Delayed oral estradiol combined with leuprolide increases endometriosis-related pain.

B S Hurst, Bradley S. Hurst, Sheila Gardner, S C Gardner, K E Tucker, Kathleen Tucker, Caleb A. Awoniyi, C A Awoniyi, W D Schlaff, WD Schlaff
JSLS : Journal of the Society of Laparoendoscopic Surgeons · 2000 · vol. 4(2) , pp. 97–101 · PMID:10917114 · PMC3015370 · W2425280638
article OA: gold CC0 ⤵ 14 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

In a randomized trial, low-dose oral estradiol combined with leuprolide acetate for endometriosis treatment trended toward increased pain compared to leuprolide plus placebo.

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Abstract

OBJECTIVES: To determine if low-dose estrogen replacement can be added to GnRH agonist therapy after three months to reduce hypoestrogenic symptoms while allowing continued relief of pain in patients with endometriosis. MATERIALS AND METHODS: Thirteen women with endometriosis and pain were treated with six months of leuprolide acetate in a prospective, randomized double-blind placebo controlled study. After three months of therapy, six subjects initiated oral estradiol 1 mg daily, and seven received an identical placebo. RESULTS: Dysmenorrhea improved in both groups, and dyspareunia significantly improved in the GnRH agonist plus placebo group. The mean pain scores of the oral estrogen group tended to be higher than the placebo group, and hot flushes tended to be less severe with estrogen treatment. However, differences observed between the study and placebo groups did not reach statistical significance. CONCLUSION: In a prospective, randomized study, low-dose estrogen replacement increases endometriosis-related pain during GnRH agonist therapy. The study was terminated after the first 13 subjects due to the concerning trend toward recurrent symptoms in women who received oral estradiol during GnRH agonist therapy for endometriosis-related pain. With the trend toward increasing pain with estrogen add-back therapy, a larger study would not seem to be justifiable.

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Condition tags

dysmenorrheaendometriosisdyspareunia

MeSH descriptors

Dysmenorrhea Endometriosis Estradiol Fertility Agents, Female Leuprolide Administration, Oral Adult Chronic Disease Double-Blind Method Drug Therapy, Combination Dysmenorrhea Dysmenorrhea Endometriosis Endometriosis Estradiol Estradiol Female Fertility Agents, Female Fertility Agents, Female Gonadotropin-Releasing Hormone

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 (13)

Cited by (14)

Source provenance

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