Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis.

Abstract

OBJECTIVES:

To evaluate the in vivo effect of dienogest on proliferation, apoptosis, aromatase expression, vascular density, nerve growth factor (NGF) expression and nerve fiber density in human adenomyosis tissue.

STUDY DESIGN:

Twelve women who underwent hysterectomy for adenomyosis were enrolled. Six patients received dienogest treatment prior to hysterectomy (dienogest group), and age-matched six patients who had not received any hormonal treatment for ≥3 months before surgery (control group). Cell proliferation, vascular and nerve fiber density in adenomyosis tissue were evaluated by staining for Ki67, von Willebrand factor and PGP9.5, respectively. Apoptosis was detected using the TUNEL assay. The expression aromatase and NGF were evaluated by staining for corresponding antibodies.

RESULTS:

The proportion of Ki67 positive epithelial cells was significantly lower in samples from dienogest-treated patients in comparison with controls (p<0.05). The density of blood vessels in adenomyosis was marginally lower in the dienogest group in comparison with controls but statistical significance was not reached (p=0.07). The intensity of NGF expression and the density of nerve fibers were significantly lower in the dienogest group compared with controls (p<0.05 for both).

CONCLUSION:

This study demonstrates that adenomyosis, taken from patients treated with dienogest, shows remarkable histological features, such as reductions in proliferation, NGF expression and nerve fiber density. These findings indicate the impact of dienogest on local histological events, and explains its therapeutic effect on adenomyosis.

• Authors: Arisa Takeuchi, Kaori Koga, Mariko Miyashita, Tomoko Makabe, Fusako Sue, Miyuki Harada, Tetsuya Hirata, Yasushi Hirota, Tomoyuki Fujii, Yutaka Osuga
• Journal: European journal of obstetrics, gynecology, and reproductive biology (Eur J Obstet Gynecol Reprod Biol) Vol. 207 Pg. 157-161 (Dec 2016) ISSN: 1872-7654 [Electronic] Ireland
• PMID: 27865118 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Hormonal
• NGF protein, human
• Progestins
• dienogest
• Nandrolone
• Nerve Growth Factor

Topics

• Adenomyosis (drug therapy, metabolism, pathology, surgery)
• Administration, Oral
• Adult
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects, therapeutic use)
• Apoptosis (drug effects)
• Cell Proliferation
• Combined Modality Therapy
• Down-Regulation (drug effects)
• Endometrium (drug effects, innervation, metabolism, pathology)
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Myometrium (drug effects, innervation, metabolism, pathology)
• Nandrolone (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Nerve Fibers (drug effects, metabolism, pathology)
• Nerve Growth Factor (antagonists & inhibitors, genetics, metabolism)
• Neurogenesis (drug effects)
• Progestins (administration & dosage, adverse effects, therapeutic use)