Safety of current strategies to manage moderate to severe pain in patients with endometriosis

Simone Ferrero, Fabio Barra, Giulia Vatteroni, Francesco Paolo Rosato, Francesco Rosato, Giulio Evangelisti, Michele Paudice, Valerio Gaetano Vellone
Expert opinion on drug safety · 2025 · vol. 25(2) , pp. 245–258 · doi:10.1080/14740338.2025.2547017 · PMID:40788342 · W4413101888
review OA: closed CC0 ⤵ 1 in-corpus citation
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review evaluates the safety of hormonal therapies for endometriosis pain, finding combined contraceptives and progestins effective but noting side effects, while GnRH agonists and antagonists offer alternatives with distinct safety concerns like hypoestrogenism and bone density loss.

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Abstract

INTRODUCTION: Medical therapy is crucial in the long-term management of endometriosis, and its clinical efficacy must be balanced with a favorable safety profile. AREAS COVERED: This review aims to provide a comprehensive overview of available drugs for the treatment of endometriosis, with an emphasis on their safety. A literature search was conducted using MEDLINE. EMBASE. and the Cochrane Library. Reference lists of relevant articles and recent book chapters were also examined. EXPERT OPINION: First-line therapies include combined contraceptives and progestins, both effective in reducing pain. Combined contraceptives commonly cause breakthrough bleeding, nausea, headaches, breast tenderness, and libido changes. Progestins may lead to depression, decreased libido, weight gain, breast tenderness, and lipid alterations. Gonadotropin-releasing hormone agonists are second-line options but are limited by hypoestrogenic side effects, including vasomotor symptoms, urogenital atrophy, and bone mineral density (BMD) loss. Add-back therapy with norethindrone acetate or low-dose combined contraceptives mitigates these effects. GnRH antagonists provide immediate suppression without flare-up and may improve adherence; however, hot flushes and BMD loss remain concerns. While all hormonal therapies are suppressive rather than curative, optimizing safety and tolerability is essential for sustained use and symptom control.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Pain Pain Pain Pain Pain Pain Pain Pain Pain Contraceptives, Oral, Combined Contraceptives, Oral, Combined

Citation neighborhood

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. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (100)

Cited by (1)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-29T00:31:05.001745+00:00
License: CC0 · commercial use OK