones can influence our gender-specific behaviors and so define us as “masculine” and “feminine”. Gender may not just be a societal construct, but something that is defined by biology, something that is in our DNA, our blood, our brains.

But we need to be careful. As with all cool science findings, it is very easy to get carried away with our interpretations, and with gender research inflated findings can be particularly problematic. Too easily can “Estrogen Level Fluctuations during Estrus Influence Female Rats’ Fear” become “Women have Volatile Mood Swings due to their Changing Estrogen Levels”. See how dangerous that jump in logic was? Now not only are women emotionally turbulent, it has been evidenced by science. We don’t want to be careless and enforce sexist (and flat-out false) stereotypes by skewing gender studies. What you should take away from this article is that men and women are different in more ways than just their genitalia. Hormones help make our minds different, which means our actions, feelings, and thoughts are different too.

Screen Shot 2015-05-27 at 3.46.14 PM

                Science: you’re doing it wrong.

References

Title Image: http://dr-lobisco.com/?s=breast+cancer

Monkey with Truck:

http://www.livescience.com/22677-girls-dolls-boys-toy-trucks.html

Finger Ratios: https://www.msu.edu/~bjlab/androgens.html

Estrus/Menstrual Cycle: http://www.nature.com/neuro/journal/v8/n6/images/nn0605-697-F1.gif

Rat Mothers: https://adonis49.wordpress.com/2013/06/11/take-seriously-grandmas-experiences-they-significantly-affected-your-behaviors/

Female/Male Brains: http://genderspectrum.weebly.com/media-portrayal-of-gender-stereotypes.html

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