Ganong's Review of Medical Physiology, 23rd Edition

422 SECTION IV Endocrine & Reproductive Physiology
converge on the ventral hypothalamus and provoke an ovulation-inducing
release of LH from the pituitary. In species such
as rats, monkeys, and humans, ovulation is a spontaneous periodic
phenomenon, but neural mechanisms are also involved.
Ovulation can be delayed 24 h in rats by administering pentobarbital
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 antagonists
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 menstrual
cycle, but they act as effective contraceptive devices.
Intrauterine implantation of pieces of metal or plastic (intrauterine
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 prevent
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
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
IUD
> 50 mg estrogen and progestin 0.32
< 50 mg estrogen and progestin 0.27
Progestin only 1.2
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 methods.
Lancet 1982;1:841. Reproduced with permission.
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, norethindrone
has an ethinyl group on position 17 of the steroid
nucleus, so it is resistant to hepatic metabolism and consequently
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 levonorgestrel
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 intervals.
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 periods
is called secondary amenorrhea. The most common
cause of secondary amenorrhea is pregnancy, and the old clinical
maxim that “secondary amenorrhea should be considered
to be due to pregnancy until proved otherwise” has considerable
merit. Other causes of amenorrhea include emotional
stimuli and changes in the environment, hypothalamic diseases,
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 hypothalamus.
In encouraging preliminary studies, the frequency of
GnRH pulses has been increased by administration of the
orally active opioid blocker naltrexone.