title: Dienogest reduces proliferation, NGF expression and nerve fiber density in human adenomyosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan. Electronic address: kawotan-tky@umin.ac.jp.
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Makabe
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Sue
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
mesh_terms: D062788:Adenomyosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000284:Administration, Oral; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D015536:Down-Regulation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009215:Myometrium / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D009277:Nandrolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; C502240:NGF protein, human; D011372:Progestins; C023635:dienogest; D009277:Nandrolone; D020932:Nerve Growth Factor
keywords: Adenomyosis; Dienogest; Nerve fiber; Nerve growth factor; Pain