The History of Hormones

From metabolism to sex drive, hormones come in tiny packets that pack a powerful punch, and yet there is a lot of misinformation about these chemicals. So Randi Hutter Epstein, a doctor and medical writer, decided to set the record straight. The result is her book Aroused: The History of Hormones and How They Control Just About Everything.

Though we throw around the world “hormonal” today, the concept didn’t exist before the 1900s. In the past century, we’ve gone from not knowing what these glands secreted to selling hormonal sprays that promise to make it easier to seduce. How did we get here?

The Verge spoke to Epstein about the short history of hormones, how they were involved in the “crime of the century,” and how we sometimes give them far too much credit today.

AC : The word and concept of “hormone” only date back to 1905. Before that, what did we believe was regulating our bodies?

RHE : We’ve always wondered what makes our bodies function correctly. There was this horrible, weird time of history in America in the late 1800s when doctors started looking at these so-called “circus freaks.” These were people with disabilities or something wrong with them, like the bearded lady or fat lady. They were being put in the circus, and at the same time, doctors were saying maybe they have some sort of glandular disorder.

It’s not like the “nice doctors” versus “mean circus people.” The circus was paying and doctors were researching them and not really helping them. So these doctors who studied anatomy for years saw glands in the body — like the thyroid and adrenal gland — but we didn’t understand what we did. Until the early 1900s, we thought that everything marched along nerves like marching along train tracks, or went through the blood like a raft going down a river, and then it’d just bang into wherever it’s needed.

Hormones are these internal secretions that come out of a gland, and they go through the blood, but they go to a specific target. This was controversial, and there were people saying it can’t be because how do they know where they’re going? I like to talk about hormones like your internal Wi-Fi because they have these signals that allow them to go to places.

AC : Why didn’t we know about them before? What technology really changed the study of hormones?

RHE : The huge technological advance happened in the late 1950s and really took hold in the mid-‘60s and early ‘70s. It was the ability to, for the very first time, measure hormones down to the billionth of a gram. That’s like if you took a gram of salt and threw it into the ocean, and it had a powerful impact.

It wasn’t that we could sort of measure hormones before this, and then we precisely measured them. Before this, we couldn’t measure hormones at all, and it was all guesswork. This technology, which is called RIA (radioimmunoassay) has made it possible to measure things we thought too scarce to measure. We wouldn’t have been able to find HIV in blood if not for RIA. We wouldn’t be able to track cancer markers.

The other part of the story that I love about this technology is that the co-creator, Rosalyn Yalow, graduated top in her class in physics but was told to be a secretary. So she became a secretary for a scientist at Columbia, and only eventually got into the PhD program at the University of Illinois because there were some open spots because the men were gone for World War II. As she told a biographer, “They had to have a world war for me to have a graduate degree.” The rest is history. She revolutionized modern medicine, won a Nobel, and was very supportive of other women becoming scientists.

AC : So RIA lets us measure a billionth of a gram of hormone. Do we need that level of precision? Can that really make the difference?

RHE : Yes, hormones come in tiny packets. When we say you have too much of this hormone or a lack of another hormone, we are talking in terms of nanograms. They’re potent. We’re not talking about extra pounds of hormones.

AC : Are some more powerful than others, if that question makes sense?

RHE : The way to think about it is that most hormones don’t work on their own. There’s a chain of hormones, helper hormones, “factors.” There are different types that are super powerful and interact with each other, which is how things get super complicated, and you can have a glandular issue that has nothing to do with estrogen, but it’ll screw up your fertility because it’s all connected.

AC: Are we still discovering new hormones?

RHE : Absolutely. In the 1990s we discovered leptin, which is the appetite hormone. We discovered it comes from fat cells, which was shocking because most people think fat cells are just blobs of butter you can remove. We’re still learning about hunger and appetite hormones, and there’s a new insulin growth factor, too. I think, in the future, we’re going to be learning more about hormones and behavior, like hormones that impact basic drives to eat, to lust, and so on.

AC : Speaking of behavior, one fascinating part of the book was about the trial of Leopold and Loeb, and how people tried to defend them saying, “The hormones made them do it.” What precedent does this kind of approach mean for hormones and crime and law?

RHE : The trial was in the 1920s and called the “crime of the century” because it was two rich kids who murdered another rich kid. You couldn’t measure hormones then. It was speculative, and it didn’t work as far as the judge was concerned.

From a scientific perspective, we’re still looking into this. Do I think this will get people off murder? Probably not. I don’t think we’ll ever be able to say, “His hormones made him do it.” But from a scientific perspective, it’s fascinating to look at how hormones shape our behavior. And, of course, what they were doing in the 1920s, unsuccessfully, and what we’re still trying to do now, is look at what hormonal imbalances we can detect early on. And perhaps then we can treat it and make sure that we, for instance, prevent killers.

But as I’m saying these words, you can see right away this is a slippery slope. It’s like the designer baby thing. We know hormones control us, and we’d like to control them to the extent they give us quality, healthy lives, like the way we use insulin to help diabetes. But then again, how much control do we need? We don’t want to go the route of eugenics.

AC : What do you think about the way we talk about hormones today? Like all the hype surrounding the “love hormone” oxytocin, for instance.

RHE : We simplify things too much. Too often there’s a seed of fascinating scientific discovery. And before that seed has time to blossom, there are people who glom on and extrapolate way too far. With oxytocin, yeah, it probably does have to do with human mother-baby bonding, but we’re taking a major leap to say, “You can buy an oxytocin love spray.”

There are some clues that oxytocin impacts behavior. It might augment that feeling that you have, but it could turn hate into more hate instead of necessarily hate into love. People are hoping that giving oxytocin to children on the autistic spectrum would help them, but so far, it hasn’t been very successful. So I’m not saying we shouldn’t do this research, but it’s very different from purchasing something over the counter that might not even have oxytocin in it. It could just be water.

How hormones went from theoretical to overhyped in one century. By Angela Chen. The Verge , August 7,  2019. 

Lulu Garcia-Navarro  (NPR) talks with Dr. Randi Hutter Epstein about her new book Aroused, which tells the story of the scientific quest to understand human hormones.

The Scientists Who Explore Human Hormones In 'Aroused'.  NPR,  July 1 , 2018. 

Website Randi Hutter Epstein

This is a well-written and informative book about the history of hormone research. The interested reader will learn how scientists have come to understand what hormones are and how they function. But it is also deeply disturbing: for what this history entails, for how the author tells it and for what she leaves out.

“Aroused” is organized around scientific and medical episodes from the 19th century to the present, many of which involved dubious and unethical practices. Among the central characters are doctors who promoted vasectomy to enhance male youthfulness, who operated on patients without their knowledge and who experimented on their own children. Randi Hutter Epstein, the author of “Get Me Out: A History of Childbirth From the Garden of Eden to the Sperm Bank,” tells us of a journalist paid by a doctor to ghostwrite glowing articles about testosterone therapy and of a physician who kept a 17-month-old baby boy in the hospital for a month while he performed experimental genital surgery without parental support; the doctor then sent the child home instructing the parents to expunge all evidence that “she” was ever a “he.”

Even more disturbing than reading about these practices is that for the most part Epstein shrugs them off, saying that the physicians involved were well intentioned, that what they did was appropriate for their day or that they did what they could with the information they had. These were the “best practices of the time.” It was “just the way things were.” But that’s not quite true: Some of these practices were questioned even at the time. And it doesn’t take hindsight to recognize hubris.

In a chapter titled “Pickled Brains,” Epstein seems to delight in the macabre spectacle of abandoned organs in a university basement. The brains were collected for research in the early 20th century; she notes that to handle them now requires compliance with biohazard regulations yet she fails to explain why. Neither does she tarry much over the ethical medical treatment of human remains. Consider Charles Byrne, the so-called Irish giant who in the late 19th century became the object of public attention. Byrne anticipated that after his death, physicians would want to study and perhaps display his body, so he instructed friends to seal his coffin and dispose of it in the ocean. They agreed, but Byrne’s directive was circumvented when the prominent physician John Hunter arranged for the cadaver to be stolen and the skeleton displayed in the Hunterian Museum, London, where it remains today. Numerous historians, ethicists and laypeople have objected to the continued thwarting of Byrne’s wishes; Epstein reduces this complex and important matter to a footnote.

Epstein contrasts “quackery” with “legitimate research,” and “craziness” with “serious science,” but the crucial question of how to distinguish between them is unaddressed. Many of the dodgy practices she describes were undertaken by credentialed medical doctors and scientists. Today, testosterone therapy for virility is endorsed by people with medical degrees, but there is little evidence of its efficacy. Epstein offers no guidance on how we might evaluate the untested or otherwise problematic therapies on offer today. If we were to adopt her stance that this is “just the way things are,” we would have no way to judge, and therefore no basis on which to object to current dubious practices.

Epstein also elides the problem of hormone-disrupting chemicals. Among the reasons hormones long eluded scientific understanding is that they can be effective at minuscule doses, and the body is acutely sensitive to when those doses are released. One of the great advances of late-20th-century science was to understand this; another was to recognize that some synthetic chemicals — most notoriously the pesticide DDT but also many others — can mimic hormones with great adverse effect. (DDT was banned in part because it was killing bald eagles by disrupting their reproduction.)

These chemicals are toxic, but not in the way that lead or mercury or arsenic is. Rather, they alter endocrine function: hence the moniker endocrine-disrupting chemicals or EDCs. The human health effects of EDCs are not entirely understood, but the list of potential problems is long: prostate and breast cancer, infertility, fibroids, endometriosis, male and female reproductive dysfunction, birth defects, disrupted immune function, obesity, diabetes, cardiopulmonary disease, neurobehavioral and learning dysfunctions like autism, hermaphroditism and alternation of sexual identity in animals. One estimate places the cost of the disease burden at $340 billion. Surely a book on the history of hormone research should have something to say about that.

Science or Quackery? The Study of Hormones Has Been Both, a New Book Suggests. By  Naomi Oreskes. The New York Times , August 6, 2018.

“I think I’ll go into wrestling. Blood, sweat, and fighting, that’s me.” I looked at my seven-year-old daughter as we left the playground, that hotbed of jungle activity after school. “Did something prompt this?” I pressed. My child has never expressed an inclination toward blood and sweat, and fighting is something she has historically interpreted as a verbal activity. We entered our destination, the grocery store, and she jumped on the rolling basket so she could ride it from the outside. Then: “It’s just — why are boys so … boyish? What makes them that way?”

As it happened, I had just finished Randi Hutter Epstein’s chatty and absorbing book, Aroused: A History of Hormones and How They Control Just About Everything, out in paperback from Norton. And that was how the old ladies examining the plums at Zabar’s ended up hearing a mother say, “Well, it starts with androgens. When an embryo is XY, it usually responds to hormones in the mother’s blood supply that tell it to grow testes and a penis. Do you want sweet potatoes for dinner? Later on, other hormones come into play.”

Hormones have been on my mind quite a bit of late. Earlier today I sat before a sea of papers, cross-hatched piles of notes and charts. Laundry remained unfolded on the couch. I wanted to eat a pound of cheese for lunch, and no sooner did something occur to me than I had forgotten it, lost in a fog of distraction. Put simply, I have PMS. I begin counting the days at this time, waiting for the near bacchanalian delight of my monthly blood flow. Oh, the release! Oh, the energy! The depression lifts, and I coast into clear-thinking waters! I will no longer study two pages of a newspaper article only to look up and say, “What the hell have I been reading?” I will follow things again — schedules, TV show story lines, a logical order of operations for housework. All this will be from a change in hormones. Two weeks later, my husband and child will marvel at how I’ve vacuumed the living room rug in a perfect pattern, scrubbed the bathtub to a gleaming shine, alphabetized the books by author and arranged them by subject. That’s ovulation. Then I will begin the downward slide once more to PMS. Hormones. They do seem to control everything.

Aroused begins at the turn of the century, when scientists tinkering in the lab began to discover hormones, and how they differ from neurotransmitters: if our nervous system is a highway of linked connections, our endocrine system is what Epstein calls “your wireless network.” Where the book really takes off is in its pointed examination of how social norms and sexual politics have interacted with new discoveries in science. Dr. Louis Berman declared a new field in the 1920s, which he called “Psycho-Endocrinology.” He went on to write a book called The Glands Regulating Personality, in which he suggested that women with irregular periods “will also be aggressive, dominating, even enterprising and pioneering — in short, [they have] masculinized ovaries.” To think: A woman has no chance of being enterprising if she bleeds like clockwork every month! There are plenty of other historical citations here that may make you laugh or cry. In 1924, two doctors, Harold Hulbert and Karl Bowman, from Boston Psychopathic Hospital — yes, that was a real place — were called in to examine Nathan Leopold and Richard Loeb, two teenagers being tried for what had been dubbed, “The Crime of the Century.” They had kidnapped, tortured, and murdered a 14-year-old boy. Other than depravity, there was no motive, but because the case converged with the burgeoning era of endocrinology, a shocked public and an eager defense attorney named Clarence Darrow sought answers in the new field. During the examination, which took eight days, reporters crouched outside the prison. Then Hulbert took the stand to declare Loeb suffered from “multigland syndrome” and Leopold had, among other pathologies, a calcified pineal gland, which accounted for his excessively high libido. Their chief instruments were a metabolimeter and an X-ray machine (the theory being that bones are pushed aside by oversized glands and would therefore show up on X-ray). The judge ultimately decided that it made no difference whether the endocrine experts were right or not. Murder was murder, and criminals could not seek absolution in their biochemistry.

It’s a problem that continues to fascinate us as a society: Does psychopathy excuse certain behaviors? Does it make a crime more or less understandable? Many experts debated the nature of notorious serial killer Ted Bundy’s character — was he a classic psychopath? — and felt they had zeroed in on a crucial question. But had they? Was it just about semantics, or were there important questions of science, treatment, and punishment on the line? Certainly it is interesting to see how the discovery of hormones kicked off a round of this debate, and it is gratifying to see a judge apply a moral code equally.

                                                                       

The most moving chapter of Epstein’s book follows the story of a baby named Brian Sullivan at birth in 1956. The baby was labeled a “hermaphrodite” in his earliest hospital records: he appeared to have both penile and vaginal tissue. At 18 months, the doctor — rather drastically, by today’s standards — performed an exploratory surgery and discovered the child had a vagina, uterus, and ovaries in his abdominal cavity. Without consulting Brian’s parents, he amputated the clitoris and then instructed them to begin raising the child as a girl. Brian became Bonnie. Wardrobe, activities, even room color were switched to the conventional “pink for girls.” And Bonnie promptly stopped talking. As Epstein reminds us, it was a dark time for people born with atypical genitalia. There was very little understanding of the complex processes underlying the hard-wiring of gender identity. Discovering a uterus inside a child did not, in fact, entail the discovery of the child’s gender identity. Later, after further research, it would become clear that an initial spurting of estrogen or testosterone into the bloodstream during pregnancy likely shaped at least some of this hard-wiring. So whatever disrupted Brian’s genital development may also have shaped whom he or she felt herself to be gender-wise. Bonnie’s life was again disrupted medically at eight when she was operated on to remove genital tissue from her abdomen. She was told that it was for her “stomach pains,” though she reports not having any pain at the time. She was admitted to Columbia Presbyterian Hospital in 1964, where photographers took photos of her naked, and where she endured pre-operative pelvic exams. “The fingers in her vagina and anus were mortifying. She felt like a freak,” reports Epstein, who met Bonnie, now called “Bo,” years later. It was many years before Bo unearthed her medical records, finding the crude designation “hermaphrodite” among the other abuses she endured. Eventually, she founded the “Intersex Society of North America,” in the hope of connecting with other people who had suffered similar sorts of mistreatment and aggressive interventions, and consequentially endured lives of loneliness and confusion. She also wanted to inform doctors on how better to manage intersex children. Soon, letters from lonely and discouraged intersex people flooded her post office box. A support network sprang up.

Aroused shows how hormone and surgical therapies hardened a binary gender system. “The data,” however, “were showing a much more complex picture of humanity,” writes Epstein. Christine Jorgensen, born George Jorgensen in 1926, transitioned at 26 from male to female with the help of surgery and hormones. The Daily News broke the story in 1956 and, before long, the Danish doctor who performed the surgery was inundated with requests for help. Americans turned to Dr. Harry Benjamin, an endocrinologist specializing in gender and sexuality. It was Benjamin who would clarify the notion of hard-wiring of the fetal brain toward gender identity as being dependent on hormonal influences in the womb, and would go on to write The Transsexual Phenomenon. (Transsexual is an outdated word, and has since been replaced with the more accurate “transgender.”) He, in turn, referred patients seeking surgery to the Johns Hopkins Gender Identity Clinic. Epstein navigates this topic well, focusing on the complexity of the issue. “[W]hat causes transgender identity in one person may not be the same as in another,” she writes.

Ultimately, the message of Aroused is that we know a lot about hormones, but definitely not everything, which might well have been its subtitle. Enter the quacks, frauds, careless researchers, and others looking for quick payoffs from new discoveries. In nearly every chapter, Epstein stresses the vulnerability of new scientific information about the maintenance of the human body to industry objectives. Hormones were especially vulnerable since they seem to regulate just about every major process, from growth to metabolism, sleep cycles to sex, parenting to the immune system, stress to lactation. From the “revitalizing vasectomies” and “epinephrine suppositories” of the 1920s, to the oxytocin supplements currently being sold as enhancers of both arousal and intimacy (despite no strong evidence that the hormone can be metabolized with a sublingual dose and despite the precise function of the hormone not being known), companies are eager to make a buck by turning new science into ill-gotten profit. Just as we are vulnerable to well-meaning doctors, we are vulnerable to our desires for treatments and cures.

Hormones are tiny drops in a very big ocean, interacting in complex ways with nerve cells and other chemicals in the human body, Aroused warns. Not only do we need to strive for more knowledge but also for accurate testing of that knowledge. We may have come far from the dark days when Blanche Grey, “The Fat Bride,” was put on display in the New York City Dime Museum — for suffering some type of thyroid or pituitary malfunction — or indeed from the days of nonconsensual clitoral amputation of the sort Bo Laurent endured, yet our society still struggles with accepting just how varied our gender spectrum is. My father, who is 80, says he has no trouble with understanding different sexual orientations, or transgender identity, but “nonbinary” is a bridge too far. Meanwhile, my daughter is growing up in a world where people are claiming the pronouns they feel best suit them, and she may be surprised to learn that there was ever a need for adjustment to the notion of a spectrum. We are currently reading A Wind in the Door, the sequel to A Wrinkle in Time, in which Madeleine L’Engle introduces the concept of more evolved creatures who communicate with one another by “kything,” which allows for a more complete understanding of another’s interior world. This strikes me as an apt metaphor for humanity’s expanding definitions of gender identity as science catches up to human experience. At their best, the biological sciences can bring us closer to understanding and helping one another, introducing our differences not as obstacles but bridges.

And then there’s menopause. “Mid-Life Psychosis,” screamed a New York Magazine cover one week in December last year. “45, female, and hearing voices.” The article examined a link between fluctuating hormones — specifically a drop in estrogen — during menopause, and late-onset schizophrenia. The author admits she was at first reluctant to take the topic on (she did not want to be responsible for furthering the trope of the crazy menopausal lady). But, she continues, it became clear that women were once again an underserved community: how hormones affect women’s minds and bodies is little understood because it is little studied. I am 44 myself and, while not yet in menopause, have begun to notice small changes. I still menstruate every month, but I find my moods a little less like clockwork, a bit more unpredictable. I notice increased restlessness, as well as a driving need for solid exercise every day to calm and center me. I notice a decrease in the symptoms of PMS, but find that those blue moods and sudden cramps might take hold of me at other times in the month. Naturally, I was both horrified and fascinated by the possible link between menopause and schizophrenia. Something is definitely happening, I thought. Please let them figure it out. A recent article linking cognitive decline and menopause made the rounds on Facebook, and I eagerly jotted down what I learned, hoping to glean tips on how to reduce my evidently gender-determined chances of developing dementia. I’ve already added Darcey Steinke’s new book on her own experience with menopause, Flash Count Diary, to my to-read-immediately pile.

Epstein’s dry wit is put to best use in her chapter on menopause: “Some women skip through the whole experience: their periods stop and that’s that. No erratic temperature changes, no mood swings, no brain fog, libido as good as ever. To those women, the rest of us must seem like cranky bitches.” I know how deeply affected my brain is by hormones, not only because of my dramatic monthly shifts and symptoms, but also because I experienced such a wrenchingly awful pregnancy that the memory never leaves my mind. At only six weeks, I began crying when the sun went down. At eight or nine weeks, my uterus began contracting, leaving me breathless, and I developed a painful rash. I spent much of my pregnancy deeply depressed, and I knew, even after I had seen my beautiful child, that I could never do it again. So, I expect to be one of the cranky bitches. I also want to be armed with knowledge. The trouble is, there’s conflicting data. Is it the decline in estrogen that makes women more likely to have heart attacks, strokes, dementia, osteoporosis, or is the reality more complex? Epstein reveals that studies don’t show any benefit to long-term hormone replacement therapy — that is, no reduction in these types of illnesses. However, she does offer some encouraging news: a few years of hormone therapy to ease the symptoms of menopause is unlikely to hurt you. The establishment has been back and forth on that point a few times, and, she acknowledges, who knows? It may swing the other way again. We have to muddle through with the research we’ve got at the moment. If that isn’t exactly comforting, Epstein’s writing so colorfully about the subject certainly is. I felt I had a friend guiding me through the terrifying waters of my own biology. In the meantime, I’ve got to go teach my daughter about estrogen. I sure hope she appreciates her generous stockpile of the mysterious but clearly crucial hormone.

“Your Wireless Network”: Grappling with Hormones. By Leslie Kendall Dye. Los Angeles Review of Books, August 24, 2019.