Remodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis

OBJECTIVE: To investigate neuronal remodeling processes in the uterine innervation, particularly a remodeling of sympathetic nerve fibers, as well as the role of estrogen in this modulation in adenomyosis. DESIGN: Retrospective case-control study. SETTING: University hospital endometriosis center. PATIENT(S): Forty-two patients with histologically proven adenomyosis and 19 patients without adenomyosis. INTERVENTION(S): Endometrial and myometrial tissue were immunohistochemically analyzed to further characterize the uterine innervation. MAIN OUTCOME MEASURE(S): Immunohistochemical analysis was used to identify PGP 9.5-, substance P-, and tyrosine hydroxylase-positive nerve fibers. The expression of the aromatase cytochrome P450 was evaluated in uterine tissue, and the expression of the estrogen receptor (ER) -α and ERβ in uterine nerve fibers was analyzed. RESULT(S): Adenomyotic lesions are not innervated. The density of sympathetic nerve fibers in the myometrium of women with adenomyosis is reduced when compared with the nonadenomyosis group. The aromatase expression in the myometrium of women with adenomyosis was increased when compared with the control group. The ERα/ERβ ratio is in trend shifted to the ERα side in the myometrial tyrosine hydroxylase-positive nerve fibers in adenomyosis compared to the controls. CONCLUSION(S): The disruption of the modulation of the uterine sympathetic innervation seems to be an important aspect in the pathogenesis of adenomyosis. Estrogen and its receptors seem to play a crucial role in the depletion of myometrial sympathetic nerve fibers.