Organon was, however, not satisfied with the broadened and unspecific applicability of female sex hormones. As late as 1932, Laqueur complained that a well-defined clinical picture for female sex hormone therapy was still lacking (Organon Archive 13 April 1932). Organon and Laqueur therefore initiated large scale clinical trials to investigate more thoroughly the therapeutic activity of female sex hormones. In the 1930s, the organization of (for the time) large-scale clinical trials was no longer curtailed by the high prices of hormone preparations during the 1920s.
In 1932, Laqueur approached the director of the women’s clinic of an Amsterdam hospital in order to conduct a clinical trial in 100 female patients, according to the methodology of double-blind trials.15 He hoped to investigate the effects of female sex hormones in female patients with a complex of symptoms attributed to the menopause, such as high blood pressure, increased heart rate, headaches and psychological depression. The idea that menopausal symptoms could be treated with female sex hormones was not new. At the turn of the century menopausal complaints had been the major indication for treatment with ovarian preparations. But such treatment had become discredited because gynecologists were not satisfied with its results (Dongen 1929:3,781-3,782). Laqueur again suggested female sex hormone therapy for the treatment of menopausal women, expecting better results with the new preparations. To conduct these trials, Laqueur requested that Organon distribute female sex hormones free of charge. Gynecological clinics in Austria were also requested to conduct large-scale clinical trials on patients with menopausal symptoms (Organon Archive 14 September 1932).
In addition to large-scale clinical trials, Laqueur also enlisted the cooperation of a health centre in Amsterdam specializing in the treatment of rheumatism and other kinds of physical diseases, the Institute for Physical Therapy. The cooperation with this institute illustrates vividly the manner in which Organon tried to direct female sex hormone therapy as a specific treatment for women in the menopause. Specifically, in 1937, Laqueur approached the Institute for Physical Therapy to conduct clinical trials with female sex hormones in exchange for free hormone supplies from Organon.
Laqueur convinced Organon to give hormone preparations free of charge by suggesting that this institute provided an excellent place for large-scale trials which would result in scientific publications from which Organon would benefit (Organon Archive 23 February 1937).
In organizing the trials, Laqueur’s laboratory played an intermediate role between Organon and the institute. One of Laqueur’s collaborators at the Pharmaco-Therapeutic Laboratory, the biologist John Freud, was also in charge of the organization of the trials. Freud visited the institute regularly and advised the medical staff about cases in which hormone therapy would be appropriate. Subsequently, Freud reported his advice to Organon and requested the free delivery of the required hormone preparations (Organon Archive 23 February 1937).
The institutional context of this cooperative venture directed female sex hormone therapy toward the treatment of middle-aged women. These patients had previously been treated with physical therapy. The introduction of female sex hormones thus offered a new therapeutic treatment. In 1937, Laqueur summarized the clinical trials in the Institute for Physical Therapy:
If one evaluates the cases in which the health centre has asked for endocrinological advice, it is striking that until now exclusively female patients have been indicated, and that 50 per cent of these cases consisted of women in the menopause with illness of the joints and obesity.
(E. Laqueur 1937)
The hormonal treatment of these patients gradually extended from a specific therapy for obesity and rheumatism to a therapy for other diseases in elderly women. Women visiting the health centre for treatment of specific complaints were also treated for other symptoms ascribed to menopause, thus providing a wider array of medical indications for female sex hormone therapy (Organon Archive 2 November 1937).
In the 1930s, many diseases of older women were increasingly attributed to low levels of sex hormones during the menopause. Because low levels of sex hormones were defined as a “deficiency” of sex hormones, symptoms previously not defined as illness became subject to medical intervention.16 The cooperation of Organon and the Pharmaco-Therapeutic Laboratory with the Institute for Physical Therapy reflects on a small scale this broader construction of the menopause as a hormonal deficiency disease that can be treated with female sex hormones. In 1931 the German gynecologist, Bernhard Zondek, introduced a hormonal typology of menopause, suggesting a division into three periods, each characterized by a specific hormonal excretion, correlated with specific clinical symptoms: the polyhormonal phase (characterized by a large excretion of female sex hormones in the blood), the oligofolliculin phase (characterized by a decrease in female sex hormone production) and the polyprolase phase (characterized by a large quantity of gonadotropic hormone) (Hoeven 1931).
In the late 1930s, Organon promoted the treatment of menopause as one of the major indications for female sex hormone therapy. In 1938 the board of directors of Organon decided to choose menopause as the major medical indication in the yearly advertisement campaign for female sex hormone preparations. At this meeting, Organon emphasized that, in addition to these advertisements, it would be extremely important to achieve the acceptance of female sex hormone therapy as a specific treatment for menopausal symptoms by the Health Financing Institution (Organon Archive 8 December 1938). The board of directors decided to approach the management of the major Dutch industries with large numbers of female employees, for example Philips, Hero and Jamin, to inquire about the seriousness of the menopausal complaints of their female employees. In its strategy to convince the Health Financing Institution of the relevance of female sex hormone therapy for menopausal symptoms, Organon based its arguments on the economic relevance of treating the large number of women employees of menopausal age. In this manner Organon used the economic interests of others in promoting its own economic advancements. The construction of the menopause as a hormonal deficiency disease was thus also directed by economic motives (Organon Archive 19 October 1938).
In addition to the menopause, In the 1930s female sex hormone therapy also became more specifically focussed on menstrual disorders. In 1931, Marius Tausk proposed that Laqueur should initiate large-scale clinical trials to investigate the function of Menformon in menstrual disorders. Tausk suggested contacting the Dutch Council of Labor to initiate clinical trials in industrial companies with large numbers of female employees (Organon Archive 6 October 1931).17 These clinical trials served a double purpose. In addition to obtaining more systematic results on the clinical relevance of female sex hormone therapy, these trials also functioned as a major vehicle in promoting female sex hormones as the specific medical treatment for menstrual disorders.
Moreover, in the early 1930s the hormonal definition of menstruation was extended to include psychological aspects attributed to hormonal changes during the menstrual cycle. In 1931, the American gynecologist Robert Frank introduced the diagnostic category of “premenstrual tension,” a period preceding menstruation with symptoms including fatigue, a general feeling of tension, irritability and lack of ability to concentrate. Frank ascribed these symptoms to the increased activity of female sex hormones during this period of the menstrual cycle (Frank 1931: 1,053-1,057)
This reconstruction illustrates how, in the 1930s, female sex hormone therapy was promoted as a specific treatment for disorders in menstruation and menopause. The medicalization of menopause and menstruation opened up an enormous market: almost all women for many years of their lives.18
The promotion of female sex hormone therapy as a specific treatment for menstruation and menopause, however, did not change its image as a much more widely applicable treatment. In the late 1930s, female sex hormones were still being prescribed for a wide range of indications. In the Pocket Lexicon for Organ and Hormone Therapy (published in 1937) Organon recommended female sex hormone therapy in as many as 34 out of 129 indications listed in this lexicon, a rather exceptional practice compared to the applicability of other organ and hormone preparations (Anonymous 1937).