Drugs Used in Reproductive Endocrinology and Infertility
Therapeutic agents used in reproductive endocrinology and infertility are in almost all cases either naturally occurring hormones or agonists and antagonists derived from the native compounds. At present, agonists and antagonists have been developed for the hypothalamic hormone gonadotropin releasing hormone ( GnRH) and for each of the major sex steroids produced by the gonads: estrogen, progesterone, and testosterone. Several physiologic principles underlie the clinical use of the these agents. One of these is the requirement of an intact hypothalamic-pituitary-gonadal axis for normal reproductive function. Within this axis, the hypothalamic production of GnRH stimulates the synthesis and secretion of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH and FSH in turn stimulate the gonadal production of the major sex steroids. Any alteration of this axis may result in either absent or exaggerated responses within the reproductive system. Perhaps the simplest perturbation of this system occurs when a hormone is given in excess. This is done in the case of gonadotropins for ovulation induction, where exogenous LH and FSH are administered. A second method of perturbing the system is to employ the principle of the negative feedback by sex steroids on gonadotropins and GnRH. This principle can be employed either to suppress gonadal function by supplying an agonist of sex hormone, as in the oral contraceptive pill, or to augment gonadal function by administering an antagonist of the sex steroid as with clomiphene. A third method of perturbing the axis is to make use of the principle of receptor desensitization. This is extensively utilized in reproductive medicine to
By analogy to the production of excess mature oocytes, the same agents may be used to increase sperm production, albeit with a much more limited role. In this case, the use of the therapy is most effective for men who have a hormonal etiology for decreased spermatogenesis as occurs in congenital deficiency in GnRH (Kallman's syndrome) or central nervous system lesions that decrease gonadotropins. More limited efficacy is observed in cases where there is a decrease in spermatogenesis of uncertain etiology.