Early expectations and clinical trials

The marketing of female sex hormones was characterized by an atmosphere of high expectations. Ernst Laqueur described the joint venture of his laboratory and Organon as “the pursuit of the Goddess of Fortune” (E. Laqueur et al. 1927a). What kind of goddess were scientists seeking? What type of medicine did they expect to find?

In 1925, Laqueur described the hormone they so eagerly sought for as “the hormone of the female menstruation cycle” (Organon Archive 8 November 1925). This expectation is also reflected in the name that Laqueur chose for Organon’s first standardized female sex hormone preparation: Menformon, derived from the Latin words mensis (month) and formare (to make), meaning to make the menstruation.5

In the United States the medical profession raised similar expectations. Robert Frank described these in The Female Sex Hormone (published in 1929):

Since 1923 the subject of female sex hormones has attracted innumerable workers who are elbowing and jostling each other and jockeying for position in the neck and neck race to isolate and synthesize the much desired and long sought for hormone, which is bound to relieve many of the ills from which women suffer.

(Frank 1929: Introduction)

In his promotion of female sex hormones Laqueur followed the dualistic model, according to which sex hormones were conceptualized as sexually specific in origin and function, and he directed female sex hormone therapy strictly toward women. The expectation of manufacturing a medicine for the treatment of all diseases generally described as “women’s diseases” indicated a very promising market, since this therapy could be extended to all women. It is thus not surprising that Marius Tausk described the chemical isolation and identification of the female sex hormone as “finding gold in the urine of pregnant mares,” one of the sources from which scientists derived hormonal preparations (Tausk 1978: 116).

Early expectations of the therapeutic value of female sex hormones were inextricably enmeshed with cultural ideals about femininity. In Germany, female sex hormones (trade name Ovowop) were advertised with the slogan: “Women’s declining, will return with Ovowop” (Tausk 1978: 57). This dream of finding a medical therapy to induce eternal femininity is also reflected in the trade name Neogynon, suggested by Laqueur “because female sex hormones stimulate femininity and beauty” (Organon Archive 29 September 1925).

How did Organon put its first female sex hormone preparation on the market? And which market was it? Although expectations were high, the therapeutic value of female sex hormones was still largely unexplored. To whom did Organon expect to sell this new type of drug, one still not connected to any clearly defined illness? Before the actual decision was made, Laqueur tested the hormone preparation for toxicity among what he described as “five healthy persons, two women and three men,” consisting of Laqueur himself and four of his colleagues at the Pharmaco-Therapeutic Laboratory in Amsterdam, which convinced him of its safety (Organon

Archive 11 November 1925). In those days, the testing of hormone preparations by the scientists themselves as guinea-pigs was a generally accepted practice. Although Laqueur was convinced of its safety (obviously, because his colleagues did not complain of any negative effects), Ina Uyldert, a biologist who worked in Laqueur’s laboratory after 1933, later described how she had been quite ill after the administration of rather large quantities of female sex hormones.6 In January 1925, Organon decided to put its first female sex hormone preparation on the market, under the trade name Ovarnon, and began an advertising campaign (Organon Archive 1 January 1925). Organon and Laqueur discussed whether or not the campaign should be preceded by clinical trials to investigate the therapeutic activity of the drug. However, they decided that it was not necessary to wait for clinical results, and in February 1925, the first pamphlet was mailed to Dutch general practitioners (Organon Archive 7 February 1925).

The decision to start advertising before the results of clininal trials were known, and consequently having only vague ideas about the clinical activity of female sex hormones, can be understood in the context of the sharp competition among pharmaceutical companies eager to gain the leading position on the world market for this new drug, a competition mentioned already by Robert Frank.7 The decision not to perform clinical trials accelerated the process of marketing considerably. Laqueur requested a patent for Organon as the sole producer of female sex hormones in September 1925.8

The advertising campaign to Dutch general practitioners did not solve the problem that Organon was promoting a drug of which the therapeutic value was largely unknown. The only strategy for gaining information about the therapeutic utility of female sex hormones was through the organization of clinical trials. In December 1925 Laqueur wrote to Organon:

We can only learn by experience whether female sex hormone therapy will be of any clinical value…. Theoretically one cannot make the slightest prediction whether it will have any useful effects. In the end this will have to appear in practice.

(Organon Archive 12 December 1925)

At this point, Organon and Laqueur were totally dependent on the willingness and cooperation of the medical profession. Which branch of the medical profession would be helpful in solving the question of the therapeutic value of female sex hormones? Organon decided to take the question to gynecological clinics. Gynecologists were already acquainted with the study of the ovaries, and some were actively involved in the study of female sex hormones. The gynecological clinic provided an institutional context in which Organon could organize clinical trials.

The first clinical trials were organized on a small scale. In January 1926 Laqueur approached the director of the gynecological clinic in Breslau, Germany (Organon Archive 5 January 1926). Born in Obernigk (Breslau) and trained as a physician at the University of Breslau, Laqueur was more acquainted with German clinicians than with their Dutch counterparts (Anonymous 1938). At the same tune, Organon extended its advertising campaign to Germany. Laqueur also recommended Ovarnon to other gynecological clinics in Berlin (Organon Archive 8 November 1925). But the fact that the early clinical trials took place in Germany and not In The Netherlands was not only due to Laqueur’s background. In a lecture to his colleagues in the Genootschap ter Bevordering van Natuur-, Genees – en Heelkunde (Society for the Promotion of Science, Medicine and Surgery) in 1926, Laqueur complained that interest in clinical trials in The Netherlands was much smaller than abroad. In this address, Laqueur also requested the cooperation of clinicians:

Although therapeutic experiences are rather poor, it seems to us that it is now the task of the clinician to investigate the therapeutic effects of these preparations, which exert a specific biological activity in an area in which the clinician would like to exercise his influence.

(E. Laqueur et al. 1927a:2087-2,088)9

What kinds of medical indications were chosen for treatment with Ovarnon? Laqueur advised the German gynecological clinics to test Ovarnon first in female patients with menstrual disorders, in particular in cases in which menstruation was totally absent (amenorrhea).

In 1927 Laqueur extended the network to gynecological clinics in The Netherlands. One year after the initiation of clinical trials in Germany, Laqueur approached gynecologists from the Women’s Clinics of the Universities of Amsterdam and Utrecht who, obviously inspired by Laqueur’s lecture in 1926, were “very delighted and willing to cooperate in clinical trials” (Organon Archive 12 March 1927). Dutch gynecologists wondered whether female sex hormones “exerted a positive influence on the major female function: the cyclic changes in the genital apparatus with menstruation as a visible symptom” (Dongen 1929).

The organization of clinical trials in gynecological clinics was very much intertwined with the strategy of Organon to obtain the raw materials needed to manufacture hormone preparations. In this period, female urine had become the main source of raw materials for female sex hormones. Organon and Laqueur tried to gain the cooperation of Dutch gynecological clinics to deliver urine (and placentae) from their female patients. In exchange, Organon promised to distribute Ovarnon free of charge, for the purpose of arranging clinical trials. This was unusual: in earlier trials with other hormones (like insulin), the hormone preparations had been made available at manufacturing cost (Organon Archive 26 September 1927). In negotiations with clinics, Laqueur persuaded directors by emphasizing the benefits that gynecologists could reap by cooperating with Organon: “Clinics that cooperate will receive better hormone preparations for clinical trials than the preparations that are already on the market” (Organon Archive 26 September 1927).

Thus Organon gained twice from the cooperation with gynecological clinics: the network provided the institutional context for clinical trials as well as for the collection of raw materials.10 In 1927, both Laqueur and Marius Tausk paid regular visits to gynecological clinics in Germany and The Netherlands in order to discuss the clinical trials and to make arrangements for the delivery of urine and placentae (Organon Archive 26 September and 7 October 1927). The gynecologists in turn could profit from the network with the pharmaceutical industry because Organon provided them with female sex hormone preparations free of charge. Moreover, the results of clinical trials were often published in Dutch journals (Nederlands Tijdschrift voor Geneeskunde and Het Hormoon), mostly under the name of the gynecologist, thus strengthening the image of gynecology as a scientific medical profession.