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

Abstract

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.

Keywords: Deep infiltrating endometriosis; nerve fibers; pain.