title: Sequential combined transdermal and oral postmenopausal hormone replacement therapies: effects on bleeding patterns and endometrial histology.
abstract: OBJECTIVE
  To determine the endometrial response and bleeding patterns in postmenopausal women taking a sequential combined hormone replacement regimen either orally or transdermally.
  
  
  METHODS
  Seventy-two postmenopausal women with amenorrhea of 6 months or longer with follicle stimulating hormone and estradiol levels in the postmenopausal range and normal endometrium were included in the study. The patients randomly received sequential combined hormone replacement regimen with oral (n=37) or transdermal route (n=35). The total duration of treatment was 6 months (6 cycles of 28 d). The subjects kept daily bleeding diaries, and endometrial biopsies were taken at baseline and after 6 months of therapy.
  
  
  RESULTS
  The rates of adequate progestational response (secretory or atrophic) were 83.8% and 82.9% in the oral and transdermal hormone replacement groups, respectively (p>0.05). In the oral hormone replacement group, there were 16.2% of inadequate progestational response, 2.7% had endometrial hyperplasia and 13.5% proliferative endometrium. In the transdermal hormone replacement group, there were 17.1% of inadequate progestational response, 2.9% had endometrial hyperplasia and 14.3% proliferative endometrium. Cyclic bleedings occurred in 92.4% and 92% of all cycles in the oral and transdermal treatment groups, respectively. The mean duration of bleeding per cycle were 3.9+/-0.9 and 3.8+/-0.9 d in the oral and transdermal treatment groups, respectively.
  
  
  CONCLUSIONS
  Sequential combined transdermal hormone replacement therapy is as effective as oral therapy in preventing the development of endometrial hyperplasia. Satisfactory control of bleeding is achieved with both regimens.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey. sendag@med.ege.edu.tr
authors.forename: F
authors.initials: F
authors.lastname: Sendag
authors.forename: M C
authors.initials: MC
authors.lastname: Terek
authors.forename: N
authors.initials: N
authors.lastname: Karadadas
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D001706:Biopsy; D004714:Endometrial Hyperplasia / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D014592:Uterine Hemorrhage / Q000453:epidemiology