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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What Causes Fibroids: The Known Risk Factors

 

Uterine fibroids, also known as leiomyomas, are the most common benign pelvic tumor in pre-menopausal women. According to the American Society for Reproductive Medicine, uterine fibroids will affect 8 in 10 African American women and 7 in 10 Caucasian women before menopause.

Despite the prevalence of the condition and the plethora of studies that have sought to explain it, the cause of fibroids is still not fully understood. However, evidence suggests that fibroids’ development can be attributed to a combination of genetic and hormonal traits.

Hormonal Risk Factors

The link between fibroids and hormones is well documented. Specifically, it is known that fibroids are estrogen-dependent. As a result, fibroids grow during a woman’s childbearing years, while the ovaries are naturally producing estrogen, and they typically shrink after the onset of menopause, when levels of the hormone drop. The influence of hormones on fibroid growth renders the following traits “risk factors”:

Age – The risk of fibroids increases with age, up to the point of menopause. Once menopause is reached and the body’s estrogen production naturally declines, fibroids typically shrink and – in many cases – disappear entirely.
Contraceptive use – Women who began taking oral contraceptives before the age of 16 are at a greater risk of developing fibroids. However, studies have revealed that using progestin-only injectable contraceptives is associated with a reduced risk of fibroids.

Obesity – Researchers believe that being obese increases the risk of uterine fibroid development, possibly due to the association between obesity and high circulating estrogen levels.


Genetic Risk Factors

Race – The connection between race and fibroids isn’t entirely understood, but an abundance of clinical data shows it to be a significant risk factor. Black women are nearly three times more likely to develop fibroids than white women. Furthermore, research has shown that black women tend to have larger and more symptomatic fibroids than women of other races.

Family health history – Researchers and medical practitioners have long observed a familial predisposition to fibroids. To date, various clinical studies have identified over 100 specific genes as having potential links to fibroid development. OB-GYN Dr. Donald Galen frequently observes the genetic trend in his fibroid patients: “It is common for a woman with fibroids to have a history of her mother, maternal aunt, or sister who also have fibroids, ” he says.


Other Risk Factors

Certain lifestyle and environmental traits have been thought to play a role in the development of fibroids, though clinical studies have yielded somewhat contradictory results.

Diet – Research has shown that women who eat a vegetarian diet are less likely to develop fibroids than women whose diets include meat. Some studies suggest that consuming more fruits, vegetables, and low-fat dairy products could reduce the risk of developing fibroids; however, the effectiveness of changing dietary habits in slowing the growth of existing fibroids or preventing the development of new fibroids has not been conclusively established.
While the exact cause of fibroids remains unclear, existing research points to a confluence of genetic and hormonal traits. Given the prevalence of the condition of uterine fibroids, its epidemiology will undoubtedly continue to be the subject of research. The risk factors that have been established, however, help us to understand who is susceptible to developing fibroids and what physical and lifestyle changes may prevent or minimize fibroids’ occurrence.

 

SOURCES:

  1. American Society for Reproductive Medicine, “Fibroid Tumor Video Transcript”, ReproductiveFacts.org: 2011.
  2. Retrieved July 13, 2015, from http://www.reproductivefacts.org/Fibroid_tumor_video/
  3. Stewart, E. “Uterine Fibroids”, New England Journal of Medicine. 2015; 372: 1646-55.
  4. Wise, L. et al. “Age-Specific Incidence Rates for Self-Reported Uterine Leiomyomata in the Black Women’s Health Study”, Obstetrics & Gynecology. Mar 2005; 105(3): 563–568.
  5. Levy, B., “Modern management of uterine fibroids”, Acta Obstetricia et Gynecologica. April 2008; 87: 812-823
  6. Burbank, F. Fibroids, Menstruation, Childbirth, and Evolution, pp. 89-90. Wheatmark, 2009. Tucson, AZ.