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GnRH Agonists in the Treatment of Symptomatic Endometriosis: A Review

Open AccessPublished:November 20, 2022DOI:https://doi.org/10.1016/j.xfre.2022.11.009
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      Highlights

      • 1)
        Essential points: Gonadotropin releasing hormone agonists (GnRHa) are effective in treating the symptoms associated with endometriosis.
      • 2)
        Post-operative GnRHa administration decreases symptom recurrence rates after surgical treatment of endometriosis.
      • 3)
        Secondary hypoestrogenic side-effects limit the duration of use of GnRHa alone to 6 months.
      • 4)
        Hypoestrogenic side-effects can be minimized while maintaining efficacy of GnRHa and allowing extension of therapy for up to 12 months with use of an appropriate add-back.

      Abstract

      The development of highly potent gonadotropin releasing hormone agonists (GnRHa) allowed for a significant addition to options for 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 impact 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.
      The majority of 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. Hypoestrogenic side-effects including bone mineral density loss and vasomotor symptoms have limited duration of use of these agents alone to six months. The use of an appropriate add-back allows for mitigation of side-effects, while maintaining efficacy and allowing extension of use to for up to 12 months. There is a limited amount of data regarding use of GnRHa in adolescents out of concern for impact 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. The development of oral GnRH antagonists with short half-lives, variable dosing, and decreased side-effects represents an exciting alternative.

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