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A Brief Lesson about Hormones
A "normal' menstrual cycle is 28 days
and there are two important organs in the female's body
that control ovulation. The hypothalamus, located at the
base of the brain, signals the pituitary gland to produce
2 gonadotropin hormones that are essential for ovulation.
The first hormone is FSH (follicle stimulating hormone),
which acts upon the ovary to cause growth of a dominant
follicle (each follicle contains one egg) each month.
On about day 12-14 of the menstrual cycle,
the second hormone, LH (luteinizing hormone) surges and
causes ovulation (release of the egg). The egg is then swept
up into the tube where it will meet sperm to fertilize.
Two other hormones are also essential to ovulation and maintaining
pregnancy. Estrogen helps to build a good endometrium (uterine
lining) and rises when the egg matures. Progesterone works
in the second half of the cycle to maintain and thicken
the endometrium to support a pregnancy.
The hypothalamus can be thought of as "the
hormone thermostat" because it monitors the levels
of LH, FSH, estradiol and other hormones. For example, as
estrogen levels increase, the hypothalamus signals the pituitary
to decrease FSH production. These adjustments are mediated
by gonadotropin releasing hormone GnRH that is released
by the hypothalamus. Higher levels of GnRH stimulate the
pituitary to release more FSH.
Clomiphene Citrate (Serophene, Clomid),
Letrozole
 Clomiphene
Citrate is a commonly used medication for ovulation
induction. Clomid induces ovulation by acting at the
level of the hypothalamus to compete with estrogen binding
sites while FSH directly stimulates the ovaries. Clomid
is usually the "first choice" drug used by women
attempting pregnancy who are not ovulating regularly.
Letrozole is a new ovulation induction drug
(aromatase inhibitor) similar to Clomid except that it is
much less likely to thicken the cervical mucus or block receptors on the lining of the uterus.
The hormone "pathways" discussed
above must be in working order for Clomiphene or Letrozole
to induce ovulation. Maternal diseases and hormonal irregularities
can have a major impact on the pathways to the organs that
regulate ovulation.
Clomiphene is not always the best medication for women who
do not ovulate and a complete history, physical examination,
blood tests and X-rays are necessary prior to initiating
therapy.
Clomiphene is usually taken on days 5-9 or
3-7 of the menstrual cycle. Doses usually start at 50 mg
per day and may be increased in subsequent cycles if ovulation
does not occur. Clomiphene causes the pituitary to increase
its release of FSH and LH, thus causing the ovary to select
and grow a dominant follicle(s) and then ovulate. Once regular
ovulation is occurring there is no advantage to increasing
Clomid's dosage.
Lab
tests, ovulation predictor kits (OPK), and ultrasound
help us monitor Clomid cycles. Blood tests are also used
to monitor hormones such as estrogen and progesterone. The
OPK test looks for a surge of LH, which occurs 24-36 hours before
ovulation. Ultrasound allows us to see the development of
the follicles and subsequent ovulation.
Clomiphene is a comparatively inexpensive and
safe drug that is very useful for ovulation induction. However,
there are a few facts, which must be considered in order
to fully appreciate Clomid.
First, the cumulative (total) pregnancy rate
with clomiphene is approximately 40% and is highly dependent
upon the cause(s) of infertility. Second, approximately
85% of patients will ovulate on clomiphene. Third, most
pregnancies, which occur on clomiphene, do so within the
first 3 cycles of therapy. Fourth, very few pregnancies
occur with clomiphene after 6 cycles of usage. And finally,
one must realize that other factors, such as endometriosis,
male factor, etc. have an influence on pregnancy rates.
There are Clomid studies that suggest there
is an increased incidence of ovarian cancer following its
usage. However, these studies have many inconsistencies,
which bring their validity into question. Also, they show
that the risk does not occur unless there has been more
than one year of Clomid use. More recent and controlled
studies with large numbers of patients show no increased
risk of ovarian cancer. This is at least in part explained
by the fact that the infertile patient is at increased risk
of ovarian cancer, but that pregnancy offers some degree
of protection.
Clomid side effects may include hot flashes,
headaches, blurred vision, nausea, breast tenderness, mood
changes and bloating. There is a small risk of hyperstimulation
(growing too many follicles), which may require a cycle
of rest to let the ovaries return to normal size before
stimulating again. The multiple birth rates on Clomid are
approximately 8-10% of pregnancies are usually twins.
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