Hormonal Wars: A Brief History of Puberty Blockers

Puberty blockers are a medicine used to postpone puberty in trans children. Dr. Dana Mahr explains how they work and the transphobic rhetorics surrounding them.

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When Baltje, a 16-year-old boy, got out of his mother’s car, he knew that today’s appointment at the Gender Clinic at Utrecht University would change his life.  [1] The date was April 3, 1994, and the letterhead referred to a young doctor named Peggy Cohen-Kettenis. The main line read, “Dear Mr. Baltje, we confirm your appointment for consultation for gender reassignment therapy.

“Wow,” Baltje thought, “they’re already addressing me by my real name.”

Little did he know then that he would be the first teenager in the world whose “gender identity disorder” – as it was then defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) – would be alleviated with the help of puberty blockers until, at age 18, he finally received hormone replacement therapy optimized for his then-perceived and experienced gender. [2]

Just over 22 years earlier, chemist Masahiko Fujino was hunched over a chromatographic display in the Takeda Industries laboratory in Tokyo, indicating that he and his team had finally succeeded in synthesizing analogs of gonadotropin-releasing hormone (GnRH) agonists, making drug regulation of human sex hormones both possible and affordable. This discovery, Masahiko was certain, would revolutionize pharmacology. But the exact application of this discovery and how it could and would affect society, he and his team – as is so often the case in the field of pharmacological development – were not so sure. [3]

Medical Delineation and Regulation

The same year that Fujino and his team synthesized the first GnRH agents, U.S. President Richard Nixon signed a federal law commonly known as the “War on Cancer” . This research policy program, which reflected Cold War logic in its goals, funding, and rhetoric. This notion was accompanied by the portrayal of cancer as an “insidious adversary.” Accordingly, synthetic GnRH agents became promising candidates, particularly in combating cancers arising from hormone dysregulation. [4] It is not surprising, therefore, that early research on the precise function of GnRH agents in the human body focused on their anticarcinogenic potential for regulation. [5]

The use of political and military metaphors in medicine has a tradition dating back at least to the turn of the 20th century, when immunologists regularly distinguished between the “self” and the “other” and used the “body’s” defenses against external (and internal) enemies such as bacteria, viruses, and even tumors. [6] The use of these metaphors also had an epistemological effect. The laboratory language of leading bacteriologists of the late 19th century, such as that of Rudolf Virchow, pioneered this kind of discourse about microbes as colonizers, as foreign invaders and barbarian conquerors of the body’s borders.

Given these long-standing medical-linguistic conventions and the sociopolitical context of the early 1970s, it is not surprising that early research on the functionality of GnRH agents and their analogues focused on the anticarcinogenic potentials of hormone regulation and control. The goal was to “suppress” the carcinogenic potential of “twisted cells” that sought to compromise the functionality of their own bodies. [7] But this idea also revealed deep-seated fears of the perceived defeatism of contemporary youth cultures and their roots in American society, including the medical system. [8]

Thanks to the work of German neurologists Wolfgang Holweg and Karl Junkerman (1932), it was known by the 1970s that the pituitary gland influenced the sexual organs. However, the mechanism of this influence remained unclear. This changed in the late 1960s and 1970s when it was experimentally demonstrated that there was no direct neural influence between the brain and uterine functions, but rather a neuro-humoral mechanism. [9] This influence was primarily through the brain and the periodic release of GnRH, which stimulated follicular maturation in the ovaries and the synthesis of sex steroids. When these hormones were released at specific intervals, they maintained homeostasis and thus “normalized” the body system. However, if hormonal homeostasis was disturbed, for example by increased hormone release, this could promote the development of ovarian or breast cancer under certain circumstances. Takeda Industries’ and Fujino’s synthetic GnRH agonist served as a promising tool to mitigate and potentially treat such cancer-causing hormonal imbalances. Put simply, continuous signaling of GnRH agents desensitizes the pituitary gland, making it refractory to the trigger that stimulates further gonadotropin release. [10]

 

The promise of hormonal intervention to regulate human systems and bodies through synthetic GnRH agents that would “normalize” their function ultimately raised visions that extended beyond the individual body. Could GnRH agents also be used to regulate society?

Inclusion and Participation

With the advance of the 1970s and the rise of the counterculture in the context of many young people’s disillusionment with science and its military, financial, and patriarchal applications, a different rationale for the potential use of GnRHa agents emerged that centered on inclusion, social fairness, and participation. The feminist women’s health movement pioneered this view. [11] While the availability of the birth control pill was initially hailed by 1960s women’s health activists as a means of empowering female reproductive and socioeconomic agency, a decade of personal experience with estradiol agents revealed numerous side effects, including nausea, dizziness, headaches, and blood clots. Moreover, in the eyes of activists like Brazilian fertility doctor Elsimar Coutinho, the pill’s hoped-for liberation from patriarchal control has not been fully realized. [12] Instead of ushering in a new era of gender equality, the pill cemented the notion – especially in low-income families – that contraception is inherently a female responsibility. [13]

During the highly anticipated and globally broadcast 1974 UN World Population Conference in Bucharest, a diverse group of women activists and their allies in the scientific community called for research into the potential of GnRHa drugs for contraception to share the responsibilities and risks of contraception equally between the sexes. [14]

Following the decision of the UN Conference on Gender Equality in Contraception, various laboratories in Europe, the U.S. and Japan began studies on the fertility-inhibiting effects of GnRH drugs in men. [15] But as Vanderbilt University researcher Randy Linde and his colleagues reported in a 1981 article in the New England Journal of Medicine, GnRHa could act as a contraceptive and compromise core elements of male identity, including libido, penile functionality and testosterone-related performance. [16] Such side effects should not be tolerated in male subjects, especially since the long-term effects of the apparently reversible treatment on fertility were not yet fully known. [17] In contrast, similar effects were widely considered acceptable in female contraceptives. [18]

Canadian family physicians Pamela Verma Liao and Janet Dollin report in a 2012 essay that the blessing of being able to relinquish responsibility for contraception has led heterosexual cis men to relinquish their reproductive autonomy “by not being responsible for contraception.” [19] The toxic reactions to past research on hormonal male contraceptives also affect the present. Accordingly, there is almost no reliable quantitative data on demand for cis-male contraceptives, even though cultural conditions have changed dramatically since the 1990s. [20] Today, there is often a tacit assumption that hormonal control therapies may be too threatening to the essential male characteristics of the cis-male organism. [21]

 

The discursively generated threat to cis-male masculinity posed by GnRHa-based contraceptives ultimately leads to a darker chapter in the conceptualization and practical application of GnRHa drugs. It is directly linked to an older model of delineation and regulation: “deviant social groups” as the focus and surrogate subjects for “healthy men.” [22] To counter the charge of “making healthy men infertile,” some research laboratories shifted their GnRH research from “male organisms” to serve social control fantasies to managing “undesirable populations.” [23] A research group at the Royal Victoria Hospital in Quebec, for example, began recruiting male-female “transsexual subjects” to study the long-term effects of androgen suppression in men” [24], while others aimed to include “sexually abnormal individuals” such as “severe exhibitionists” in their studies. [25] In the right hands – the implicit rationale of some policymakers – GnRH drugs could purge the U.S. population body of the “unproductive” and the so-called “morally deviant” by depriving them of the opportunity to reproduce or engage in sexual activity. Both ethical and sociological discourse about whether such practices should be allowed continues to this day. Nonetheless, the use of GnRHa drugs to suppress fertility in transgender individuals was heavily criticized by ethicists, progressive politicians, and LGBT+ activists in the 1990s. Accordingly, its use has been largely abandoned in recent years (and rightly so).

Normalization and Affirmation of Diversity

This activism, and the associated cultural shift toward inclusivity and diversity, eventually led to a rethinking and expansion of the practical applications of GnRH resources. The sociocultural tides eventually turned in favor of marginalized groups. At the same time, the use of such agents continued well into the 2000s in the name of normalization. Just as in the individual body, it seemed necessary to maintain “homeostasis” in certain instances in society-particularly at the intersections of biology and cultural norms. An average body with average development was still considered the desirable, ideal normal.

In pediatrics, there are two relevant examples of the normalizing and diversity-affirming uses of GnRHa agents: the treatment of precocious puberty and the gender-affirming treatment of transgender and gender nonconforming youth. The normalizing uses of hormone analogues focus on the phenomenon of precocious puberty, the unusually early development of phenotypic sex characteristics in younger children. From a biological point of view, this phenomenon can hardly be called an endocrinological defect. Nevertheless, it is a social and moral truth in our societies that the puberty of eight- or nine-year-old minors deviates from the norm. Therefore, hormonal interventions in such children are considered benevolent if they help them develop their bodies and identities at a pace consistent with our societal expectations.

Diversity-affirming use of GnRH medications also results in temporary suspension of pubertal development. Modern treatment of transgender persons and gender-diverse adolescents relies on this feature of GnRH agents, not for the purpose of normalization or suppression, but to give young patients, their parents, and medical professionals more time to figure out the character and extent of an adolescent’s trans identity and individual experience of gender dysphoria. While many transgender individuals go through puberty that does not fit their identity before accessing hormone therapies, some young patients today can bypass teenage puberty with GnRH medications administered by endocrinologists and pediatricians. Similar to feminist activism for contraceptive justice, GnRH agonist-based care for adolescents seeking medical transition is understood not as a tool against a disease or deviation from a social norm, but as a medium for incorporating individual experiences into care situations. Whereas in the past, transgender individuals had to submit to a linear model of medical practice in which one’s gender had to be explored first and only then could one access health services, the new GnRH agonists nurture hopes for creative forms of transfiguration.

Establishing Epistemic Dominance

In the current sociopolitical climate of the United States and several other countries, the success of GnRHa drugs in pediatric care for transgender and gender nonconforming adolescents is becoming a political issue. Being young and transgender has become a battleground in the recent culture war between conservative and progressive social forces. Increasingly, the use of puberty blockers, so successful for many years, is discursively portrayed as a gateway drug to “harder stuff” (e.g., “performance-enhancing” testosterone therapies) for an imagined “transgender trend” among young people-especially transgender boys. GnRHa drugs, the narrative goes, would contribute to irreversible damage in many adolescents, depriving them of the possibility of normal development and future health of their bodies. This socially and epistemically conservative discourse is not only extremely infantilizing and paternalistic, denying young (trans) persons the right and ability to determine their own bodies and identities. It also aims to delegitimize the inclusive and participatory model of medicine and care.

The current culture war over minority rights is also being fought on the battlefield of epistemological truths and methods. Conservative political actors are accepting that the lives and rights of transgender youth are collateral damage in these battles. Political pundits like Ben Shapiro and Abigail Shrier aim to establish epistemic dominance in the public debate. Their tool is the narrative revival of a medical thinking that distinguishes between normal and abnormal, that can only understand hormonal intervention in the human body in the mode of social engineering. Such interventions are not interpreted in terms of self-determination. It is telling that the threatening image of chemical castration that Shapiro and Co. paint when they talk about (not to!) transgender persons 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 use of GnRH resources has always oscillated between a more delimiting and (socially) regulatory model and an identity-affirming and fairness-based model in the case of reproductive justice activism or the care of transgender youth.

From the perspective of inclusive pediatricians, such terms may seem absurd, but they (the terms) aim to change cultural discourse and, secondarily, medical practice. The creation of narratives such as “transgender trend” or “rapid onset gender dysphoria” does not reflect the realities of trans people’s lives, but instead leads to more denial of much-needed health care services by the day. Pediatricians are not immune to such political propaganda, but in a political climate like the current one, they are challenged more than ever to acquire reflexive knowledge to meet the challenges facing their young patients. In addition, they should also listen to and be sensitive to the diverse knowledge about gender and the body that is being generated by transgender activists and academic groups.

The regulatory impact of GnRH agents on society depends heavily on their socio-epistemic and discursive framing, which is shaped by political biases. From a conservative epistemological perspective, these pharmaceutical agents are often understood in terms of social engineering and regulatory control. This understanding seems to be prevalent in conservative media and exclusive radical feminist transgender circles, as highlighted by the recent example of the unhinged rantings of erotic film actress and activist Lily Cade. In conspiratorial circles, the use of puberty blockers is presented as part of the (imagined!) “great detachment.” By emasculating and de-feminizing Western youth, “the elites” would pave the way for a “new world order.” Yet even in less radical conservative imaginaries, GnRH agents evoke visions of social control and regulation, as evidenced by their classification as a means to address the deviant behavior of sex offenders. The cognitive dissonance between the classification of both uses as “dangerous” and “desirable” is significant for the distribution of an individual’s imagined value in society.

Diversity-affirming uses of GnRH drugs stand in stark contrast to this notion. These ideas are not about controlling people’s bodies, but about enabling individual agency, especially in relation to gendered roles in society. The possibility of giving young people seeking to transition control over their own bodies through a simple pharmaceutical agent fundamentally contradicts the narrative of social regulation. This leads to an incommensurability and reinterpretation of the use of puberty blockers in the conservative sociotechnical paradigm as presented by conservative alarmists. The simple act of self-efficacy by a young person is thus elevated to a fundamental affront.

About the Author

Dana Mahr is a Maître-Assistante at the University of Geneva, Switzerland. Her research focuses on how marginalized social groups understand the normative aspects of science, technology, and medicine from a socio-historical and epistemological perspective. As a transgender person, she is also committed to improving health care and social inclusion of LGBTQIA+ persons in Europe.

Sources

[1]  P. T. Cohen-Kettenis und S. H. van Goozen, “Pubertal Delay as an Aid in Diagnosis and Treatment of a Transsexual Adolescent”, European Child & Adolescent Psychiatry 7, no. 4 (Dezember 1998): 246–48., https://doi.org/10.1007/s007870050073.

[2] Cohen-Kettenis und van Goozen, “Pubertal Delay”.

[3]  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 (März 1974): 314–19, https://doi.org/10.1021/jm00249a012.

[4] Petra Dickmann, Biosecurity: Biomedizinisches Wissen zwischen Sicherheit und Gefährdung (transcript Verlag, 2014). https://doi.org/10.14361/transcript.9783839419205.

[5] Y. Koch et al., “Suppression of Gonadotropin Secretion and Prevention of Ovulation in the Rat by Antiserum to Synthetic Gonadotropin-Releasing Hormone”, Biochemical and Biophysical Research Communications 55, no. 3 (Dezember 10, 1973): 623-29, https://doi.org/10.1016/0006-291X(73)91189-3; I. Huhtaniemi, H. Nikula, and S. Rannikko, “Treatment of Prostatic Cancer with a Gonadotropin-Releasing Hormone Agonist Analog: Acute and Long Term Effects on Endocrine Functions of Testis Tissue”, The Journal of Clinical Endocrinology and Metabolism 61, no. 4 (Oktober 1985): 698-704, https://doi.org/10.1210/jcem-61-4-698; A. Manni et al., “Treatment of Breast Cancer with Gonadotropin-Releasing Hormone,” Endocrine Reviews 7, no. 1 (February 1986): 89-94, https://doi.org/10.1210/edrv-7-1-89; M. A. Blankenstein, M. S. Henkelman, and J. G. Klijn, “Direct Inhibitory Effect of a Luteinizing Hormone-Releasing Hormone Agonist on MCF-7 Human Breast Cancer Cells,” European Journal of Cancer & Clinical Oncology 21, no. 12 (December 1985): 1493–99, https://doi.org/10.1016/0277-5379(85)90244-5.

[6] Philipp Sarasin, “Die Visualisierung Des Feindes. Über Metaphorische Technologien Der Frühen Bakteriologie,” Geschichte Und Gesellschaft 30, no. 2 (2004): 250-76.

[7]  Koch et al., “Unterdrückung der Gonadotropinsekretion”.

[8] Mahr, The Knowledge of Experience.

[9]  Y. Koch et al., “Resistance to Enzymic Degradation of LH-RH Analogues Possessing Increased Biological Activity”, Biochemical and Biophysical Research Communications 74, no. 2 (January 24, 1977): 488–91, https://doi.org/10.1016/0006-291X(77)90330-8.

[10]  R. Felberbaum und U. Karck, “GnRH-Analoga in der Gynäkologie: Agonisten und Antagonisten”, Geburtshilfe und Frauenheilkunde 57, Nr. 10 (Juni 17, 2008): 539–44., https://doi.org/10.1055/s-2007-1023133

[11] Mahr, The Knowledge of Experience.

[12] Andy Extance, “What Happened to the Male Contraceptive Pill?”, The Guardian, 23. Juli 2016, http://www.theguardian.com/society/2016/jul/23/what-happened-to-the-male-contraceptive-pill.

[13] C. Djerassi, “Die bittere Pille”, Science 245, no. 4916 (Juli 28, 1989): 356-61; C. Ezzell, “Hormone-Blockers May Yield Male Pill'”, Science News, 1991, 407-407; Sam Kean, “Reinventing the Pill: Männliche Geburtenkontrolle”, Science 338, Nr. 6105 (2012): 318-20.

[14] W. P. Mauldin et al., “A report about Bucharestt. The World Population Conference and the Population Tribune, August 1974”, Studies in Family Planning 5, Nr. 12 (Dezember 1974): 357-95.

[15] C. Bergquist, S. J. Nillius und L. Wide, “Intranasal Gonadotropin-Releasing Hormone Agonist as a Contraceptive Agent,” The Lancet 2, no. 8136 (August 4, 1979): 215-17, https://doi.org/10.1016/S0140-6736(79)90235-6; M. Davis-daSilva und K. Wallen, “Suppression of Male Rhesus Testicular Function and Sexual Behavior by a Gonadotropin-Releasing-Hormone Agonist,” Physiology & Behavior 45, no. 5 (Mai 1989): 963–68, https://doi.org/10.1016/0031-9384(89)90222-9.
[16] R. Linde et al., “Reversible Inhibition of Testicular Steroidogenesis and Spermatogenesis by a Potent Gonadotropin-Releasing Hormone Agonist in Normal Men: An Approach toward the Development of a Male Contraceptive,” The New England Journal of Medicine 305, no. 12 (September 17, 1981): 663–67, https://doi.org/10.1056/NEJM198109173051203.

[17] Linde et al., “Reversible Inhibition”.

[18] Djerassi, “Die bittere Pille”.

 

[19] Pamela Verma Liao und Janet Dollin, “Half a Century of the Oral Contraceptive Pill: Historical Review and View to the Future”, Canadian Family Physician Medecin de Famille Canadien 58, no. 12 (Dezember 2012): e757-60.

[20] Liao und Dollin, “Ein halbes Jahrhundert orale Verhütungspille”.

[21] Extance, “Was ist aus der Pille für den Mann geworden?”

[22] Mahr, The Knowledge of Experience.

[23] Mahr, The Knowledge of Experience.

[24] G. Tolis et al., “Suppression of Androgen Production by D-Tryptophan-6-Luteinizing Hormone-Releasing Hormone in Man”, The Journal of Clinical Investigation 68, no. 3 (September 1981): 819–22, https://doi.org/10.1172/JCI110320.

[25]  L. Rousseau et al., “Effect of Combined Androgen Blockade with an LHRH Agonist and Flutamide in One Severe Case of Male Exhibitionism,” Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 35, no. 4 (Mai 1990): 338–41, https://doi.org/10.1177/070674379003500412.

[26] Carl Elliott, Better Than Well(W. W. Norton & Company, 2004).


[27] 
Christopher James Ryan, “Is It Really Ethical to Prescribe Antiandrogens to Sex Offenders to Decrease Their Risk of Recidivism?”, in Neurointerventions and the Law (Oxford University Press, 2020), 270-92, https://doi.org/10.1093/oso/9780190651145.003.0012.

[28] Steven Epstein, Inclusion: The Politics of Difference in Medical Research (University of Chicago Press, 2008).

[29] D. Mahr und L. Prüll, “Körperliche Selbstermächtigung Aus Dem 3D Drucker? Feministische Kulturen Als ‘Parallelwelten’ und Der Kampf Um Gesellschaftliche Teilhabe Seit 1970,” Systematische Un/Ordnung-Zum Verhältnis von Digitaler Technologie Und Gesellschaftlicher Emanzipation, Münster: Unrast, 2017, 161-90.

[30] Florence Ashley, “Thinking an Ethics of Gender Exploration: Against Delaying Transition for Transgender and Gender Creative Youth,” Clinical Child Psychology and Psychiatry 24, no. 2 (April 2019): 223-36, https://doi.org/10.1177/1359104519836462.
 
[31] Mahr, The Knowledge of Experience.
 
[32] Abigail Shrier, Irreversible Damage(Simon and Schuster, 2020).

[33] Shrier, Irreversible Damage

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