Historical perspectives in gonadotrophin therapy.

The 20th century witnessed the steady development of knowledge about the reproductive process in animals and humans. These advances led to the identification of higher centres governing the dynamics of ovarian function and to the discovery of gonadotrophic hormones. As the mechanisms of action of these hormones became increasingly understood, they began to be used in the management of infertility during the early 1930s. Hormone extracts were originally prepared from animal pituitaries and pregnant mare serum, as well as from human pituitaries, placenta and urine, with pregnancies reported following their use in the late 1930s. This review traces the constant quest to reduce risks and improve safety and efficacy of hormone preparations for patients. It describes the complex path and perils leading to the pure hormone preparations that are available today, concluding with an optimistic glimpse towards the future. Small molecules that are orally active and specific are currently being investigated, some with the capacity to bypass many parts of the receptor conformation. Here lies the immediate future of this field, utilizing low-cost, small, defined molecules to stimulate follicle growth, ovulation and corpus luteum formation. Perhaps one day the classical gonadotrophins will no longer be required in clinical treatment.