title: Continuous low-dose oestrogen and progestogen hormone replacement therapy: a randomised trial.
abstract: OBJECTIVE
  To establish the efficacy and acceptability of combined continuous low-dose oestrogen and low-dose progestogen therapy, to determine whether any of three commercially available progestogens had any advantages or disadvantages in these circumstances and whether use of the lowest clinically effective oestrogen dose affected other outcomes being measured.
  
  
  METHODS
  A 12-month, prospective, open label, single centre, randomised trial.
  
  
  METHODS
  Seventy-five postmenopausal women already receiving hormone replacement therapy in the form of conjugated equine oestrogens (CEE) (0.625 mg daily) and cyclical medroxyprogesterone acetate (10 mg) and experiencing withdrawal bleeding were changed to a continuous daily regimen of 0.3 mg CEE and a random allocation of one of three low-dose progestogens (medroxyprogesterone acetate 2.5 mg, levonorgestrel 30 micrograms or norethisterone 350 micrograms). Return to a dose of 0.625 mg CEE was permitted if required to control menopausal symptoms with separate analysis of this group when appropriate.
  
  
  METHODS
  Menopausal symptom score, clinical bleeding pattern, endometrial biopsy results, forearm bone density and content, serum lipids and side effects.
  
  
  RESULTS
  Fifteen women withdrew from the trial, five because of irregular bleeding. In the remainder, amenorrhoea was achieved in 53% by three months, in 67% by six months and in 93% by 12 months. Endometrial biopsy showed atrophic endometrium by 12 months in all but one patient, in whom minimal proliferative activity was seen. Twenty-seven women chose to return to a dose of 0.625 mg CEE. In all groups, final control of menopausal symptoms improved. All regimens were bone sparing and the lipid profile was unchanged. Minimal side effects were experienced by the patients. There was little difference in outcome between the three progestogens except that norethisterone therapy was associated with a greater prevalence of amenorrhoea at six months than was seen in the levonorgestrel and medroxyprogesterone acetate groups.
  
  
  CONCLUSIONS
  These low-dose continuous oestrogen and progestogen regimens appear an appropriate option for the postmenopausal woman wishing to eliminate withdrawal bleeding and reduce both hormonal side effects and menopausal symptoms. The long term benefits of these regimens with regard to the prevention of osteoporotic fractures, cardiovascular disease and endometrial cancer need to be further assessed over time.
authors.affiliation: Department of Obstetrics & Gynaecology, University of Adelaide, SA.
authors.forename: A H
authors.initials: AH
authors.lastname: MacLennan
authors.forename: A
authors.initials: A
authors.lastname: MacLennan
authors.forename: S
authors.initials: S
authors.lastname: Wenzel
authors.forename: H M
authors.initials: HM
authors.lastname: Chambers
authors.forename: K
authors.initials: K
authors.lastname: Eckert
mesh_terms: D015519:Bone Density; D004359:Drug Therapy, Combination; D004717:Endometrium / Q000187:drug effects; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage; D008055:Lipids / Q000097:blood; D008525:Medroxyprogesterone / Q000008:administration & dosage; D008598:Menstruation / Q000187:drug effects; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage; D011372:Progestins / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies
chemical_list: D004967:Estrogens; D008055:Lipids; D011372:Progestins; D016912:Levonorgestrel; D008525:Medroxyprogesterone; D009640:Norethindrone