Estrogen and Testosterone
You love them, you hate them. (cw: mentions of Nazism)
Male and female. Masculine and feminine. Testosterone and estrogen.
The gender binary is not only central to most (fellow enbies I see you) people’s understanding of themselves but also literally being enacted into law. Binaries around gender are built upon patterns of individual traits that reduce the population to two distinct and non-overlapping types of people. The linguistic history of the word gender supports this. If I had a time machine and interviewed a natural scientist that lived between the 15th to 19th centuries, he (almost exclusively a he) would understand the word “gender” to be synonymous to the concept of genus in the classification of living organisms. In this obsolete definition, every human being would have the genus of Homo. {insert joke about gay}
I want to be clear: asserting gender as a binary is reductive and leaves out the lived experiences of a lot of people. And an individual’s sense of their own gender is not merely dependent on their biology. Yet, biology is a central argument cited by those promoting the hegemonic gender binary. But this argument is flawed if you consider the biology at a deeper level than a middle school science textbook. So, let’s start that journey today by going over two of the highlighted vocab words in that middle school science textbook: estrogen and testosterone. These are small molecules that travel through your bloodstream to every organ in your body and change the way your cells are functioning. We have all heard of them, and we all have both floating around in our bloodstream right now (regardless of your sex assigned at birth, gender identity, or anatomical repertoire). But what even are these molecules? Where do they come from?
Fun! with biochemistry
It is actually misleading to refer estrogen in the singular form because the word refers to collection of small molecules. Humans naturally produce four of them: estrone (also called E1), estradiol (E2), estriol (E3), and esterol (E4). These estrogens are distinguished from each other by the composition of atoms and their association with body states. Estradiol is the most common in non-pregnant folks, particularly from puberty to menopause. When a person is pregnant, estriol and esterol predominate, while estrone levels rise during menopause. Estradiol is also commonly prescribed to both cis and trans folks as hormonal birth control, postmenopausal therapy, or hormone replacement therapy.
These molecules also differ in their atomic composition. Estrone, estradiol, estriol, and esterol all have 17 carbon atoms arranged in four conjoined rings. The structural differences are in the number of side chains on the carbon rings. Essentially, side chains refer to common groups of atoms that get stuck on a larger molecular structure. In the case of estrogens, the larger molecular structure is the carbon rings and the side chains refer to collections of oxygen and hydrogen atoms. Due to these differences in structure, each form of estrogen has a different level of potency. Estradiol elicits the strongest effects on the body which is why it is the most prescribed form.
In contrast, testosterone refers to a single hormone that belongs to a class of hormones called androgens. Testosterone is the most highly concentrated sex hormone in the blood regardless of gender or sex assigned at birth.1 However, there are other androgens that are important to note: dehydroepiandrosterone (DHEA), androstenedione (A4), androstenediol (A5), and dihydrotestosterone (DHT). Unlike the estrogens, these different structures are not believed to be associated with different body states or life histories. However, total androgen levels tend to be highest around puberty and decrease with age. The chemical structure of androgens are centered around a similar four-ring structure as the estrogens, but now with 19 carbon atoms. Different androgens also have different side chains, the resulting variations in chemical structure translate to varying potency. For example, DHT is more potent than testosterone.
Additionally, testosterone is prescribed to people of all genders for a variety of reasons including but not limited to: growth stimulation, osteoporosis treatment (particularly in postmenopausal cis women), androgen replacement therapy (typically in cis men and women), and hormone replacement therapy (for transmasculine folks). The vast majority of people who supplement androgens do so via a medical prescription. Yet, some athletes use androgens as anabolic steroids to promote strength though muscle growth. Anabolic steroids use are banned by all major organized sports leagues including the International Olympic Committee and the NCAA.
Hormonal fluidity
Estrogens and androgens as classes of sex hormones is much more complicated that the estrogen and testosterone as a hormonal basis for binary, immutable sexes. In fact, from this understanding we can think of each person as having distinct concentrations of the 9 major sex hormones that is dependent on time, genetics, life stage, and prescription medication. The specific constellation of hormone levels is unique for each person. Since each hormone has a unique potency, total androgen and estrogen calculations can mask important differences. Let’s take a look at the following example:
These two gingerbread cutouts have different hormonal compositions despite having the same total androgen and estrogen concentrations! In particular, the cutout on the right has higher concentrations of the most potent androgen (DHT) and the most potent estrogen (E2). This means that cookie is going to be very sensitive to the bodily effects of the sex hormones.
There is another important twist in the biology that completely upends any notion of a “hormonal binary.” This wrinkle lies in how androgens and estrogens are naturally synthesized.
In the body, androgens and estrogens are generated from cholesterol (yes, that cholesterol) through a series of chemical reactions mediated by various of enzymes. One important enzyme in this process is called aromatase. Aromatase is encoded as a gene cyp19a1 located on Chromosome 15, and its protein form can turn testosterone into estradiol and androstenedione into estrone. Aromatase can also catalyze the reverse reactions (estradiol into testosterone and estrone into androstenedione). Therefore, any cell that contains the Aromatase protein can directly turn an androgen in to an estrogen or vice versa. In fact, the synthesis of estrogens requires the body to first make an androgen precursor. The existence of aromatase is a reminder that androgen/estrogen balance is not static, and a single molecule can be readily switch from one class to another under the right conditions. In fact, its fair to think about sex hormones as being in a constant state of fluidity, with individual atoms moving between androgen and estrogen subtypes depending on their interactions with various enzymes that are encoded in the genome.
Finch me! I must be dreaming.
Genetics, biochemistry, and pharmacology all play important roles in regulating the levels of estrogens and androgens in the body. However, social interactions have also been shown to change the relative concentrations of estrogens and androgens in hyperlocal regions of the body.
One of the best examples of this is in male zebra finches. Researchers inserted tiny probes into the brains of the finches, allowing the researchers to measure the amount of estradiol in small brain regions. The finches were then allowed to hang out with some female finches. This interaction quickly increased estradiol levels in the part of their brain that processes auditory information. Interestingly, the same effect was seen when the male finches listened to another male’s song. This protocol also allowed these researchers to measure testosterone under the same experimental conditions. In fact, as the male finches were listening to the song of another male, testosterone levels decreased in the same auditory brain region. The researchers believe this rapid and opposite change in estradiol and testosterone levels is due to the function of Aromatase which is present in the cells of this brain region.
This study is not evidence that the same change happens when humans are in an analogous situation. But, it does suggest that estradiol levels are responsive to specific life experiences. So, we can add social experiences as another factor in determine someone’s hormonal fluidity.
A brief history lesson
The history of the chemical isolation of estrogens and androgens is worth noting here. Adolf Butenandt is credited as the person who “discovered”2 the structures of the first androgens and estrogens, and Leopold Ružička identified the biosynthesis pathway of androgens from cholesterol. For this work, they were jointly awarded the 1939 Nobel Prize in Chemistry. In particular, Butenandt’s legacy is notably dark due to his ties to the Nazi Party.
In 1933 (two years before he published his testosterone structure), the Nazis burned the library of the Institut für Sexualwissenschaft in a raid that was captured in the now famous photograph of Nazi book burning. The institute, under the direction of Magnus Hirschfeld, performed affirming surgeries on gender non-conforming patients. The attack on the institute began a crackdown by the Nazi regime on German academics. So, six months later (and eighteen months before publishing the work that would win him a Nobel Prize), Butenandt signed a vow of allegiance to Adolf Hitler and the Nazi state. He was rewarded for that pledge.
In 1936, Butenandt became the director of the Kaiser Wilhelm Institute (now the Max Planck Institute for Biochemistry). Under his leadership the institute aligned its research with Nazi pursuits of war and genocide. He funded these pursuits through licensing his strategies for sex hormone purification to the German pharmaceutical company Schering (which merged with Bayer in 2011). By 1939, over 10% of the Kaiser Wilhelm Institute’s budget came from Butenandt’s contracts with Schering.
This history is a reminder of the role of the state in deciding which scientific knowledge is worth investigating. Whereas Hirschfeld’s science ran counter to the gender politics of fascism, Butenandt’s work allowed the German pharmaceutical sector to expand into the manufacturing and sale of sex hormones. This expansion directly benefited the Nazi regime through increased economic power and enhanced investment into warfare at the Kaiser Wilhelm Institute. Butenandt exchanged his scientific knowledge for proximity to power, money, and elite political status.
What did we learn today?
Ok back to the queer science. What does the biology of estrogens and androgens teach us about how our bodies function? I think there are a few interesting takeaways:
The collective action of sex hormones in the body is not a pure dichotomy. Yes, there are two poles, but both androgens and estrogens have multiple members with unique potencies and associations with body states.
These hormonal compositions exist in a state of fluidity as the body has enzymes that modify hormones to give them a new identity. The most striking example is the enzyme Aromatase which directly changes androgens into estrogens, vice versa.
Social experiences also influence the levels of sex hormones! The zebra finches taught us that genetics and biochemistry are just part of sex hormone regulation.
Science is often closely intertwined with politics and state building. Governments determine which research is worth pursuing, individual scientists can use their expertise to bolster their own social or political status.
“Estrogen and testosterone” sounds nice and fits into cisnormative explanations of human difference, but ultimately this is an oversimplification. On this, the lived experiences of queer folks and the underlying biology agree.
This is what stuck out to me. What were your takeaways?!
Yes, even folks who have a hormonal composition medically considered “feminine.”
Science tends use the word “discover” to describe intellectual contributions of scientists. That word is fraught with a history of attribution to only White Europeans explaining their work to an audience of White Europeans.
The first link (or the text on it) seems to be incorrect? As I understand there already is a gender binary enforced in Florida licenses (and all other states), the linked page is about not being able to change between the binary options at whim. But the reality is the options are binary so the linked article is not quite related to the text around it.