title: A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness.
abstract: OBJECTIVE
  To study the effect of standard and low-dose estrogen-progestin therapy (EPT), tibolone and raloxifene on the incidence of vaginal spotting/bleeding and endometrial thickness over a 5-year period.
  
  
  METHODS
  Seven hundred eighty-six postmenopausal women were studied in an open prospective design. Vaginal spotting/bleeding and endometrial thickness as assessed by transvaginal ultrasonography was compared between six categories of women over a 5-year period: three categories in women on continuous combined estrogen-progestin therapy, one category under tibolone, one category under raloxifene and one under no treatment. More specifically, women received tibolone 2.5 mg (N = 204), raloxifene HCl 60 mg (N = 137), conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg (N = 122), 17beta-estradiol 2mg/norethisterone acetate 1mg (N = 58), 17beta-estradiol 1mg/norethisterone acetate 0.5mg (N = 76) or no therapy (controls, N = 189). Women with suspected endometrial pathology were referred for hysteroscopy.
  
  
  RESULTS
  Bleeding/spotting incidence was highest among standard dose EPT users (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg: 40.1%, 17beta-estradiol 2mg/norethisterone acetate 1mg: 44.8%, p < 0.001 compared to controls). Low-dose EPT associated with lower incidence of spotting/bleeding (34.1%). The incidence under tibolone and raloxifene was 22.5% and 2.9%, respectively, while 3.2% of women not receiving therapy reported vaginal spotting/bleeding. Mean endometrial thickness was not significantly affected in any of the groups studied. The drop-out rate due to spotting/bleeding was higher in the two higher dose EPT regimens. After logistic regression analysis, age at baseline was the only significant predictor of subsequent spotting/bleeding (b = -0.25, S.E. = 0.09, p = 0.006), while menopausal age and pre-treatment serum FSH had marginal significance.
  
  
  CONCLUSIONS
  EPT, tibolone and raloxifene do not appear to associate with significant changes in endometrial thickness in the majority of cases. The low-dose EPT regimen associated with a decreased incidence of unscheduled spotting/bleeding compared to the standard dose regimens. Tibolone expressed a favorable endometrial profile, as seen in its effect on unscheduled spotting/bleeding and mean endometrial thickness. Raloxifene associated with the lowest incidence in S/B and the lowest drop-out rate.s.
authors.affiliation: 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, 27 Themistokleous Street, GR-14578 Dionysos, Athens, Greece.
authors.forename: George E
authors.initials: GE
authors.lastname: Christodoulakos
authors.forename: Dimitrios S
authors.initials: DS
authors.lastname: Botsis
authors.forename: Irene V
authors.initials: IV
authors.lastname: Lambrinoudaki
authors.forename: Vasiliki D
authors.initials: VD
authors.lastname: Papagianni
authors.forename: Constantinos P
authors.initials: CP
authors.lastname: Panoulis
authors.forename: Maria G
authors.initials: MG
authors.lastname: Creatsa
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Alexandrou
authors.forename: Areti D
authors.initials: AD
authors.lastname: Augoulea
authors.forename: Spyros G
authors.initials: SG
authors.lastname: Dendrinos
authors.forename: George C
authors.initials: GC
authors.lastname: Creatsas
mesh_terms: D000368:Aged; D004717:Endometrium / Q000187:drug effects*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008796:Metrorrhagia / Q000139:chemically induced*; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage / Q000009:adverse effects*; D010352:Patient Dropouts; D017698:Postmenopause / Q000502:physiology; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects*; D013223:Statistics as Topic
chemical_list: D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D020849:Raloxifene Hydrochloride; D005640:Follicle Stimulating Hormone; C027385:tibolone