day of cycle figure 13-18 Serum steroid relationships during the 4-day hamster estrous cycle. The dashed vertical line indicates the time of the critical period for the ovulatory surge of the gonadotropins. Abbreviations: c, cytosol; E^ 17/3-estradiol; n, nuclear; P, progesterone; Re, estrogen receptor; Rp, progesterone receptor. Modified with permission from Leavitt, W.W. (1983). Hormonal regulation of estrogens and progesterone receptor system. In "Biochemical Actions of Hormones" (G. Litwack, ed.), Vol. 10, p. 329. Academic Press, New York.

tiveness of various contraceptive methods. Of the various methods available for contraception, only the use of oral steroids and the "rhythm" method are strictly based on endocrinological principles.

The rhythm method of contraception is predicated on the following facts: (1) the human ovum can be fertilized for only about 24 hr after ovulation; (2) spermatozoa are competent to fertilize an ovum only up to 48 hr after coitus; and (3) ovulation usually occurs 12-16 days before the onset of menstruation. Therefore, if a woman has accurately established the length of her menstrual cycles, she can calculate her personal fertile period by subtracting 18 days from her previous shortest cycle and 11 days from her previous longest cycle. Then, in each subsequent cycle, the couple should abstain from coitus during this calculated fertile interval. The failure rate in one study assessing the effectiveness of the rhythm method was reported to be 15 pregnancies per 100 woman years. The principal reason for failure is the irregularity of the menstrual cycle even in women with previously regular cycles. Since progesterone causes an increase in basal body temperature, the effectiveness of the rhythm method can be increased by abstinence for 48 hr after the rise in body temperature. Under these circumstances, the failure rate was only 6.6 pregnancies per 100 woman years (Marshall, 1968).

The steroid contraceptive pill is the most widely used method of contraception; worldwide some 50 million women take some form of oral contraceptive. Figure 13-21 presents the structure of some of the presently employed synthetic oral contraceptives. There are two types of oral contraceptives: (a) a formulation containing combinations of estrogen with a progestin (the "combined" pill) and (b) a formulation with only a progestin.

In the combined pill, the most frequently used form of estrogen is ethinylestradiol or mestranol, while the progestin is present as either norethindrone, levonorgestrel, ethynodiol, or medroxyprogesterone. The combined pill is normally given continuously for 3 weeks, followed by a "blank" pill for the fourth week to permit the process of menstruation to occur and to establish the regularity of taking the daily pill. The combination pill prevents the development of the ovarian follicle via the estrogen inhibiting the release of FSH and interfering with GnRH release. In addition, the progestin inhibits the release of LH, so as to prevent ovulation.

In the progestin-only pill, the drugs employed are either ethynodiol, levonorgestrel, megestrol, norges-trol, or norethindrone. The pill is taken continuously. The progestin-only pill primarily acts upon the cervical mucus to make the environment inhospitable to sperm and also to block implantation.

The antiprogestin, mifepristone (RU-486), is used in some countries to provide a medical alternative to surgical termination of pregnancy (see Figure 13-21). When mifepristone is administered orally within 50 days of the last menstrual period, followed 48 hr later by a prostaglandin (given as an intravaginal pessary), a complete abortion results in 95% of the cases.

B. Anovulation

The inability of a woman to become pregnant may, in some instances, be due to a lack of ovulation. There are four chief ways to induce ovulation; these include the administration of clomiphene (a nonsteroidal compound with weak estrogen activity), gonadotropins (LH and or FSH), or bromoergocriptine (see Figure 14-23) or the surgical procedure of ovarian

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