What Is A GnRH Agonist?

If you’ve done a little homework on fibroid treatments or discussed treatment options with your gynecologist, you may have encountered the term “GnRH agonist”. Here’s what it is: GnRH stands for Gonadotrophin Releasing Hormone; it is a hormone that the body naturally produces and in women, it serves the function of stimulating egg production in the ovaries. The term “agonist” refers to a synthetic drug that simulates the body’s own, naturally produced material (or in this case, hormone).  Supplementing the body’s natural supply of GnRH with a GnRH agonist effectively inhibits the ovaries’ production of estrogen and testosterone, pushing the body into a menopausal state.

GnRH agonists have multiple uses in reproductive medicine, including treating pain associated with endometriosis and temporarily relieving symptoms of uterine fibroids. GnRH agonists can be used to treat heavy bleeding, one of the most common symptoms experienced by fibroid sufferers and women with endometriosis. In fact, for women taking GnRH agonists, bleeding tends to cease altogether, a condition known as amenorrhea. In this way, the treatment (also referred to as “GnRH analogue therapy”) helps to resolve anemia and a low blood cell count. When taken in advance of surgery, GnRH agonists can reduce the likelihood of a blood transfusion being required.

Furthermore, the drug’s significant effect on the growth of fibroids has been observed in many clinical studies. It’s not surprising: fibroids, benign uterine tumors, are estrogen-dependent. When estrogen levels in the body drop, fibroids shrink. By decreasing the body’s estrogen production, GnRH agonists—commercially available in such drugs as Lupron, Zoladex, Synarel, Buserelin, and Prostap—cause fibroids to shrink. Research indicates that continuous use of a GnRH agonist reduces fibroid size by approximately 50% after 3 months. Due to its fibroid-shrinking properties, GnRH agonists are commonly prescribed to women who are scheduled to undergo myomectomy; shrinking the fibroids in advance of the procedure minimizes the invasiveness of their extraction through laparoscopic surgery.

The most common symptoms experienced by patients undergoing the hormone-suppressing treatment are the symptoms typically associated with menopause: these can include hot flashes, vaginal dryness, moodiness or depression, headaches, and loss of bone density. “Add-back” hormone therapies (i.e. taking estrogen drugs) can usually provide some relief from these symptoms, without undermining the effectiveness of the primary therapy. No permanent side effects have been noted in human studies, though GnRH agonists are not indicated for long-term use. Studies have demonstrated the continuous use of a GnRH agonist, in conjunction with hormone add-back therapy to counteract bone density loss and other symptoms of estrogen deficiency, to be safe and effective for up to 2 years.

While the effects of taking a GnRH agonist may be profound, they are not permanent. Once the GnRH agonist is discontinued, estrogen levels start to return to the pretreatment state, reversing menopausal symptoms triggered by the treatment. In a study conducted by the research team of Rein et al., fibroid patients who were treated with a GnRH agonist became amenorrheic shortly after starting treatment. Four to ten weeks after discontinuing the treatment, the patients’ menses returned. The researchers also observed a rapid regrowth of fibroids once patients discontinued the GnRH agonist therapy. However, since fibroid patients GnRH agonists are most commonly prescribed in preparation for myomectomy, regrowth of fibroids following cessation of the drug is not a matter of concern.

 

SOURCES:

  1. Rein M. S. et al. “Fibroid and myometrial steroid receptors in women treated with gonadotropin-releasing hormone agonist leuprolide acetate” Fertility & Sterility. 1990; Vol. 53: pp.1018-1023
  2. American Society for Reproductive Medicine, “GnRH Agonist Therapy”, ReproductiveFacts.org: 2011. Retrieved July 10, 2015, from https://www.asrm.org/detail.aspx?id=1884
  3. Burbank, F. Fibroids, Menstruation, Childbirth, and Evolution, pp. 93-98. Wheatmark, 2009. Tucson, AZ.
  4. Friedman, A.J. et al. “Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen-progestin or progestin add-back for 2 years”, Human Reproduction. 1994; Vol. 9: pp.1618-1625

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