Current status of research on the control of fertility

The last decade has witnessed the introduction of methods of contraception, based for the first time on means other than mechanical blockade of spermatozoa in order to prevent their ascent to the fallopian tube. Oral contraceptives, estrogen and progestin, either in combination tablets or sequentially administered, are inhibitors of ovulation. The effect on ovulation is subsequent to suppression of pituitary gonadotropin release which, in turn, is the result of an action by the administered steroids at the hypothalamus or higher brain center. There is now considerable evidence to support the concept that the steroid feedback system, controlling the release of gonadotropins, operates at the level of the central nervous system. Harris and Michael (1964), Lisk (1962) and others have demonstrated that the implantation of crystals of estrogens or progestins in specific regions of the hypothalamus results in the cessation of gonadotropin release, and, secondarily, prevents ovulation. The specific compound used in one of the contraceptive pills, chlormadinone, has been found by Gellert and Exley (1966) to prevent post-copulatory ovulation in rabbits, under experimental conditions which suggest an action at a brain level higher than the hypothalamus. It is interesting to note that electroencephalographic changes have been reported for women on contraceptive pills (Matsumoto, 1966). Studies of this type have made it abundantly clear, that the entire axis of ovary-pituitary-central nervous system must function in concert and in balance in order to produce an ovum. These anatomical units and their humoral products then provide potential targets for controlled interference with reproduction through the ultimate effect of suppressing ovulation. Important progress has been made in the last few years in our comprehension of the manner in which the neuroendocrine link at the hypothalamus operates. Hypothalamic releasing factors, which regulate the release of follicle-stimulating hormone and luteinizing hormone have been identiXed (Schally, 1964). They appear to be dialyzable substances of relatively low molecular weight. The precise

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