Reproduction 733of progesterone). The newer contraceptive pills are very effective
and have a number of beneficial side effects, including a reduced
risk for endometrial and ovarian cancer, and a reduction in osteo-
porosis. However, there may be an increased risk for breast can-
cer, and possibly cervical cancer, with oral contraceptives.
Newer systems for delivery of contraceptive steroids are
designed so that the steroids are not taken orally, and as a result do
not have to pass through the liver before entering the general circu-
lation. (All drugs taken orally pass from the hepatic portal vein to
the liver before they are delivered to any other organ; chapter 18,
section 18.5.) This permits lower doses of hormones to be effec-
tive. Such methods include the transdermal patch, vaginal ring,
and injection of medroxyprogesterone acetate ( DMPA ). Addition-
ally, long-acting reversible contraceptives are available, including
intrauterine devices ( IUDs ) and subcutaneous implants. The long-
acting reversible devices have been judged safe and found to have
a lower failure rate than contraceptive pills.to synchronize (the dormitory effect; chapter 11, section 11.3).
Recent evidence suggests that this pheromonal effect in humans
is due to the stimulation of olfactory neurons in the nasal mucosa.
As discussed in chapter 8, the limbic system of the brain
includes regions involved in emotions. Axons extend from the
limbic system to the GnRH neurons of the hypothalamus. By
means of these neural pathways, the secretion of GnRH, and
thus of FSH and LH, can be influenced by stress and emotions.
Considering this, it is not surprising that stress can even cause
a cessation of menstruation, or amenorrhea.
Many girls who are very thin or athletic have a delayed
menarche, and women with low body fat can have irregular
cycles or amenorrhea. Functional amenorrhea is the cessation
of menstruation caused by inadequate stimulation of the ova-
ries by FSH and LH, which in turn is due to inadequate release
of GnRH from the hypothalamus. Functional amenorrhea is
most often seen in women who are thin and athletic, as well
as women under prolonged stress. Intense physical exercise
can suppress GnRH secretion, and reducing the exercise pro-
gram can reverse the amenorrhea produced by rigorous athletic
training. Leptin, secreted by adipocytes, regulates hunger and
metabolism (chapter 19); it also indirectly affects the GnRH-
secreting neurons of the hypothalamus. Because of this, a suf-
ficient amount of adipose tissue and leptin secretion is required
for ovulation and reproduction, and inadequate adiposity (and
leptin secretion) can produce a functional amenorrhea. Treat-
ment with exogenous leptin has been shown to benefit women
with functional amenorrhea by stimulating the pulsatile secre-
tion of GnRH and inducing menstrual periods.
Contraceptive Methods
Contraceptive Pills and Devices
First sold in 1960, oral contraceptives are currently used by
about 10 million women in the United States and 60 million
women worldwide. These contraceptives usually consist of a
synthetic estrogen combined with a synthetic progesterone in
the form of pills that are taken once each day for three weeks
after the last day of a menstrual period. This procedure causes
an immediate increase in blood levels of ovarian steroids
(from the pill), which is maintained for the normal duration
of a monthly cycle. As a result of negative feedback inhibition
of gonadotropin secretion, ovulation never occurs. The entire
cycle is like a false luteal phase, with high levels of progester-
one and estrogen and low levels of gonadotropins.
Because the contraceptive pills contain ovarian steroid
hormones, the endometrium proliferates and becomes secre-
tory just as it does during a normal cycle. In order to prevent an
abnormal growth of the endometrium, women stop taking the
steroid pills after three weeks (placebo pills are taken during
the fourth week). This causes estrogen and progesterone levels
to fall, permitting menstruation to occur.
The side effects of earlier versions of the birth control pill have
been reduced through a decrease in the content of estrogen and
through the use of newer generations of progestogens (analogues
Clinical Investigation CLUES
Linda was given birth control pills when she received
injections to treat her endometriosis.- What did those injections contain, and what
effect did they have on Linda’s ovarian hormone
secretion? - What do birth control pills contain, and how do they
work to prevent conception?
Rhythm Method
Studies have demonstrated that the likelihood of a pregnancy
is close to zero if coitus occurs more than six days prior to
ovulation, and that the likelihood is very low if coitus occurs
more than a day following ovulation. Conception is most likely
to result when intercourse takes place one to two days prior to
ovulation. There is no evidence for differences in the sex ratio
of babies conceived at these different times.
Cyclic changes in ovarian hormone secretion also cause
cyclic changes in basal body temperature. In the rhythm method
of birth control, a woman measures her oral basal body tempera-
ture upon waking to determine when ovulation has occurred.
On the day of the LH peak, when estradiol secretion begins to
decline, there is a slight drop in basal body temperature. Start-
ing about one day after the LH peak, the basal body temperature
sharply rises as a result of progesterone secretion and it remains
elevated throughout the luteal phase of the cycle ( fig. 20.36 ). The
day of ovulation for that month’s cycle can be accurately deter-
mined by this method, making the method useful if conception is
desired. However, the day of the cycle on which ovulation occurs
is quite variable in many women, and so the rhythm method
can be unreliable in predicting the day of ovulation for the next
month’s cycle, and thus unreliable for birth control. The contra-
ceptive pill is a statistically more effective means of birth control.