Gonadotropin releasing hormone (GnRH) is a small molecule synthesized in the brain which circulates to the pituitary gland where it releases the hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH in turn circulates to the ovary where it stimulates the growth of the ovarian follicle (the cyst which contains the egg which will be released at the time of ovulation) and the production of the hormone estrogen.

Gonadotropin releasing-like hormones are available as medication. Some of these drugs are called agonists. Agonists are substances which have an action similar to the hormone they resemble. Other GnRH congeners are called antagonists. Antagonists directly counteract the action of the hormone they resemble.

It is a curious property of GnRH agonists that when they are administered in a continuous fashion for more than 7-10 days, they assume an antagonistic action on the pituitary. This means that GnRH agonists will stimulate the production of FSH and LH for about one week, after which time the production of FSH and LH is suppressed. In treating endometriosis and fibroids, we utilize the suppressive effects of GnRH agonist drugs to treat diseases. For fertility treatment we may use both actions.

Fertility Treatment
GnRH agonists are frequently used in combination with fertility drugs. Both the agonist and antagonist property of these medications can be utilized when ovulation is stimulated. In the recipes referred to as "flare up", we administered GnRH agonists simultaneously with fertility drugs to amplify the stimulation of the ovary. Remember, for the first 7-10 days that these drugs are used, a woman's own FSH and LH are elevated. The woman's FSH and LH will add to the stimulation provided by the FSH and LH found in injectable gonadotropins. A flare up recipe is most often used in woman who have a sluggish response to the gonadotropins.

Another recipe involves the use of GnRH agonists or antagonists prior to the initiation of ovulation. These recipes are called "suppression" regimens. In a long suppression regimen, GnRH agonist is begun in the month prior to ovulation stimulation. Once menses has begun, we start gonadotropins. This regimen is utilized to synchronize a woman's ovaries so that no one follicle will have achieved a head start before gonadotropins are begun. For short suppression GnRH antagonist is given once gonadotropin injections have begun for the purpose of preventing premature ovulation.

In both the flare up and suppression regimens of GnRH agonists/antagonists, a woman's own LH surge is inhibited. Therefore, there is no chance that a woman will spontaneously ovulate prior to the administration of hCG. This phenomenon is useful in in vitro fertilization when we do not want a woman to have released her eggs prior to the time we go to harvest them.

Fibroids
Fibroids are benign tumors that grow from the wall of the uterus. Although most fibroids cause no symptoms, a minority of them will require treatment. Fibroids which grow into the lining of the uterus may cause disturbingly heavy menstrual periods of decrease a woman's chances of conceiving and holding a pregnancy. Large fibroids may cause abdominal pressure and discomfort.

Hormone suppression by GnRH agonists or antagonists usually shrink uterine fibroids. This reduction in the size of fibroids will continue only so long as the medication is given. Therefore, hormone suppression of fibroids is not employed as a long term solution. Rather, it is used for two or three months prior to surgery to shrink fibroid and suppress menses. Suppression of menses may allow a woman who has become anemic from loss of menstrual blood to recover to a normal blood count. Suppression of menses may allow a woman to be able to donate her own blood in case a transfusion is needed at the time of surgery.

Endometriosis
Endometriosis occurs when the type of tissue that is normally found lining the uterus is located outside of the uterus -- on the ovaries or the surfaces of the pelvis. Endometriosis can cause cramping with menses, pelvic pain at other times, pain with intercourse and/or infertility. Endometriosis is treated either with surgery or medical suppression of hormones. Occasionally, hormone suppression is used in combination with surgical treatment (laser laparoscopy, open surgery, etc.) to achieve the optimal result. Usually, GnRH agonists drugs are used for between four and six months when endometriosis is treated.

GnRH drugs cause a woman to have a very low estrogen level. With the long term use required to treat fibroids and endometriosis several side effects will result. Hot flashes will often occur when a woman's estrogen level drops. Headache and mood change are also common when the estrogen level suddenly becomes low. When used in connection with fertility drugs, the duration of estrogen deficiency is usually too short to cause side effects.

Long term deprivation of estrogen has been associated with a loss of calcium from bone which may predispose a woman to develop fractures. For this reason, we hesitate to treat a woman with more than one six month course of GnRH agonist. While we strongly recommend calcium supplementation during treatment, we recognize that calcium supplementation is in insufficient to completely prevent the loss of calcium from bone. Although not often discussed, it is likely that prolonged courses of GnRH agonists will decrease a woman's lifetime risk of breast and ovarian cancer.