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Oestrogen and Time

Oestrogen and Time

 

Viviane Quirke, Oxford Brookes

 

Oestrogen in many ways is the original ‘matter’ (from the Latin ‘mater’, i.e. ‘mother’).1 Secreted by the ovaries, it promotes the development and maintenance of female characteristics in animals, and controls their reproductive cycle. Hence it was long considered to embody and define femininity, i.e. to be the quintessential ‘female material’. Now it is better understood to be present in both males and females, but in different quantities at different stages of their development.2  Although not a ‘biomaterial’ as the term is currently understood, oestrogen is nevertheless a material in the scientific and technical sense of the word.3  Extracted at first from ovaries, and subsequently from other biological material such as urine or plants, later on part-synthesised or synthesised from non-biological as well as biological material, it has been manipulated and modified into a research tool for investigating physiological processes in the laboratory, and made into ‘things’ (mostly drugs) in the factory. Like other materials, it has at once resisted, and been amenable to physical intervention. Owing to the complexity of its physiological action in the body, it has also resisted before eventually yielding to scientific knowledge and understanding.

Oestrogen is therefore involved in three main, intertwined types of temporality. First, it plays an important part in the lifecycle of female/male humans. Second, it has its own ‘lifetime’, for it has an ancient evolutionary history,4 and what is known about it, what has been made from it, has depended on the historical context in which it has been deployed. Finally, with the discovery that the oestrogen content of certain plastics has been leaching into the environment, especially in water, a third kind of temporality has come to the fore: one of persistence, endurance, inheritance and legacy. As such, oestrogen has shown itself to be not just a passive material, the object of human intervention, but to be an agent of change – across both time and space, from conception to old age, and from a micro, molecular level, to a macro, environmental level.

The lifecycle of females/males

Oestrogen as a term is commonly used to refer to any of the female sex hormones: oestrone, oestradiol, oestriol, and oestestrol, the latter produced only during pregnancy. It is therefore a group of hormones, which are now known to be either endogenous (occurring naturally in the body) or exogenous, i.e. with a similar effect to endogenous oestrogen, but produced outside the body (either naturally and present in foods like soy, or artificially and found in industrial compounds such as bisphenol A or phthalates in some plastics, which are therefore classed as ‘endocrine disruptors’).5

Oestrogen, whether endogenous or exogenous, whether natural or synthetic, plays a major part in sex differentiation after conception, producing secondary sex characteristics such as the distribution of body hair and fat. At the onset of puberty, it contributes to pubertal development in males as well as driving feminization in females.6  It then regulates the female reproductive system, including the female menstrual cycle and pregnancy (see Figure 1).

 

Figure 1: Artwork by Susan Lockhart showing the stages and relationship between events during a female menstrual cycle.7

Later in the human lifecycle the quantities of oestrogen present in women’s bodies become depleted, leading to the menopause, while in men increasing levels of oestrogen relative to testosterone may lead to diabetes and certain forms of cancer (including prostate cancer), thus participating in the human ageing process.8 Nevertheless, adequate levels of oestrogen have been shown to be important for the health of adult males. In 2013, a study in the New England Journal of Medicine suggested that oestradiol as well as testosterone were needed to maintain healthy amounts of fat, especially abdominal fat, as well as to maintain libido and sexual function.9

However, it was not always known to be the case, and the issue still generates controversy today.10 Oestrogen’s first identity, as the ‘female principle’, an expression used in 1929 by Robert Frank, a gynaecologist from Mount Sinai Hospital in New York,11 reflected the dualistic conception of sex and gender that was dominant at the time. Oestrogen’s existence as a ‘material’, subject to human intervention and understanding, has since then revealed its many roles and produced the multiple identities that characterise it today, as a research object, diagnostic tool, contraceptive pill, hormone replacement therapy (HRT), treatment for disorders of the endocrine system and hormone-dependent cancers, and gender-affirming therapy for transgender females.12  In what follows, I outline this ‘life trajectory’ of oestrogen from simple to complex material, involved in a variety of temporalities.

The life trajectory and multiple identities of oestrogen

Although oestrogen has been found to be present in invertebrates as well as vertebrates, suggesting that it has played a significant part in the evolution of life on earth,13 and the idea that ovaries were in some way linked to female sexuality goes as far back as Aristotle,14 our story of oestrogen as a material truly begins in the late nineteenth century. In 1889, the French physiologist Charles-Edouard Brown-Séquard reported to his colleagues  at the Société de Biologie in Paris that a midwife had used the filtered juice of guinea-pig ovaries to treat women suffering from a range of illnesses, including ‘hysteria, various uterine affections, and debility due to old age’.15 In an article written in the Lancet in the same year, he also reported on his self-experimentation with injections of crushed animal testicles diluted in water, which he argued produced in him, at 72 years of age, ‘renewed vigour and mental clarity’.16 Although at the time the substance was mockingly referred to as the ‘Brown-Séquard Elixir’ and his work was described as bordering on quackery,17 it revived interest in what was now called ‘organotherapy’, treatments using extracts from animal organs, including ovarian extracts, which were sometimes used to treat hot flushes.18 By then, the surgical removal of ovaries (oophorectomy) to treat a number of ‘women’s problems’ was also becoming commonplace. In 1896, the Scottish physician George (later Sir George) Thomas Beatson reported on successful cases of treating premenopausal breast cancer sufferers with oophorectomy, after which it became a standard treatment for advanced breast cancer.19 In 1906, ovarian extracts were shown to induce oestrus (the fertile phase in females’ reproductive cycle). However, oestrogen did not acquire its name until the 1920s, when it was isolated, purified and chemically characterised as a ‘steroid’ (containing a nucleus of four fused rings and 17 carbon atoms).

The chemical characterisation of oestrogen opened the way to its manipulation and processing first into artefacts which mimicked its effects in the body, and were used to treat oestrogen deficient states, including menstrual disorders and the symptoms of the menopause. An early example was Premarin. Extracted from the urine of pregnant mares, which was more abundant and more easily available than that of pregnant women, it was launched in 1941, and is still in use today.20 Synthetic analogues of oestrogen also made their appearance at that time, such as stilboestrol (1938, see Figure 2). It was used to prevent miscarriages, and became infamous not only for causing a rare form of vaginal cancer in the daughters of the women who had been prescribed the drug, but also for being given in 1952 to the mathematician and code breaker Alan Turing as a treatment for homosexuality.21

Figure 2: ‘A triumph of synthesis: stilboestrol, a synthetic oestrogen’, Burroughs Wellcome & Co., London.22

The myriad drugs that followed in the wake these early beginnings of oestrogen as a material included Enovid, the first ‘combined pill’ containing both oestrogen and progestin (launched in 1961), and clomiphene, marketed in 1967 as Clomid to treat infertility caused by anovulation. Before long, drugs were developed which resembled oestrogen, but owing to slight modifications to its structure opposed or blocked its effects in the body, i.e were ‘oestrogen antagonists’. These were generally used to treat hormone dependent cancers, in particular breast cancer. One such drug was tamoxifen, which was synthesized in 1962 by the industrial chemist Dora Richardson, and was later shown to be oestrogenic in some tissues, but not in others, giving rise to the concept of selective oestrogen receptor modulator (referred to as SERM after the American spelling for oestrogen : ‘estrogen’).23 Tamoxifen’s ability to bind to the oestrogen receptor, which had been isolated from cells in 1968, not only made it a useful tool for investigating oestrogen metabolism, but for predicting which tumours would respond to hormone therapy, thus allowing the prevention of breast cancer in women at high risk of contracting the disease.24

From preventing, to regulating, and reversing the ‘arrow of time’

As materials, oestrogen and its analogues, whether natural or synthetic, therefore have had the capacity to interfere with time. As a component of the contraceptive pill, oestrogen prevented pregnancy, and since becoming associated with the first use of compliance packaging (the now familiar 21-day blister pack, see Figure 3), it also regulated – in this way controlling and standardizing – women’s menstrual cycle.25

Figure 3: Contraceptive pill – pill on finger + pack.26

As HRT,27 oestrogen not only revived Brown-Séquard’s dream of rejuvenation, but by halting, or even reversing the effects of time on the female body, it also helped to make it a reality. Like oestrogen, HRT has had a life trajectory. In Elizabeth Siegel Watkins’s words:

‘from its conception in the 1890s, to its infancy in the 1920s and 1930s, through its adolescent growth spurt at mid-century, to its maturity into one of the most prescribed drug in America in the 1980s and 1990s, and, in the past few years, to hints of senescence.’28

Like oestrogen therefore, HRT has had multiple identities. In the 1950s and 1960s HRT shifted from the short-term relief of menopausal symptoms to the long-term therapy for post-menopause, and ageing more generally, helping to maintain strong bones, a youthful physical appearance and stable emotional states. Then, as the baby boomer generation reached maturity, HRT was reinvented in the 1980s as a preventative health measure against bone loss and osteoporosis in active senior women, before concerns over increased risks of heart disease, stroke, blood clots and breast cancer led to its more recent fall from favour, and its return to a short-term treatment for women experiencing severe menopausal symptoms.29

Blurring boundaries and generating legacies

In time, such a panoply of drugs enabled oestrogen to be understood as far more than the simple chemical agent of femininity, and to be seen as part of the complex interplay of hormones affecting the entire metabolism, in both women and men, over the course of their entire lives. Furthermore, after it was first used as gender-affirming therapy by the Danish endocrinologist Christian Hamburger in the 1950s to treat the transgender woman Christine Sorgensen,30 and more recently since it was developed as a treatment for children suffering from gender dysphoria and/or transitioning from male to female,31 oestrogen has also helped to blur the traditional boundary between men and women, paradoxically perhaps for a material that had long been thought of as the ‘female principle’.

Yet the ubiquity of oestrogen, in drugs, and in materials more generally – both natural and manmade, more especially plastics – has generated concerns about contamination, and therefore persistence in the environment, where its legacy may be oestrogen dominance in males, as well as in females, i.e. the feminization of humankind. In its latest incarnation, ‘environmental oestrogen’ has therefore caused anxieties about the potential health impacts of the blurring of distinctions between the sexes,  leading to infertility, breast cancer, and numerous other pathologies, in men as well as women.32

In this way, and the many other ways outlined in this paper, oestrogen has not only shown itself to be a most powerful agent of change – over time, from conception to old age, and across space, from a molecular to an environmental level – it has also shown itself to act as an essential matrix, at the centre of our highly interconnected material world.


 

  1. See ‘Matter,’ Online Etymological Dictionary, https://www.etymonline.com/word/matter#etymonline_v_9723; also ‘Matter,’ Oxford English Dictionary [hereafter OED], https://www-oed-com.oxfordbrookes.idm.oclc.org/view/Entry/115083?rskey=J42dgx&result=1#eid (accessed 02.04.21). []
  2. 2. R.A. Hess et al. ‘A role for oestrogens in the male reproductive system,’ Nature 390, 6659 (4 Dec. 1997): 509-12 ; Michael Schulster et al. ‘The role of estradiol in male reproductive function,’ Asian journal of andrology 18,3 (2016): 435-40. []
  3. 3 In Biomaterials Science, biomaterials do not include materials produced by biological systems, like bone, and are normally passive rather than active. Biomaterials can be derived either from nature or synthesized in the laboratory using a variety of chemical approaches, and can be engineered to interact with biological systems for a medical purpose, either therapeutic or diagnostic. A biomaterial can also be defined as ‘An organic substance of biological origin, esp. one forming part of the structure of an organism’. ‘Biomaterial,’ OED, https://www-oed-com.oxfordbrookes.idm.oclc.org/view/Entry/273891?redirectedFrom=biomaterial#eid, (accessed 02.04.21). According to this broader definition, which is applicable to the environmental field where it refers to material of natural origin, oestrogen could therefore be classed as a ‘biomaterial’. []
  4. R. Mechoulam et al. ‘Estrogens in insects,’ Experientia 40(1984):942–944. []
  5. J.R. Rochester, ‘Bisphenol A and human health: a review of the literature,’ Reproductive Toxicolology 42(Dec. 2013):132-55 ; Evanthia Diamanti-Kandarakis et al. ‘Endocrine-disrupting chemicals: an Endocrine Society scientific statement.’ Endocrine reviews 30,4 (2009): 293-342. []
  6. Laura C. Alonso, Robert L. Rosenfield, ‘Oestrogens and puberty’, Best Practice & Research Clinical Endocrinology & Metabolism 16,1 (2002) : 13-30. []
  7.  Source: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Explanation: The central disk reads clockwise from the top, starting at day 1 of the cycle. The levels of each of the four main hormones are represented by the four coloured discs (with green representing oestrogen). The intensity of each colour denotes the concentration of the hormone in the blood. The five surrounding illustrations show the corresponding changes in the ovary and the lining of the uterus (endometrium) as it prepares for potential pregnancy. Accessible in the Wellcome Collection: https://wellcomecollection.org/works/s33u9fhg (accessed 02.04.21). []
  8. Astrid M. Horstman et al. ‘The Role of Androgens and Estrogens on Healthy Aging and Longevity,’ The Journals of Gerontology: Series A 67,11 (Nov. 2012): 1140–1152. []
  9.   J.S. Finkelstein et al. ‘Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men,’ The New England Journal of Medicine [hereafter NEJM]369,11 (12 Sept. 2013): 1011-1022. See also G. Lombardi,et al. ‘Estrogens and health in males’, Molecular and Cellular Endocrinology 178,1-2 (2001 Jun 10): 51-5. []
  10. See the ensuing discussion ‘Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men,’ NEJM (26 Dec. 2013). []
  11. Robert Frank, The Female Sex Hormone (Springfield, Baltimore: C.C. Thomas, 1929). []
  12. Nelly Oudshoorn, Beyond the Natural Body : an archaelology of sex hormones (London/New York : Routledge, 1994); Celia Roberts, Messengers of Sex : Hormones, Biomedicine and Feminism (Cambridge University Press, 2007); S. Mahfouda et al, ‘Gender-affirming hormones and surgery in transgender children and adolescents,’ Lancet Diabetes Endocrinol 7, 6 (June 2019):484-498. []
  13. Mechoulam, ‘Estrogens in insects.’ []
  14. G.W. Corner, ‘The Early History of Oestrogenic Hormones,’ Proceedings of the Society of Endocrinology 33(1965): 3-18 (3). []
  15. Corner, ‘The Early History of Oestrogenic Hormones,’ 5. []
  16. C-E. Brown-Séquard, ‘The effects produced on man by subcutaneous injection of a liquid obtained from the testicles of animals’” Lancet 137, 3438 (1889): 105–107. []
  17. Osborn Segerberg, Jr., The Immortality Factor (New York: E. P. Dutton and Co., Inc., 1974), pp. 84–85. []
  18. Oudshoorn, Beyond the Natural Body, 18. []
  19. Forrest AP. Beatson, ‘Hormones and the management of breast cancer’ J R Coll Surg Edinb. 27, 5 (Sep. 1982): 253-63 ; see also Serena Stockwell, ‘Classics in Oncology: George Thomas Beatson, M.D. (1848–1933)” CA – A Cancer Journal for Clinicians 33, 2 (March–April 1983): 105–107 []
  20. Today fully synthetic versions of these drugs, referred to as ‘conjugated oestrogens’ (CEs), exist. []
  21. Now known as diesthylstiboestrol, it was used as a form of chemical castration, thereby avoiding the risk of imprisonment at a time when sexual acts between men were a criminal offence. Andrew Hodges, Alan Turing: The Enigma (London: Vintage, 1992), Ch. 8. []
  22. Wellcome Collection:
    https://wellcomecollection.org/works/s85hw86e/images?id=cf4kgtec (date accessed 06/05/21) []
  23. V.C. Jordan, “Tamoxifen: a most unlikely pioneering medicine,” Nature Reviews Drug Discovery 2 (2003): 205-13. []
  24. Tamoxifen therefore became the first chemopreventive drug for any cancer. See V. Quirke, “Tamoxifen from failed contraceptive pill to best-selling breast cancer medicine: a case-study in pharmaceutical innovation,” Frontiers in Pharmacology (12 Sept. 2017): 1663-9812. []
  25. Demonstrating the fact that materials do not exist in isolation, but interact with each other – the blister pack was made possible by developments in materials (especially plastic) as well as packaging. P.P. Gossel, ‘Packaging the pill’, in R. Bud (ed), Manifesting Medicine (Rodopi : Amsterdam, 1999), pp. 105-22. []
  26. Source: Credit: Kate Whitley. Attribution 4.0 International (CC BY 4.0), Wellcome Collection :
    https://wellcomecollection.org/works/pep9mepb/images?id=gdxqwyse (date accessed 07/05/21). []
  27. HRT initially only included oestrogen, but later, like the pill, included both oestrogen and progestin. []
  28. Elizabeth Siegel Watkins, The Estrogen Elixir: a history of hormone replacement therapy in America (Baltimore: The Johns Hopkins University press, 2007), p. 2. []
  29. Ibid, pp. 3-4. For current advice about HRT see https://www.nhs.uk/conditions/hormone-replacement-therapy-hrt/ (date accessed 08/05/21). []
  30. C. Hamburger, Gk Sturup, E. Dahl-Iversen, ‘Transvestism; hormonal, psychiatric, and surgical treatment’, J Am Med Assoc. 152, 5 (1953) : 391-6 ; V.L. Bullough, ‘Transsexualism in history.’ Arch Sex Behav. 4,5 (Sep. 1975): 561-71. []
  31. V.L. Bullough, ‘Transsexualism in history.’ Arch Sex Behav. 4,5 (Sep. 1975): 561-71. Nowadays, in transgender youths, oestrogen is given after 12-months of puberty blockers, as oestrogen is not sufficient to halt the development of secondary male sex characteristics on its own. Vin Tangpricha, and Martin den Heijer, ‘Oestrogen and anti-androgen therapy for transgender women,’ The Lancet Diabetes & endocrinology 5,4 (2017): 291-300. []
  32. See: ‘”Environmental Estrogen: is everyone going to be a female?’ https://environmentalestrogen.wordpress.com/what-is-environmental-estrogen/ (Accessed July 31, 2020). []