Hormonal treatment of malignant diseases has been used for quite some
years now, and progress in this field is still being made at a steady
pace. The detection of new endocrine feed- back loops and the
availability of new classes of hormonal agents made hormonal
intervention with predictable outcome possible. Besides the intellectual
challenge of modulating the hormone system, an important aspect of
recent research on hormones and cancer is the reduction of
treatment-related morbidity achieved with the new hormonal strategies.
Thus, controlled intervention in the hypothalamic-gonadotropic axis is
increasingly apt to replace surgical removal of the relevant glands, i.
e., the pituitary gland or the gonads. In the same way as, for example,
aromatase inhibitors are being used as a substitute for adrenalectomy.
The concept that secretion of hypothalamic gonadotropin- releasing
hormone (GnRH), pituitary gonadotropins, and sex steroids are regulated
via negative and positive feedback loops is based on the pioneering work
of Hohlweg and Harris some 40 years ago. In 1971, a breakthrough was
achieved with the isolation, structural analysis, and synthesis of the
luteinizing hormone releasing hormone (LH-RH), or GnRH as it is now more
appropriately termed, since it provokes the secretion of both
gonadotropins, LH and FSH, and since then the progress made in this area
of research has been remarkable. Both ago- nists and antagonists of
LH-RH have been synthesized and extensively studied in preclinical and
clinical settings.