Surrey, E. S. (2023). GnRH agonists in the treatment of symptomatic endometriosis: a review. F&S Reports, 4(2 Suppl), 40-45. https://doi.org/10.1016/j.xfre.2022.11.009
Surrey ES. GnRH agonists in the treatment of symptomatic endometriosis: a review. F S Rep. 2023;4(2 Suppl):40-45. doi:10.1016/j.xfre.2022.11.009
Surrey, Eric S. "GnRH agonists in the treatment of symptomatic endometriosis: a review." F&S Reports, vol. 4, no. 2 Suppl, 2023, pp. 40-45.
For EndNote, Zotero or Mendeley:
Open access
No open license is recorded for this paper. Reuse terms are set by the publisher.
Open Access
Free full text on PubMed Central (PMC10201290)
Author affiliations
1 institution
Colorado Center for Reproductive Medicine03v2wv079
Linked to ROR, the Research Organization Registry
RRM Academy Synopsis
GnRH agonists reduce endometriosis symptoms during six-month treatment
A 2023 narrative review of trials in women with symptomatic endometriosis reports that GnRH agonists, which lower estrogen, reduced endometriosis symptoms in randomized trials. Side effects limited use of the drugs alone to six months. Add-back hormone therapy can reduce those side effects and allow treatment for up to 12 months.
Key Findings
In a 6-month double-blind trial of 213 women, disease reduction occurred in more than 80% of women, with no differences among the nafarelin and danazol groups.
Two randomized trials of 622 women found similar symptom improvement with goserelin and danazol. Bone mineral density decreased by 5.4% with goserelin and increased by 1.0% with danazol.
After cytoreductive laparoscopic surgery, six months of nafarelin significantly decreased recurrence compared with placebo in a multicenter trial of 109 women.
A retrospective series of 130 women treated with various GnRH agonists reported a 53.4% recurrence rate five years after therapy: 74.4% with severe disease and 36.9% with minimal disease.
Symptom relief was similar across all four groups in a 12-month placebo-controlled add-back trial. Among 1,285 women on depot leuprolide acetate in a claims analysis, 32% used any type of add-back.
Interpretation
The article is a narrative review of studies its author considers salient, mainly randomized trials. The author describes the evidence as varied, with inconsistent outcome measures, no standard symptom scales in early trials, and little long-term follow-up. Most trials checked symptoms 12 to 24 weeks after therapy. The five-year figure comes from a retrospective series. Virtually all trials enrolled women 18 or older, and fertility falls outside the review's scope. The author judges recurrence rates to appear no greater than after surgery or other medical therapies and advises against first-line use.
RRM Context
GnRH agonists suppress estrogen while a woman takes them. They belong to the suppressive medications that RRM sets aside to find and treat the cause of endometriosis. In this review, symptoms appear to return after therapy in studies that tracked recurrence. Excision removes the disease itself and is the surgical standard in restorative practice.
Our editorial summary of this paper, not the article's abstract.
Abstract
The development of highly potent gonadotropin-releasing hormone agonists (GnRHa) allowed for a significant addition to options for the medical management of symptomatic endometriosis. Pituitary GnRH receptor down-regulation leads to a hypogonadotropic and secondary hypoestrogenic state resulting in lesion regression and symptom improvement. There may be an additional effect of these agents on the inflammatory processes associated with endometriosis as well. This is a review of critical milestones in the clinical application of these agents. Most initial trials of various GnRHa employed danazol as a control and demonstrated general equivalence in reducing symptoms and extent of lesions but without hyperandrogenic side effects and adverse metabolic changes induced by the latter. Short-acting GnRHa is administered intranasally or subcutaneously. Longer-acting preparations are administered intramuscularly or as subcutaneous implants. GnRHa also decrease symptom recurrence rates after surgical management. The hypoestrogenic side effects, including bone mineral density loss and vasomotor symptoms, have limited the duration of use of these agents alone to six months. The use of an appropriate add-back allows for the mitigation of side effects while maintaining efficacy and allowing extension of use for up to 12 months. There is a limited amount of data regarding the use of GnRHa in adolescents out of concern for the effect on developing bone. These agents should be used with caution in this group. The lack of dose flexibility, need for parental administration, and side effect profiles represent drawbacks to GnRHa use. The development of oral GnRH antagonists with short half-lives, variable dosing, and decreased side effects represents an exciting alternative.
03v2wv079 