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Analogues of luteinising hormone-releasing hormone (LHRH) are very much in fashion. Their design is clever and they offer an effective medical alternative to surgical castra-tion in the treatment of breast and prostatic cancer. In breast cancer their use in metastatic disease is increasing steadily, and current enthusiasm is such that multicentre adjuvant therapy trials in early disease are already under way. Yet LHRH analogues are expensive (a year's supply of depot Zoladex currently costs around £1,500) and other therapeutic options are available. So how much do we really need them? The hypothalamic decapeptide LHRH stimulates pituitary gonadotrophin secretion to promote the peripheral release of ovarian oestrogens or testicular androgens. A key to its physiological function is its pulsatile release at intervals of around 90 min. Modifications at the six and ten positions in the decapeptide chain produce analogues with greater potency and a longer half-life than the parent hormone. Initially these analogues mimic LHRH with a brief surge in gonadotrophin secretion, but continuous rather than pulsatile exposure eventually down-regulates pituitary LHRH membrane receptors. This leads to a paradoxical inhibition of gonadotrophin release and a consequent marked fall in plasma oestrogens to castration levels (Harvey et al., 1985; Williams et al., 1986). In striking contrast to surgical castra-tion, the effect is entirely reversible on stopping treatment. The therapeutic possibilities for LHRH analogues in the treatment of breast cancer were quickly apparent. Experimentally they cause regression of oestrogen dependent DMBA-induced rat mammary tumours (Nicolson & May-nard, 1979). In the clinic, the analogues goserelin (Zoladex, ICI), buserelin and leuprorelin have all been shown to suppress plasma oestrogens within 2-3 weeks of starting treatment and to achieve clinical regression of metastatic breast cancer in premenopausal women (Klijn, 1984; Harvey et al., 1985; Williams et al., 1986). Initially, formulation was a problem. LHRH and its analogues are small peptides susceptible to alimentary tract digestion and therefore unsuitable for oral use. Early clinical studies therefore used daily sub-cutaneous or intra-muscular injection, and buserelin has been marketed as a nasal spray. Absorption from buccal and vaginal mucosa has also been investigated. More recently monthly depot preparations have become available for gos-erelin and leuprorelin, and this has greatly simplified administration. LHRH analogues have also been investigated in post-menopausal women. On the fact of it, this might seem as illogical as oophorectomy itself. However, buserelin has been reported as having direct inhibitory effects on a human breast cancer cell …