title: Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime.
abstract: OBJECTIVE
  Many women are seeking alternatives to conventional forms of hormone replacement. This study evaluates the endometrial effects of natural progesterone cream used in conjunction with transdermal oestradiol.
  
  
  METHODS
  Open plan study conducted over 48 weeks.
  
  
  METHODS
  Tertiary referral London teaching hospital.
  
  
  METHODS
  Women at least two years postmenopausal.
  
  
  METHODS
  Women were recruited nationally. They applied 40 mg transdermal natural progesterone cream and 1 mg transdermal oestradiol daily.
  
  
  METHODS
  Endometrial histology, assessed by pipelle endometrial biopsy, ultrasound assessment of endometrial thickness and bleeding diaries.
  
  
  RESULTS
  Fifty-four women were recruited of which 41 completed the study. Mean age was 57.4 years. Thirty-two percent of women had evidence of inadequate endometrial opposition (proliferative or hyperplastic) at the end of 48 weeks. At baseline, women had a mean endometrial thickness of 3.3 mm, which had significantly thickened to a mean of 5.3 mm by 24 weeks (P < 0.001). By 48 weeks, there was significantly greater increase in endometrial thickness from baseline in those women who displayed inadequate endometrial opposition, compared with those women who had adequate endometrial opposition (P= 0.004). At 24 weeks, 48% of women had remained entirely amenorrhoeic. By the end of the study, 35% of women had been entirely amenorrhoeic and 50% had had either no bleeding or spotting alone. The number of bleeding episodes did not reduce with time.
  
  
  CONCLUSIONS
  The dose of natural progesterone cream in this study was insufficient to fully attenuate the mitogenic effect of oestrogen on the endometrium. We would not recommend this combination of hormones to be used by postmenopausal women.
authors.affiliation: Chelsea and Westminster Hospital, London, UK.
authors.forename: Arvind
authors.initials: A
authors.lastname: Vashisht
authors.forename: Fred
authors.initials: F
authors.lastname: Wadsworth
authors.forename: Adam
authors.initials: A
authors.lastname: Carey
authors.forename: Beverley
authors.initials: B
authors.lastname: Carey
authors.forename: John
authors.initials: J
authors.lastname: Studd
mesh_terms: D000279:Administration, Cutaneous; D004338:Drug Combinations; D004717:Endometrium / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009824:Ointments; D010349:Patient Compliance; D017698:Postmenopause / Q000187:drug effects; D011374:Progesterone / Q000008:administration & dosage*; D014592:Uterine Hemorrhage / Q000209:etiology* / Q000517:prevention & control
chemical_list: D004338:Drug Combinations; D009824:Ointments; D011374:Progesterone; D004958:Estradiol