Clinical Note

Gonadotropin Secretion and Antifertility Drugs

The negative feedback effects of estrogens and progesterone on gonadotropin secretion have been exploited to produce antifertility drugs. Chemical modifications that prolong their half-lives and enable them to escape destruction by the liver has made possible their administration by mouth. Preparations of estrogens alone, in combination with progestational compounds, or administered sequentially prevent follicular development by blocking gonadotropin secretion, thus preventing ovulation. Sequential administration of estrogens for 2 weeks followed by progestins and then withdrawal for a few days reproduces normal endometrial events, including menstruation. Depot injections of long-acting progestins can not only block ovulation by preventing the ovulatory surge of gonadotropin secretion but also stimulate production of dense cervical mucus, which prevents passage of sperm into the uterine cavity.

The beginning and end of cyclic ovarian activity (i.e., menarche and menopause) occur on a longer time scale. The events associated with the onset of puberty were considered in Chapter 45. Although we still do not know what biological phenomena signal readiness for reproductive development and the end of the juvenile period, it appears that the timekeeper for this process resides in the central nervous system, which initiates sexual development and function by activating the GnRH pulse generator. Termination of cyclic ovarian activity coincides with the disappearance or exhaustion of primordial follicles, but during the final decade of a woman's reproductive life there is a paradoxical doubling of the rate of loss of follicles by atresia. Aging of the GnRH pacemaker may be a factor in this acceleration of folli-cular loss, as studies in normally cycling women indicate that both the amplitude of LH pulses and the interval intervening between pulses increases with increased age.

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