Tolerability considerations for gonadotropin-releasing hormone analogues for endometriosis

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This review examines the safety and tolerability of gonadotropin-releasing hormone analogs for endometriosis, focusing on add-back therapies to mitigate hypoestrogenic side effects.

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Abstract

INTRODUCTION: The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may cause a not negligible rate of adverse events, in particular vasomotor symptoms and bone mineral density loss, that may limit patients' adherence and safety on long-term treatment. Several strategies have been suggested to improve the compliance to treatment. AREAS COVERED: This narrative review aims to give an overview of the safety and tolerability of GnRH-a therapy and to present the different options of steroidal and non-steroidal add-back therapies in order to reduce the hypoestrogenic side effects. EXPERT OPINION: Side effects of long term GnRH-a treatment are particularly relevant. Although it has been known the efficacy of GnRH-as for treating endometriosis-associated pain, the best schedules of therapy in terms of duration and dosages are still to be defined. The ideal treatment schedule of GnRH-a is still a matter of debate as to the optimal add-back combination.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Gonadotropin-Releasing Hormone Medication Adherence Medication Adherence Animals Animals Bone Density Bone Density Bone Density Endometriosis Endometriosis Female Female Gonadotropin-Releasing Hormone Gonadotropin-Releasing Hormone Gonadotropin-Releasing Hormone Humans Humans Steroids Steroids

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (97)

Cited by (23)

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europepmc
last seen: 2026-10-19T06:17:24.038039+00:00
openalex
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pubmed
last seen: 2026-10-08T21:27:48.458931+00:00
License: CC0 · commercial use OK