Hormonal Wars: A Brief Regulatory History of Puberty Blockers

December 22, 2021

Hormonal Wars

A Brief Regulatory History of Puberty Blockers

By Dana Mahr

Art by @sofftpunk

As Baltje, a 16-year-old boy, got out of his mother’s car, he knew that today’s appointment at Utrecht University’s gender clinic would change his life. This morning, much to his father’s displeasure, he had not gone to school. Again, and again his eyes slid to the letter in his hand, even during their ride. The date was April 3, 1994, and the letterhead referred to a young doctor named Peggy Cohen-Kettenis. The most important line read: “Dear Baltje, we confirm your appointment regarding consultations for gender reassignment therapies.”

“Wow,” thought Baltje, “they already refer to me with the right name.”

Together with his mother, he walked the few steps from the parking lot to the clinic. Little did he know at the time that he would be the world’s first adolescent whose “gender identity disorder”—as defined by the The Diagnostic and Statistical Manual of Mental Disorders (DSM) at the time—was to be alleviated with the help of puberty blockers until eventually, at age 18, by a hormone replacement therapy optimized for his then perceived and experienced gender.1

A little more than 22 years earlier, and well over five thousand miles away in the Takeda Industries laboratory in Tokyo, the chemist Masahiko Fujino was bending over a chromatographic display indicating that he and his team had finally succeeded in synthesizing analogs of gonadotropin-releasing hormone (GnRH) agonists, thus making drug-induced regulation of human sex hormones both possible and affordable. This discovery, Masahiko was sure, would revolutionize pharmacology. But the exact application for this discovery and how it could and would influence society, he and his team were—as so often in the field of pharmacological development—not so sure.2 Without knowing, both Baltje and Fujino would become actors in the reshaping of medical epistemology that is more inclusive of personal experience and a source of both scientific knowledge production and health related participatory decision-making in terms of policy making, drug implementation, and study designs.

By applying a feminist perspective to the history of GnRH agonists, this essay will disentangle some of the complex transformations in medical research and practice that have led to both contentment with and aversion from the medical system in the current sociocultural climate. On the one hand, medical institutions seem to strive to become more inclusive and diverse, but on the other hand, these activities are framed by some currently prominent societal actors as proof that science is falling victim to “identity politics.” In this climate, it is important to keep in mind that drugs, their agents, and their use are not only medical or pharmaceutical entities but also sociocultural artifacts.3 Accordingly, I will use GnRH agonists as a prism to highlight the underlying politics and shifts in epistemology that have led to the contemporary disparities in trust toward the institution of medicine. I will trace the transformations of such pharmaceutical agents, initially understood as weapons in the “war on cancer,” into tools allowing transgender and gender nonconforming adolescents to explore their identity without experiencing hormonal changes that might be detrimental to their mental health. I will identify two modes of epistemic and social significance of puberty blockers: (1) GnRH agonist as a tool for delimitation and regulation, and (2) GnRH agonist as one element (among many) in making medical care more inclusive and participative, integrating the experiential knowledge of those who are subjected to it. Both modes represent specific assemblages of scientific values, social norms, ideals, fears, and medical practices, signifying specific sociohistorical climates and positions.

Medical Delimitation and Regulation

In the same year as Fujino and his team first synthesized GnRH agents, US president Richard Nixon signed a federal law known commonly as the “war on cancer,” which aims to strengthen the National Cancer Institute to fund cancer studies.4 This research policy program, which reflected the logic of the Cold War in its objectives, funding, and rhetoric, postulated a seamless pipeline of knowledge-transfer from the laboratory to the customer/patient, thus signifying the dominance of capitalism.5 This notion paralleled the portrayal of cancer as an “insidious adversary.” Yet, as clarified in a 2014 Lancet article, this characterization also had epistemic consequences including a narrative of “targeted” “strikes” against cancer via pharmaceutical agents.6 Accordingly, synthetic GnRH agents became promising candidates, especially in combating cancers arising out of hormone dysregulation.7 It is therefore not surprising that early research into the precise function of GnRH agents in the human body focused on their anti-carcinogenic potential for regulation.8

The “war on cancer” reflected the logic of the Cold War in its objectives, funding, and rhetoric. It postulated a seamless pipeline of knowledge-transfer from the laboratory to the customer/patient, thus signifying the dominance of capitalism.

The use of political and military metaphors in medicine is a tradition dating back at least to the turn of the 20th century when immunologists regularly distinguished between “Self” versus “Other,” and the “body’s own” defenses armed against external (and internal) enemies such as bacteria, viruses, or even tumors.9 The use of these metaphors also had an epistemological impact. In medical discourse, the use of drugs or the ingestion of vitamins was, for example, compared to the enlistment of auxiliary forces for one’s own immune force. Bodily realities were conceptualized by clear-cut boundaries between good/bad and inside/outside rather than being understood as a system of interfaces across diffuse boundaries, interacting with and in its environment.10 The laboratory language of leading bacteriologists in the late 19th century, like that of Rudolf Virchow, pioneered this kind of discourse about microbes as colonizers, as foreign invaders, and barbaric conquerors of the body’s boundaries. Such epistemic metaphors for describing the interaction of human bodies with their environment are not neutral but reflect the cultural climate of their time. It becomes clear, for example, when Virchow depicted the relationship between the body and microorganisms as a colonial relationship by describing bacteria as foreigners invading the organism, such as the “Sudanese.”11 Hereby, as the historian Philip Sarasin states, epistemic metaphors invoke not only colonial thinking but also embed racist prejudices in biomedical knowledge. In a narrative reversal of power relations, the pure, good white population of Europe is equated with the cells of a healthy body endangered by the influence of destructive foreigners, those respective microorganisms. The universal remedy against the civilizational danger by (brown) foreigners as well as the threat of infectious diseases are ultimately framed as the same: a strengthening of the internal defense forces. This thinking about the human body and the civil/social body extends far into the 20th century.12 Thus, a militarist and delimitative lingo prevails in fields like oncology in metaphorical language and thus epistemic practice even today. When speaking about “cancer warfare” scientists and doctors are not making a statement about the realities of bodily processes, but rather they are reaffirming a specific way of thinking about cancer, thus taking away the possibility of thinking about cancer treatments from a different angle.13

Given both these long-standing, medico-linguistic conventions and the sociopolitical context of the early 1970s, it is not surprising that early research into the functionality of GnRH agents and their analogs focused on the anti-carcinogenic potentials of hormone regulation and warfare. The aim was to “suppress” the cancerous potential of the twisted cells that sought to endanger an individual body’s functionality.14 Yet, this thought also revealed deep-seated fears of the supposed militarism of contemporary youth cultures and the roots of these fears in American society, including the medical system. Unlike the enemies coming from outside, however, neither politicians nor doctors could simply suppress these actors (both cancer cells and countercultural, white youths) with open violence, as after all they were not the “others.” Therefore, a solution was sought in contemporary social regulatory theories (modeled after biological theories), substituting direct influences with systemic ones.

Due to the works of German neurologists Walter Hohlweg and Karl Junkerman (1932), by the 1970s it was known that the pituitary gland influenced sexual organs. However, the mechanism of this influence remained unclear. This changed in the late 1960s and 1970s, when it was experimentally shown that there was no direct neuronal influence between brain and uterine functions but rather a neurohumoral mechanism.15 This influence was affected primarily through the brain and via periodic releases of GnRH that stimulated follicular maturation in the ovaries and sex steroid synthesis. When released in specific intervals, these hormones maintained homeostasis and thus “normalized” the bodily system. Yet, if the hormonal homeostasis was disturbed—for example, due to an increased hormonal distribution—it could, under specific circumstances, promote the development of ovarian or breast cancer. Takeda Industries and Fujino’s synthetic GnRH agonist served as a promising tool for the mitigation of and possible therapy against such cancer-inducing hormonal imbalances. In simple terms, continuous signalling by the GnRH agents on the pituitary gland desensitizes it, thus making it refractory to the trigger that stimulates further gonadotropin release. This was shown, among others, by the gynecologists Robert Felberbaum and Uwe Karck from the University Hospital Lübeck, who attributed the desensitization to a decoupling of the receptor from the intracellular signal transduction pathway triggered by GnRH agonist.16

The promise of hormonal intervention to regulate human systems and bodies via synthetic GnRH agents was meant to “normalize” their function, and this promise ultimately evoked visions beyond individual bodies. Could GnRH agents be used to regulate society? Additionally, this vision was recombined with the still prevalent good/bad and inside/outside discourse. Yet, this parallelled a different way of sense-making towards medicine, one that arose from a socially and epistemically infused by feminist and countercultural values—revisiting the use of GnRH agents from the perspective of those who were initially envisioned as the subjects of regulatory social control by culturally (and epistemically) conservative policy makers.

Inclusion and Participation

With the advance of the 1970s and the rise of the counterculture in the context of the disillusion of many young people from the sciences and their military, financial, and patriarchal applications, another rationale emerged for the potential use of GnRH agents, centering inclusion, social fairness, and participation. The feminist women’s health movement pioneered this perspective.17 While the availability of the birth control pill was initially praised by women’s health activists of the 1960s as a means for enhancing female reproductive and socioeconomic agency, a decade of personal experience with estradiol agents identified numerous side effects including nausea, dizziness, headaches, and blood clots. Furthermore, the anticipated liberation from patriarchal control via the pill did not, in the eyes of activists like the Brazilian fertility doctor, Elsimar Coutinho, fully materialize.18 Rather than bringing forth a new dawn for gender equality, it cemented—especially in low-income families—the notion that contraception is inherently a female responsibility.19

During the highly anticipated and globally broadcast UN World Population Conference 1974 in Bucharest, a diverse group of female activists and their allies in the scientific community demanded that the potential of GnRH agents for contraceptive care should be explored as a means of equally distributing responsibility and risks of contraception between the sexes.20 Like other activities of contemporary women’s health collectives (for example, menstrual cycle studies or self-help courses), the objective of the Bucharest women’s contraceptive equality groups was both political and epistemic in nature. They were united by the vision of broadening the epistemic toolbox of medical science and practice by integrating their own experiential perspectives, thus mitigating the male-dominant bias of medical institutions that feigned neutrality of values.21 These practical activities ultimately led to a systematization within the emerging field of feminist epistemology. The contextual empiricism of Helen Longino, for example, grounds its epistemic foundations in values like “applicability to human needs,” which can be interpreted as a direct recall to 1970s practical activism.22

United by the vision of broadening the epistemic toolbox of medical science and practice by integrating experiential perspectives, the activism for contraceptive care equality ultimately led to a systematization within the emerging field of feminist epistemology.

Following the UN conference’s resolution to equalize contraceptive care, various laboratories in Europe, the US, and Japan began studies on the antifertility effects of GnRH agents in male organisms.23 Yet, as Vanderbilt University researcher Randy Linde and colleagues reported in a 1981 New England Journal of Medicine article, GnRH agonists could function as contraception and endanger core elements of the masculine identity, including libido, penile functionality, and testosterone-related performance. Such side-effects should not be tolerated for male subjects, especially since the long-term effects of the apparently reversible treatment on fertility were not yet fully understood.24 In contrast, similar effects in women’s contraceptives were widely regarded as acceptable.25 As Nelly Oudshoorn argues in an analysis of male contraception in the 1980s and 1990s, there simply was no market in the West for hormonal male contraceptives.26

The Canadian family physicians Pamela Verma Liao and Janet Dollin report in a paper from 2012 that the boon of forfeiting the burden of responsibility of contraception led to a situation where heterosexual cis men ceded reproductive autonomy “by not being responsible for contraception.”27 Toxic reactions towards past research into hormonal male contraceptives also affect the present. Accordingly, there are almost no reliable quantitative data on the demand for cis-male contraception although the cultural conditions have drastically shifted since the 1990s. Today, it is often tacitly assumed that hormonal control therapies may be too threatening for the essential masculine characteristics of the cis-male organism.28 Such an archaic image of masculinity in medicine does not take seriously the complexity of many men’s identities in the 21st century, especially since many men would like to take on more responsibilities with regards to contraception. Both the hype around Rachel Weiss’s invention of COSO (an ultrasound-based reversible male contraceptive device) as well as experiential reports of younger men support this.29 Thus, the complexities of men’s identities and positions towards contraception are becoming the next frontier for intersectional feminist activities in the 21st century.

The discursively generated threat of GnRH agonist–based contraceptives to cis men’s masculinity ultimately leads to a darker chapter in the conceptualization and practical application of GnRH agents directly tied to an older model of demarcation and regulation: “deviant social groups” as focus and surrogate subjects for “healthy men.” To mitigate accusations of “making healthy men sterile,” some research laboratories shifted their GnRH research from “male organisms” to serve social control fantasies towards managing “undesirable populations.”30 A research group from the Royal Victoria Hospital in Quebec, for example, began to recruit male-to-female “transsexual subjects” for the study of long-term effects of androgen suppression in men,31 while others aimed to include sexually “deviant” individuals like “severe exhibitionists” into their studies.32 In the right hands—according to the implicit rationale of some policy makers—GnRH agents could cleanse the US population of the “unproductive” and so-called “morally deviant” by denying them the possibility to procreate or be sexually active.33 The discourse—both ethical and sociological—of whether such practices should be allowed prevails until today.34 Yet, the utilization of GnRH agents in suppressing the fertility of transgender individuals became highly criticized by ethicists, progressive policy makers, and LGBT+ activists in the 1990s. Accordingly (and rightly so), their use has been widely abandoned in recent years.35

Normalization and Diversity Affirmation

Such activism and the associated cultural shift towards inclusivity and diversity finally led to a rethinking and expansion of GnRH agents’ practical uses. Sociocultural tides eventually turned in favor of marginalized groups. Yet, in parallel, the uses of such agents on behalf of normalization prevailed far into the 2000s. Just as within an individual body, it seemed also necessary to maintain the “homeostasis” of society—in certain cases—especially at the interfaces of biology and cultural norms. An average body with an average development was still regarded as the desirable, ideal normal.36

In pediatrics, there are two relevant examples of normalizing and diversity affirming uses of GnRH agents: respectively, the treatment of precocious puberty, and gender affirming care for transgender and gender diverse adolescents. The normalizing uses of hormonal analogues center the phenomenon of precocious puberty, the unusually early development of phenotypical sex characteristics in younger children. From a biological perspective, this phenomenon can hardly be framed as an endocrinological defect; it is nonetheless a social and moral truth in our societies that puberty in eight- or nine-year-olds deviates from the norm. Thus, hormonal intervention for such children is considered benevolent because it helps them to develop their bodies and identities at a pace that aligns with our societal expectations. While the endocrinological effects on development have been clinically proven as fully reversible after discontinuation, the pediatric use of GnRH agonist–based drugs like Takeda Industries’s leuprorelin acetate—as the compound first observed by Fujino in 1972—has been recently criticized by patient groups. On the online patient forum PatientsLikeMe, Sharissa Derricot, who underwent treatment for several years in childhood, described persistent side effects later in life including osteoporosis and fibromyalgia.37 In parallel, the drug has also been prescribed for off-label uses: for example, to enhance the growth of children with below-average height by pediatricians since the 2000s. This has led to over ten thousand reports of adverse events to the FDA in recent years, thus raising questions about the individual price of a normalized puberty onset.38

The diversity affirming use of GnRH agents likewise centers a transient suspension of pubertal development. Modern care for transgender and gender diverse adolescents relies on the puberty-blocking effects of GnRH agents, not with the goal of normalization (nor of oppression) in mind but to grant young patients, their parents, and medical professionals more time to figure out the character and scope of a youth’s trans identity and their individual experience of gender dysphoria. While many transgender individuals live through a puberty at odds with their identity before gaining access to hormonal therapies, some young patients today are enabled to circumvent puberty in their teenage years with GnRH agents administered by endocrinologists and pediatricians. Like the feminist activism for contraceptive fairness in Budapest, GnRH agonist–based care for adolescents seeking medical transition is not framed as an instrument against a disease or against deviations from a social norm, but as a medium for the inclusion of individual experience in care situations. While transgender individuals had to submit themselves in the past to a linear model of medical practice, in which they had to first explore their gender and only then were they granted access to health care services, new uses of GnRH agonist foster hope for creative forms of transfiguration.39

The benefits and humanity of such an approach became apparent for the first time when Peggy Cohen-Kettenis and her colleague Stephanie van Goozen reported their impressions of and experiences with GnRH agonist treatment in Baltje, the young transgender man, in the journal European Child & Adolescent Psychiatry in 1998. Together with seeing psychotherapists, gender specialists, and endocrinologists, this therapy enabled him to have a psychologically healthy transgender maturation experience, which transformed his feeling of gender dysphoria ultimately into gender euphoria.40 Following this example, over the course of the 2000s the use of GnRH agents became a standard for gender affirming care for transgender and gender diverse youth.41

Manufacturing Epistemic Dominance

In the current sociopolitical climate of the US and various other countries, the success of GnRH agents in pediatric care for transgender and gender diverse adolescents has become politicized. Being young and transgender has become a battleground for the latest cultural war between conservative and progressive societal forces.42 Increasingly, the use of puberty-blocking drugs, which has been successful for many years, is being discursively turned into a gateway to “harder things” (for example, “performance enhancing” testosterone therapies) for an imagined “transgender trend” among young people—especially transgender boys.43 GnRH agents, the narrative goes, would contribute to irreversible damage in many adolescents and deprive them of the possibility of a normal development and future health of their bodies.44 Not only is this socially and epistemically conservative discourse extremely infantilizing and paternalistic—it denies young trans individuals the right and ability to determine their bodies and identity for themselves—but it also aims to delegitimize the inclusive and participative model of medicine and care.

Likewise, the current cultural struggle over the rights of minorities is fought on the battlefield of epistemological “truths” and methods. Conservative political actors thereby accept the lives and rights of transgender adolescents as collateral damage in these struggles. Political pundits, like Ben Shapiro or Abigail Shrier, aim to manufacture epistemic dominance in public discussion. Their tool is the narrative revival of a medical thinking that distinguishes between normal and abnormal, that can only understand the hormonal intervention in human bodies in the mode of social engineering. Such interventions are not interpreted in the mode of self-determination. It is significant that the threatening image of chemical castration drawn by Shapiro and others when talking about (not with!) transgender individuals turns into approval in the case of sex offenders. This is particularly easy and equally dangerous, because as I have shown in the brief historical outline of this essay, the uses of GnRH agents have always oscillated between a more delimiting, socially regulatory model and an identity affirming, fairness-based model, as shown in the cases of reproductive justice activism and care for transgender youth.

The regulatory impact of GnRH agents on society strongly depends on their socio-epistemic and discursive framing informed by political preconceptions.

From the perspective of inclusive pediatric practitioners, such notions may seem absurd, but they (the notions) are focused on shifting the cultural discourse, and by extension, altering established medical practice. The invention of narratives about a “transgender trend” or “rapid onset gender dysphoria” does not reflect the reality of trans people’s lives, but it is leading day by day to more denial of much-needed healthcare services. Pediatricians are not immune to such political propaganda, yet in the current political climate, they are challenged more than ever to acquire reflexive knowledge for navigating through the challenges of their young patients. Additionally, they also should listen and be sensitive to the diverse range of knowledge on gender and the body generated by transgender activists and academic groups.

The regulatory impact of GnRH agents on society strongly depends on their socio-epistemic and discursive framing informed by political preconceptions. From a conservative epistemological angle these pharmaceutical agents are oftentimes understood in terms of social engineering and regulatory control. This understanding seems to predominate in conservative media and transgender exclusive radical feminist circles, as most recently the example of the unhinged tirades of the adult film actress and activist Lily Cade underscore. In conspiratory mindsets the use of puberty blockers is framed as part of the (imaginary!) “great replacement.” By demasculinizing and defeminizing western adolescents “the elites” would pave the way for a “new world order.” Yet also in less radical conservative imaginations GnRH agents evoke visions of social control and regulation, as their framing as a remedy for the deviant behavior of sexual predators shows. The cognitive dissonance between the framing of both uses as “dangerous” and “desirable” is significant for the distribution of an individual’s imagined worth in society.

The diversity affirming use of GnRH agents stands in stark contrast to this notion. These ideas are not about controlling people’s bodies but about enabling individual agency, especially over gender-specific roles in society. The possibility of using a simple pharmaceutical agent to give young people who want to transition control over their own bodies fundamentally contradicts the social regulatory narrative. This leads to incommensurability and reframing of the use of puberty blockers in the conservative social-technical paradigm, as exemplified by conservative alarmist ideas. The simple act of self-efficacy of a young person is thus elevated to a fundamental affront.

Beyond these sociopolitical and epistemic positioning, however, the discourse around puberty blockers also offers new opportunities for the social studies of science and feminist scholars. In the discussion about the social consequences and role of GnRH agents, a constitutive element often remains underlit: the experiential dimension of those who decide to temporarily inhibit their puberty with these agents. The experiences of transgender and gender nonconforming adolescents need to be studied in a qualitative fashion; their voices need to be heard (and not only interpreted); and ultimately their knowledge must be at the center of scientific knowledge production and participatory decision-making. A systematization of these unique data is a desideratum which could lead once more to a broadening of the epistemic toolbox of science itself.

Dana Mahr is maître-assistante (assistant professor) at the University of Geneva, Switzerland. Her research centers on how marginalized social groups make sense of the normative aspects of science, technology, and medicine from a sociohistorical and epistemological angle. As a transgender person she also advocates for the betterment of healthcare services for and societal integration of LGBTQIA+ individuals in Europe.


  1. The patient was anonymized and referred to as B. Here I name him “Baltje” for narrative purposes. See  P. T. Cohen-Kettenis and S. H. van Goozen, “Pubertal Delay as an Aid in Diagnosis and Treatment of a Transsexual Adolescent,” European Child & Adolescent Psychiatry 7, no. 4 (December 1998): 246–48., ​​https://doi.org/10.1007/s007870050073.
  2. M. Fujino et al., “Syntheses and Biological Activities of Analogs of Luteinizing Hormone Releasing Hormone (LH-RH),” Biochemical and Biophysical Research Communications 49, no. 3 (November 1, 1972): 698–705, https://doi.org/10.1016/0006-291X(72)90467-6; W. Arnold et al., “Synthesis and Biological Activity of Some Analogs of the Gonadotropin Releasing Hormone,” Journal of Medicinal Chemistry 17, no. 3 (March 1974): 314–19, https://doi.org/10.1021/jm00249a012.
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