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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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Endometrial Ablation vs. Radiofrequency Ablation: What’s The Difference?

 

The term “ablation” refers to a process by which tissue is destroyed, typically using either heat (thermal ablation) or cold (cryoablation). Ablative technologies are used to treat numerous medical conditions, including gynecological issues. We often hear of two procedures in particular, endometrial ablation, and radiofrequency ablation, and many people confuse the two treatments. Don’t let the similar names deceive you though: while both procedures leverage ablative technology, they are very different in their applications. To clear up the confusion, here’s a rundown on the defining characteristics of the two ablation therapies.

Endometrial Ablation (EA)

How EA Works
Endometrial ablation is typically used to treat prolonged, abnormal uterine bleeding. It does so by ablating the lining of the uterus, known as the endometrium, permanently destroying the tissue. There are several different methods of endometrial ablation: these include freezing (cryoablation techniques), directly applying heat from fixed-frequency microwaves or radiofrequency energy; and using hot fluid through techniques like balloon endometrial ablation.

In EA, treatment is limited to the endometrial layer, the surface tissue that lines the uterine cavity, and the basalis layer, where the endometrial tissue originates. Destroying the basalis layer prevents new tissue from growing, thereby reducing or eliminating menstrual bleeding.

EA procedures are performed in an office or hospital setting, usually with the patient under conscious sedation. Patients typically go home the same day, and full recovery takes about 1-2 weeks, depending on the specific procedure.

Outcomes
Endometrial ablation is used to control prolonged, abnormal vaginal bleeding. EA is most appropriate for patients that have completed childbearing, who have not seen results from other treatment approaches, and who are seeking an alternative to hysterectomy.

In most cases, EA meets its objective: an estimated 9 out of 10 women have lighter periods or no periods after undergoing the procedure. However, it’s difficult to predict whether a woman’s bleeding will stop completely. Estimates regarding the incidence of amenorrhea (the absence of menstrual bleeding) after EA vary widely from one study to the next, but it’s typically estimated to fall between 20% and 50%. A study by El-Nashar et al. asserted that the likelihood of amenorrhea occurring after EA depends on the type of ablative technology used, as well as patient characteristics like age and uterus size. Regardless, amenorrhea is not a guaranteed outcome. “If… a woman’s goal is amenorrhea, hysterectomy is the only reliable op¬tion,” reports Dr. Joseph Sanfilippo in an update to the medical community on EA-related developments.

It is important to note that endometrial ablation is not indicated for the treatment of uterine fibroids; any destruction of fibroids in the process of ablating the endometrium is incidental. Fibroids that grow partially or entirely within the walls of the uterus (known as intramural fibroids), as well as those growing outside the uterus (subserosal fibroids), are not reached during ablation. Those that protrude into the uterine cavity (submucosal) are sometimes shaved down hysteroscopically before ablation; however, if the fibroid originates below the basalis layer of tissue, it cannot be completely eradicated during ablation and may grow back, following the procedure.

Radiofrequency Ablation (Acessa Procedure)

How RFVTA Works
Radiofrequency ablation (short for “radiofrequency volumetric thermal ablation”, or RFVTA) is a specific ablation technique that is used to treat uterine fibroids in a procedure known as Acessa. In the Acessa procedure, a controlled volume of heat is applied directly to the fibroid, killing the tissue of the fibroid while leaving healthy surrounding tissue unharmed. Once the fibroid is destroyed, the dead tissue is simply reabsorbed by the body.
In performing RFVTA, a scope and a laparoscopic ultrasound probe are inserted through the abdominal incisions. Using the scope in conjunction with the ultrasound probe allows the operating physician to precisely pinpoint the fibroids’ location. Once the fibroids have been located, the surgeon uses a special tool with a retractable electrode array (the Acessa handpiece) to ablate the fibroid with radiofrequency energy.
RFVTA is performed in an outpatient setting. The surgery is minimally invasive: with the exception of two tiny incisions (no wider than 1/4 inch) on the abdomen, there is no cutting or suturing of uterine tissue. Patients go home the same day and return to normal activities within 2-3 days.

Outcomes
Clinical research has shown radiofrequency ablation to be very effective in shrinking or completely eliminating fibroids. The use of laparoscopic ultrasound reduces the risk of symptom recurrence by allowing the physician to find and treat all fibroids present in the uterus, not just the ones that were identified through previous diagnostic imaging. At 36 months post-treatment, 90% of patients needed no additional fibroid treatment. Though objectively measured bleeding at 12 months of follow up decreased in 82% of the women treated with RFVTA, the goal of treatment was not to destroy the endometrium or induce amenorrhea but merely to treat the fibroids.
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In the field of gynecology, ablation techniques can be used in addressing multiple conditions but it’s important to understand the difference between the technologies. Radiofrequency ablation with Acessa is an effective method for treating only the uterine fibroids without harming the rest of the uterus, whereas endometrial ablation effectively controls abnormal vaginal bleeding by directly ablating the lining of the uterus. Their usefulness is entirely related to their objective, and despite the commonality of a name, these procedures are very different in the objectives they serve.

SOURCES:

  1. American Society for Reproductive Medicine, “Endometrial Ablation”, ReproductiveFacts.org: 2011. Retrieved May 28, 2015, from http://www.reproductivefacts.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/endoablation.pdf
  2. El-Nashar, S.A. et al. ” Prediction of Treatment Outcomes After Global Endometrial Ablation”, Obstetrics & Gynecology, Jan. 2009; 113(1): 97–106. doi:10.1097/AOG.0b013e31818f5a8d.
  3. Sanfilippo, J. “Update: Options in Endometrial Ablation”, Supplement to OBG Management, Dec. 2009
  4. Berman, J.M. et al. “Three Years’ Outcome from the Halt Trial: A Prospective Analysis of Radiofrequency Volumetric Thermal Ablation of Myomas”, The Journal of Minimally Invasive Gynecology, 2014.

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