Use of hormonal therapy is associated with reduced nerve fiber density in deep infiltrating, rectovaginal endometriosis

• Published in: Acta obstetricia et gynecologica Scandinavica Vol. 94; no. 7; pp. 693 - 700
• Main Authors: Tarjanne, Satu, Ng, Cecilia H.M., Manconi, Frank, Arola, Johanna, Mentula, Maarit, Maneck, Bharvi, Fraser, Ian S., Heikinheimo, Oskari
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2015; John Wiley & Sons, Inc
• Subjects: Adult; Contraceptives, Oral, Hormonal - therapeutic use; Deep infiltrating endometriosis; Endometriosis - metabolism; Endometriosis - pathology; Endometriosis - therapy; Endometrium - innervation; Female; Humans; Immunohistochemistry; Levonorgestrel - therapeutic use; nerve fibers; Nerve Fibers, Unmyelinated - metabolism; Nerve Fibers, Unmyelinated - pathology; Nerve Growth Factor - metabolism; pain; Progesterone Congeners - therapeutic use; Receptor Protein-Tyrosine Kinases - metabolism; Rectal Diseases - metabolism; Rectal Diseases - pathology; Rectal Diseases - therapy; Vaginal Diseases - metabolism; Vaginal Diseases - pathology; Vaginal Diseases - therapy; Young Adult; nerve fibers; Deep infiltrating endometriosis; pain
• ISSN: 0001-6349; 1600-0412
• DOI: 10.1111/aogs.12652

Objective To study the density of nerve fibers in cases of deep infiltrating endometriosis (DIE) of the rectovaginal septum in relation to various clinical factors. Design A research laboratory‐based study. Setting A tertiary center together with a research laboratory. Methods Archived DIE tissue samples from 45 women operated upon for rectovaginal septum DIE were re‐examined histologically, and by immunohistochemistry. Main outcome measures The effect of progestogens or combined oral contraceptives on the density of nerve fibers, and the expression of nerve growth factor (NGF) and its high‐affinity receptor (tyrosine kinase receptor A, Trk‐A). Results The use of hormonal therapy was associated with reduced densities of sympathetic, parasympathetic and sensory nerve fibers in DIE lesions. Density of total nerve fibers (with pan‐neuronal marker PGP9.5) was significantly lower (p < 0.05) in lesions collected from hormone‐treated women (8.6/mm², 4.2–20.8/mm²; median density, from 25th to 75th quartiles) compared with that in lesions from untreated women (24.9/mm², 11.2–34.9/mm²). DIE lesions stained strongly for NGF and its receptor Trk‐A. Expression of NGF, but not of Trk‐A, was significantly reduced during use of hormonal therapy. Conclusions Use of hormonal therapy was associated with significantly reduced nerve fiber density in DIE lesions. This may be an important mechanism of action of hormonal therapy for controlling DIE pain symptoms. The expression of estrogen‐regulated NGF and its receptor was only partially suppressed during the use of hormonal therapy, suggesting that local estrogen action is often maintained during conventional hormonal therapy in cases of DIE.