New prospects for luteinising hormone releasing hormone as a contraceptive and therapeutic agent.

intervene therapeutically with children exposed to disasters affecting the adults in their world. New prospects for luteinising hormone releasing hormone as a contraceptive and therapeutic agent Gonadal function is controlled by luteinising hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. Since the release of these hormones depends on secretion of hypothalamic luteinising hormone releasing hormone (LHRH), manipulation of this releasing factor has profound effects on the reproductive system. The synthesis of potent syinthetic antagonists and agonists of LHRH has provided the key, firstly, to a new approach to contraception free of the metabolic effects of steroidal contraceptives and, secondly, to the ability to induce a "medical gonadectomy." Use of the antagonists seems the most logical approach to blocking release of the gonadotrophins, but the development of sufficiently potent compounds for use in man has been arduous and clinical trials are only now getting under way.' Paradoxically, it is the agonists-originally developed to treat infertility-which have produced the most dramatic inhibitory effects. For normal function, the pituitary is stimulated by pulses of LHRH released from the hypothalamus, which in turn cause pulsatile secretion of LH, which stimulates the testis and ovary. This pattern of hormone release may be overriden by daily administration of an LHRH agonist; its prolonged biological action soon leads to a process of "down regulation" of the pituitary gonadotrophs and gonads. Administration of an agonist can disrupt the function of both the follicle and the corpus luteum in the normal cycle, but the simplest approach to contraception is to inhibit ovulation by daily treatment with an agonist, and this has been studied in trials in macaque monkeys and in women.2-8 LHRH agonists are degraded if taken orally, and nasal sprays have been developed so that the agonist may be absorbed through the nasal mucosa. In the normal cycle the gonadotrophins stimulate a follicle to develop and produce oestradiol. After the midcycle surge of LH the follicle ovulates to form a corpus luteum producing progesterone. If an agonist is taken daily, starting at the beginning of the cycle, there is an initial stimulatory phase, but continued administration of the agonist decreases the ability of the pituitary to release the large amounts of gonado-trophin necessary to cause ovulation.4 The effect on follicular development, as judged by plasma concentrations of oestradiol, varies among individuals. In about one-quarter follicular development is suppressed, while in the remainder the fluctuating oestrogen concentrations …