Gn-RH Agonists

Gn-RH agonists are a group of medicines that is being used for treating females afflicted with endometriosis for more than 20 years. They are customized versions of a biologically produced hormone called Gonadotropin Releasing Hormone, which is helpful in controlling the menstrual cycle.

The Gn-RH agonists are chemically similar, but are available in different kinds, like:

  • Nasal sprays
  • Daily injections
  • Monthly injections or
  • Three-monthly injections

If used in blend form with add-back medicines, the Gn-RH agonists are considered effective, safe and usually well acceptable by most of the females.

How does the Gn-RH agonists work?

Every Gn-RH agonist works precisely in the same manner. If used for more than 2 weeks constantly, they bring the production of estrogen to a halt by a series of chemical reactions in the body. The endometrial implants, thus, get deprived of the essential estrogen for their growth and render inactive and eventually degenerate.

Most of the females stop bleeding within two months of beginning the treatment. However, a few females may experience vaginal bleeding for nearly three to five days.  Some females may notice spotting for nearly 10 to 14 days after starting the treatment.

Nonetheless, you should be able to notice a marked symptomatic improvement within a period of 4 to 8 weeks after beginning your treatment. But some females may experience worsening of their symptomatic condition during the first two weeks.  Nothing to worry about, this happens only temporarily.

This happens as the body takes some time in clearing out the production of hormones.  In fact, during this phase, the levels of estrogen will increase and work in fuelling the ailment until the stabilizing effect of Gn-RH agonists begins taking place.

The returning of menstruation and ovulation is variable in females. Mostly, females menstruate within 4 to 6 weeks of their last spraying dose of nefarelin or buserelin or within 6 to 10 weeks of getting their last dose of triptorelin, leuprorelin or goserelin injection.

Presently, the standard duration of the Gn-RH agonist treatment is three to six months. Nevertheless, in Germany, the approved duration of the treatment is of 12 months with add-back medicinal therapy (5 mg Norethisterone a day). Possibly, some other countries may also follow suit.

A 3-month treatment course works as effective as a 6-month treatment course and relieves you of the painful symptoms equally.  But with 6-month treatment course, the returning of symptoms gets delayed considerably.

You may start getting the treatment after the first 2 to 4 days of  your  menstruation or periods so that the chances of taking the medicine while you are pregnant are minimized.  If you suspect that there is a possibility of your being pregnant, you are advised not to begin your treatment.

You are unlikely to get pregnant while you are using Gn-RH agonists. But you cannot just rule out the possibility.  In that eventuality, the treatment may cause miscarriage or irregularities in the developing fetus.  It is advised to use non-hormonal kinds of contraceptives, such as a diaphragm or condom or both, while you are on Gn-RH agonist treatment.

Add-back medicines

Many gynecologists advise taking add-back medicines for reducing or preventing the side effects developed with Gn-RH agonists.

Add-back therapy consists of taking one out of the following medicines simultaneously as a Gn-RH agonist:

  • A small dose of estrogen
  • A small dose of progestin, Or
  • A Tibolone alone.

The add-back therapy dose is kept small so that the usefulness of the Gn-RH agonists is not compromised.

In case your gynecologist has not prescribed any kind of add-back therapy medicine, you may put up a request before her or him.

Side effects

Menopausal-like symptoms

The side effects emanating from the Gn-RH agonists are mainly the outcome of the low levels of estrogen in your body.  And, hence they are generally restricted to the symptoms linked with the menopause.

These side effects are very common and most of the females will experience one or more. However, their severity may vary and some females may find them just intolerable.

Many females experience hot flashes or night sweats or even both of these. The other likely side effects are:

These menopausal-like indications generally begin disappearing after the treatment is stopped.

Bone thinning

The grave side effect of a Gn-RH agonist treatment is the tapering of the bones, particularly the spinal bones.

The system in which our bones are made consistently breaks down and regenerates. When the levels of estrogen drop in the body, the rate of bones breakdown increases than their regeneration rate. This results in reduced in bone density of nearly 4 to 6 per cent by the end of six-month treatment course.

The general perception is that a large amount of the bone loss during the treatment gets regenerated within six months after completing the treatment. And, within 1 to 2 years after completing the treatment, most of the lost bones, if not the entire, get regenerated.

Therefore, a single 6-month course of treatment will not usually be detrimental for women to have normal bone density. However, in females who are suspected to run the risk of developing this condition, the Gn-RH treatment may make them vulnerable to getting osteoporosis (fragile bones).

Osteoporosis is a grave condition that affects life quality severely. If it gets severe, the bones, particularly in the hips and the spine break unexpectedly.  In case of its being less severe, the vulnerability of bones to breaking increases.

Most of the females develop a certain extent of osteoporosis post-menopause. So, it is of utmost importance to keep the bone density unharmed before attaining menopause.

The most significant risk factor for osteoporosis is having a genetic history of the ailment, like your mother or grandmother suffering from it. Should you think you may also develop osteoporosis, you may like undergoing a scan of your bone density before going in for Gn-RH agonists’ treatment.

Add-back therapy benefits

Add-back therapy may help in reducing menopausal-like Gn-RH agonist treatment therapy. It helps in managing the quality of life by making the treatment tolerable.

Notably, the add-back therapy carries long-term advantages of minimizing or even preventing the bone thinning linked to the Gn-RH agonists’ treatment.


Some females experience irritation in their nose with the use of nafarelin or buserelin spray pump.  Some others may experience irritation or skin bruising around the area where injection needle is pierced using triptorelin, goserelin or leuprorelin syringes.

Usefulness for pain symptoms

Every Gn-RH agonist works in the same manner. Thus, they are uniformly helpful in degenerating endometrial implants and sinking symptoms of pelvic pain. They seem to be as effectual as progestin (synthetic progesterone) in alleviating pain.

Using Gn-RH agonists before surgery

The use of agonists is not advisable before undergoing a surgery for reducing the extent of peritoneal (superficial implants) ailment. Reducing the size or number of the implants may pose difficulties for the surgeon in identifying where precisely does the ailment exist.

The Gn-RH agonist treatment before the surgery may lessen the probability of recurring ovarian endometriomas. But its confirmation remains controversial.

Use after surgery

With 6-month course of Gn-RH agonist therapy right away after the surgery, you can reduce the risk of symptomatic recurrence or at least delay them for a considerable period of time.

The therapy is useful in managing pain associated with endometriosis rather than the pain linked to endometriosis after surgery and using oral contraceptives in the same manner. The advantages may be mainly relevant for females having an active peritoneal ailment.

Using in persistent endometriosis

If the endometriosis persistently recurs, you may go in for another Gn-RH agonist course. But the course length and the dosage between courses requires careful examination for minimizing the chances of reducing the bone density in the long-term future.

The bone density reduction in bones may be less noticeable during the second treatment course as compared to the first course.  Apart from this, add-back therapy reduces the risk of thinning of bones, and make repetitive, irregular or even constant treatment feasible for nearly 2 years.

Usefulness for infertility

The Gn-RH agonists, just like all the other hormonal treatments for curing endometriosis do not help in improving your chances of achieving pregnancy, without an assisted reproductive technique. So, you are advised not to use the agonists for infertility treatment.

Breastfeeding & Pregnancy

The use of Gn-RH agonists is not advised during your pregnancy. Since the agonists are found in breast milk, though in small quantity, their use is not advisable when you are breastfeeding your baby.

Points to Ponder

You should consult your doctor nearly 6 to 8 weeks after starting your Gn-RH treatment course for discussing the progress of the treatment. Never hesitate in contacting your doctor in case you are having issues in between your planned visits.

Moreover, Gn-RH agonists may act collectively with other medications. You are advised to inform your doctor in case you are taking any other prescribed or non-prescribed medications, including herbal medicines or complimentary therapies.

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