title: Histological and immunohistochemical evaluation of postmenopausal endometrium after 3 weeks of treatment with tibolone, estrogen only, or estrogen plus progestagen.
abstract: OBJECTIVE
  To evaluate histological and immunohistochemical parameters of short-term (21 days) tibolone, estrogen-only, and estrogen+progestagen treatment in the human postmenopausal endometrium.
  
  
  METHODS
  An observational, open, nonrandomized, controlled study.
  
  
  METHODS
  Three collaborating centers: Amphia Hospital in Breda, Albert Schweitzer Hospital in Dordrecht, Erasmus Medical Center in Rotterdam, the Netherlands.
  
  
  METHODS
  Thirty healthy, postmenopausal women.
  
  
  METHODS
  Control group (n = 9), no hormonal treatment; tibolone group (n = 8), patients were treated with 2.5 mg of tibolone (administered orally) every day, starting 21 days before surgery; estrogen group (n = 7), patients were treated with 2 mg of E(2) (Zumenon, administered orally; Zambon, Amerfoort; The Netherlands) every day, starting 21 days before surgery; estrogen+progestagen group (n = 6), patients were treated with 2 mg of E(2) (Zumenon, administered orally) and 5 mg of medroxyprogesterone acetate (administered orally) every day, starting 21 days before surgery.
  
  
  METHODS
  Uterine tissues were collected, and two pathologists independently assessed histology. Immunohistochemical parameters measured were estrogen receptor alpha, progesterone receptor A/B, Hoxa10, Ki67, and Bcl-2.
  
  
  RESULTS
  On the basis of a number of histological and immunohistochemical parameters measured after 21 days of treatment, it was observed that tibolone displays clearly less stimulation (proliferation) of the human postmenopausal endometrium than estrogen at the beginning of a treatment, but the stimulation is higher than with estrogen+progestagen.
  
  
  CONCLUSIONS
  Short-term (21 days) tibolone treatment results in a small stimulation of proliferation of the endometrium, and because long-term treatment with tibolone has been demonstrated to lead to an atrophic endometrium, it may be concluded that the stimulatory effect, as observed in this study, is transient in nature. It is hypothesized that tibolone first displays a more estrogenic mode of action, which over time, is counterbalanced by the induction of its progestagenic properties.
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Anet H A
authors.initials: AH
authors.lastname: Klaassens
authors.forename: F Heidy
authors.initials: FH
authors.lastname: van Wijk
authors.forename: Payman
authors.initials: P
authors.lastname: Hanifi-Moghaddam
authors.forename: Bianca
authors.initials: B
authors.lastname: Sijmons
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ewing
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Ten Kate-Booij
authors.forename: G Sjarlot
authors.initials: GS
authors.lastname: Kooi
authors.forename: Helenius J
authors.initials: HJ
authors.lastname: Kloosterboer
authors.forename: Leen J
authors.initials: LJ
authors.lastname: Blok
authors.forename: Curt W
authors.initials: CW
authors.lastname: Burger
mesh_terms: D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D008875:Middle Aged; D008938:Mitosis / Q000187:drug effects; D009652:Norpregnenes / Q000494:pharmacology*; D017698:Postmenopause / Q000378:metabolism*; D011372:Progestins / Q000494:pharmacology*; D014596:Uterine Prolapse / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: D004967:Estrogens; D009652:Norpregnenes; D011372:Progestins; C027385:tibolone