Early expectations and clinical trials

The first standardized preparation of male sex hormones was not put on the market by Organon until 1931, five years after the equivalent drug for women. Since 1924, Organon had been marketing an organ preparation made from testes (Testanon), but it was not standardized by biological tests. The relative delay in marketing a standardized preparation was caused mainly by technical problems in finding appropriate assay-methods for standardization and (as we have seen) in gaining access to the required amounts of raw materials.

Remarkably, the decision to develop standardized male sex hormones as an Organon product seems not to have been as self-evident as for female sex hormones. Before Organon decided to start production, Tausk had to be convinced by Laqueur of the commercial value of this product. Organon had serious doubts about the therapeutic activity of male sex hormone preparations and decided to market male sex hormone only under the condition that the clinical effects should be known in advance. Laqueur disagreed with Tausk on the necessity of clinical trials before marketing male sex hormones, and argued that “it is not the task of a pharmaceutical industry to retain the marketing of a much requested product” (Organon Archive 2 July 1930).

Technical problems further delayed the actual marketing of the first standardized male sex hormone preparation. The major problem was how to produce a highly purified hormone preparation free from other substances of similar solubility, and in particular free of female sex hormones. We saw before how, to the astonishment of many scientists, male urine and testes, applied as raw materials for the production of male sex hormones, contained not only male sex hormones but also substances defined as female sex hormones (Organon Archive 2 June 1930).

In the mean time, Laqueur initiated preliminary, small-scale clinical trials, delivering male sex hormone preparations to some of his clinician acquaintances in university clinics, both in Berlin and Amsterdam, with whom he had collaborated earlier. In January 1931, Organon started selling the first standardized male sex hormone preparation under the trade name of Hombreol (Organon Archive 3 December 1930).

What were the early expectations concerning the therapeutic value of male sex hormones? And to whom did Organon expect to sell its new product? In contrast to female sex hormones, the marketing of male sex hormones was not characterized by high expectations. On the contrary, both laboratory scientists and Organon were apprehensive. The modesty of these claims can be understood from what had happened earlier when a scientist had promoted therapy with testes preparations. Charles-Edouard Brown-Sequard had ruined his reputation by claiming rejuvenation and the revival of sexual activity in elderly male patients following the use of testes preparations (Corner 1965:iv). In the 1920s, Brown-Sequard’s claims again revived. The controversial claims about testicular therapy were not confined to the last decade of the nineteenth century but continued into the early decades of the twentieth century. Practitioners in France and the United States began to transplant monkey (and other) testes into men and animals, a practice that came to be known as “the monkey gland affair.” Similar to the early testes extracts therapy, this gland transplantation became a subject of public debate and controversy in the 1920s. This controversy was even greater and more lasting than that surrounding Brown-Sequard. The testicular transplantation practice lasted through 1930 when the surgery gradually began to lose credibility.24

To avoid a negative association of its products with these earlier speculations, Organon initially promoted male sex hormone therapy for a totally different and very specifically described indication: the treatment of hypertrophy of the prostate. Marius Tausk described this expectation in 1932 in Het Hormoon:

A disease which, by its origin, makes one think of the causal role of an insufficient hormone production, is hypertrophy of the prostate. The fact that this disease always develops later in life legitimizes in every respect the presumption that a shortage of testis hormone plays a role in this. Whether this is correct, only the clinic can prove, by trying to affect this disease with standardized preparations. More than with any other hormone, in this case the necessity arises from a close cooperation between the clinician, the experimenter, and last but not least, the technician.

(Tausk 1932a)

This restriction directed the promotion of male sex hormone therapy to urologists. The urologists were acquainted with the medical treatment of prostate hypertrophy. The major advantage of hormonal treatment of prostate hypertrophy was obvious. If male sex hormone therapy turned out to be successful, it could replace surgical intervention as the only possible treatment for this disease (Tausk 1933). This type of indication was in particular propagated by Laqueur. In 1934 Laqueur evaluated the clinical trials in cases of prostate hypertrophy in Het Hormoon as very promising, indicating that two-thirds of the cases had shown remarkable improvement (Organon Archive 27 October 1930; Tausk 1934a:25-29).

The promotion of male sex hormones as specific drugs for the treatment of prostate hypertrophy was received rather favorably. In the late 1930s Dutch urologists published only positive reports, urging general practitioners to use male sex hormones:

I would not fail to impress on you once again not to deny your prostate hypertrophy patients the chance to be relieved from their misery in a simple way.

(Capellen 1936)

In 1937 Laqueur’s colleague de Jongh concluded that the treatment of prostate hypertrophy, initiated in The Netherlands, had developed as one of the major indications for male sex hormone therapy in many other countries (Jongh 1937:49).