This
one is a little medical, but I think I can get everyone through it just
fine. I'll start by saying both do the same thing, they both stimulate
ovulation, but each does it in it's own way. Both are pills, both can
work great in women who are anovulatory, both work only fairly well for
regularly menstruating infertile women.
Let's
go over Clomid first. The generic name of Clomid is clomiphene
citrate. It also goes by Serophene. Clomid is a drug that has been
around since the 60’s. In the lab it was discovered that this compound
blocks estrogen. This does not sound like a good fertility drug if it’s
blocking estrogen. In fact the developers thought that since it blocks
estrogen , it may be a good contraceptive. Well it had the opposite
effect. Why? After swallowing Clomid, it gets taken through the blood
stream to all parts of the body, including the brain. The brain is
important because that is where all of the control of ovulation starts.
Normal ovulation can not happen without signals from the brain and
pituitary gland. When Clomid, the "anti-estrogen", gets to the brain,
things start happening.
More
about this in a moment, first a bit about how estrogen works. Estrogen,
like all hormones, exerts its influence by landing on a receptor. A
receptor is a protein either on the surface or inside the cell that
recognizes a hormone and binds to the hormone. It is the
receptor/hormone combination that then causes the cell to do what the
hormone says to do. For example, after estrogen binds to the estrogen
receptor the combined hormone/receptor can get the cervical cells make
mucus for example. It's very much like a lock and key. The estrogen is a
key that only works in the estrogen lock (the estrogen receptor). Other
hormones, like progesterone and testosterone, float around and then
only bind with their receptors. Like a key, different hormones have
slightly different shapes, and the receptors will only connect with a
hormone if the hormone has the right shape.
OK,
back to Clomid and the brain. When Clomid gets to the brain, because
the Clomid molecule has a similar shape as the estrogen molecule, Clomid
binds to the estrogen receptor. But because the shape of the Clomid
molecule is not exactly the same as the estrogen molecule , the estrogen
receptor Clomid combination is faulty, and can not signal the cell to
do anything. Elsewhere in the body, the cervical cells will not make
mucus. for example. The Clomid takes up all of the available places on
the receptor so that the estrogen has nowhere to land, thus the actions
of estrogen are blocked.
No
estrogen, that is what the brain thinks. The brain says, “Hey, what
happened, who turned off the estrogen?” So the brain tries to make
more. Estrogen only comes from the ovary, with a few small exceptions,
so the only way for the body to get estrogen is to stimulate the ovaries
to start ovulating. This is accomplished by the brain stimulating the
pituitary gland to put out bursts of FSH, which then travels through the
blood stream to the ovaries and gets ovulation going. For most women,
this estrogen block is not 100%. Its enough of a block to get ovulation
going, but usually the Clomid can spare complete havoc the endometrium
(uterine lining) and cervical mucus. In some women, but a small
percentage, there is complete havoc; the cervical mucus completely dries
up (overcome by insemination) and the uterine lining becomes too thin
(can not be overcome).
This
is why some doctors give estrogen and Clomid at the same time. It is
believed that the Clomid will get the ovulation started and the given
estrogen will counteract the Clomid in the uterus and cervix. I have
not had much success with this method. I have found that if the Clomid
creates havoc, adding estrogen does not help.
Clomid
works wonders for women who have irregular cycles, Clomid allow for
more frequent, predictable ovulation, and this ups the odds of
conception. Women with PCO are excellent candidates for Clomid because
they have irregular cycles, which could be anywhere from every 35 days
to every 6 months to never. Women who have irregular cycles but are
not exactly PCO also have excellent results with Clomid. Women who do
not get their periods due to exercise, eating disorders or other types
of women with “hypothalamic amenorrhea” usually do not respond to
Clomid. This is because their brains do not respond to the Clomid
because the brain knows that if there is severe stress or no food coming
in, it’s not a good time to get pregnant, so even clomid will not work.
We
ask women to take Clomid (and letrozol) early in the cycle because we
want to give the boost in FSH early so that maybe we can coax the ovary
to make more than one egg that month. FSH rises from Clomid, and it's
the FSH that really does all of the work to initiate ovulation. In
women who get periods every 4 months, it really does not matter if
Clomid is given days 5, 10 20 or 30. We would prefer if you were not
pregnant when taking Clomid (although it happens and probably not a
problem), that’s why we wither give Provera to bring on a period or do a
pregnancy test before you start. So that’s a little about Clomid. It
works by blocking estrogen from it’s receptor. More to come next time.
Thanks for reading and please read disclaimer 5/17/06.
Dr. Licciardi
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