Ganong's Review of Medical Physiology, 23rd Edition

422 SECTION IVEndocrine & Reproductive Physiology

converge on the ventral hypothalamus and provoke an ovula-
tion-inducing release of LH from the pituitary. In species such
as rats, monkeys, and humans, ovulation is a spontaneous pe-
riodic phenomenon, but neural mechanisms are also involved.
Ovulation can be delayed 24 h in rats by administering pento-
barbital or various other neurally active drugs 12 h before the
expected time of follicle rupture.

Contraception

Methods commonly used to prevent conception are listed in
Table 25–8, along with their failure rates. Once conception has
occurred, abortion can be produced by progesterone antago-
nists such as mifepristone.
Implantation of foreign bodies in the uterus causes changes
in the duration of the sexual cycle in a number of mammalian
species. In humans, such foreign bodies do not alter the men-
strual cycle, but they act as effective contraceptive devices.
Intrauterine implantation of pieces of metal or plastic (intra-
uterine devices, IUDs) has been used in programs aimed at
controlling population growth. Although the mechanism of
action of IUDs is still unsettled, they seem in general to pre-
vent sperms from fertilizing ova. Those containing copper
appear to exert a spermatocidal effect. IUDs that slowly release
progesterone or synthetic progestins have the additional effect
of thickening cervical mucus so that entry of sperms into the

uterus is impeded. IUDs can cause intrauterine infections, but

these usually occur in the first month after insertion and in

women exposed to sexually transmitted diseases.

Women undergoing long-term treatment with relatively

large doses of estrogen do not ovulate, probably because they

have depressed FSH levels and multiple irregular bursts of LH

secretion rather than a single midcycle peak. Women treated

with similar doses of estrogen plus a progestational agent do

not ovulate because the secretion of both gonadotropins is

suppressed. In addition, the progestin makes the cervical

mucus thick and unfavorable to sperm migration, and it may

also interfere with implantation. For contraception, an orally

active estrogen such as ethinyl estradiol is often combined

with a synthetic progestin such as norethindrone. The pills are

administered for 21 d, then withdrawn for 5 to 7 d to permit

menstrual flow, and started again. Like ethinyl estradiol, nor-

ethindrone has an ethinyl group on position 17 of the steroid

nucleus, so it is resistant to hepatic metabolism and conse-

quently is effective by mouth. In addition to being a progestin,

it is partly metabolized to ethinyl estradiol, and for this reason

it also has estrogenic activity. Small as well as large doses of

estrogen are effective (Table 25–8).

Implants made up primarily of progestins such as levonor-

gestrel are now seeing increased use in some parts of the

world. These are inserted under the skin and can prevent

pregnancy for up to 5 y. They often produce amenorrhea, but

otherwise they appear to be effective and well tolerated.

ABNORMALITIES OF

OVARIAN FUNCTION

Menstrual Abnormalities

Some women who are infertile have anovulatory cycles; they

fail to ovulate but have menstrual periods at fairly regular in-

tervals. As noted above, anovulatory cycles are the rule for the

first 1 to 2 y after menarche and again before the menopause.

Amenorrhea is the absence of menstrual periods. If menstrual

bleeding has never occurred, the condition is called primary

amenorrhea. Some women with primary amenorrhea have

small breasts and other signs of failure to mature sexually.

Cessation of cycles in a woman with previously normal peri-

ods is called secondary amenorrhea. The most common

cause of secondary amenorrhea is pregnancy, and the old clin-

ical maxim that “secondary amenorrhea should be considered

to be due to pregnancy until proved otherwise” has consider-

able merit. Other causes of amenorrhea include emotional

stimuli and changes in the environment, hypothalamic diseas-

es, pituitary disorders, primary ovarian disorders, and various

systemic diseases. Evidence suggests that in some women with

hypothalamic amenorrhea, the frequency of GnRH pulses is

slowed as a result of excess opioid activity in the hypothala-

mus. In encouraging preliminary studies, the frequency of

GnRH pulses has been increased by administration of the

orally active opioid blocker naltrexone.

TABLE 25–8 Relative effectiveness
of frequently used contraceptive methods.

Method

Failures per

100 Woman-Years

Vasectomy 0.02

Tubal ligation and similar procedures 0.13

Oral contraceptives

> 50 mg estrogen and progestin 0.32

< 50 mg estrogen and progestin 0.27

Progestin only 1.2

IUD

Copper 7 1.5

Loop D 1.3

Diaphragm 1.9

Condom 3.6

Withdrawal 6.7

Spermicide 11.9

Rhythm 15.5

Data from Vessey M, Lawless M, Yeates D: Efficacy of different contraceptive meth-
ods. Lancet 1982;1:841. Reproduced with permission.