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Hormonal treatments for endometriosis: gnrh agonists HORMONAL TREATMENTS FOR ENDOMETRIOSIS: GnRH AGONISTS
GnRH agonists, also known as LHRH agonists, are a group of drugs that have been developed over the last two decades. Since the mid 1980s they have been used in clinical trials in Australia and overseas for the treatment of endometriosis. They have also been used to treat a range of other conditions including anovulation (absence of ovulation) and fibroids.
The GnRH agonists are modified versions of a naturally occurring hormone, gonadotropin releasing hormone (usually abbreviated to GnRH), which helps to control the menstrual cycle.
Initially, it was thought that the GnRH agonists would not be suitable for the treatment of endometriosis as it was assumed that they would stimulate the production of oestrogen. However, it was discovered that prolonged use of the GnRH agonists actually suppressed the production of oestrogen and caused the oestrogen levels in most women to decrease to the levels found in women following the menopause. Consequently, researchers began to investigate their use for the treatment of endometriosis.
How GnRH agonists work
The GnRH agonists eradicate endometrial implants by suppressing ovulation and oestrogen secretion. The resulting low levels of oestrogen in the body mean that the endometrial implants are no longer stimulated to grow and breakdown each month so they gradually degenerate and waste away.
Most women stop ovulating and menstruating during treatment and resume ovulation and menstruation again within one to two months of completing their treatment.
Dosages of GnRH agonists generally used
Since 1971 more than 2,000 GnRH agonists have been developed by various pharmaceutical companies. Some of them are still being developed and tested while others have been released for use in some countries. At present none of them are available in Australia for the treatment of endometriosis, except under special circumstances.
Some of the more well known GnRH agonists are Buserelin (Superfact), Naferelin (Synarel), Leuprolide (Lupron), and Goserelin (Zoladex).
None of the current GnRH agonists are effective when taken by mouth because they are broken down in the digestive system. Other methods of administering the drugs have been developed, including nasal sprays, daily injections and monthly injections.
Side effects of GnRH agonists
The side effects experienced by most women are usually a result of low oestrogen levels. The majority of women experience hot flushes and some also experience other menopausal-type symptoms, including vaginal dryness, decreased libido, headaches and depression. The side effects usually disappear soon after the cessation of treatment.
The GnRH agonists appear to have no adverse effects on the levels of fats and cholesterol in the blood.
One possible long-term side effect of GnRH agonist therapy is osteoporosis (loss of bone density). In trials conducted so far some women have shown a decrease in the density of the bones in their spines; it appears that this effect is reversed and the bone density usually returns to normal within six months of ceasing treatment.
At present it seems that this loss of bone density is not likely be a significant long-term problem if the treatment lasts only six to nine months but considerable further research is needed before the complete picture is known.
How effective are the GnRH agonists
The results of the clinical trials indicate that the GnRH agonists are effective in eradicating endometriosis and relieving its symptoms but, like all the other hormonal drugs, they have no significant effect on adhesions or endometriomas and they are not a permanent cure. Overall, the GnRH agonists appear to be as effective as Danazol. When they have been approved for use in Australia they will probably assume an important place in the hormonal treatment of endometriosis.
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