title: A low-dose start in hormone replacement therapy provides a beneficial bleeding profile and few side-effects: randomized comparison with a conventional-dose regimen.
abstract: OBJECTIVE
  To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT.
  
  
  METHODS
  An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control.
  
  
  RESULTS
  The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported.
  
  
  CONCLUSIONS
  Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control.
authors.affiliation: Sahlgrenska University Hospital, Department of Obstetrics and Gynecology, Gothenburg, Sweden.
authors.forename: L A
authors.initials: LA
authors.lastname: Mattsson
authors.forename: S O
authors.initials: SO
authors.lastname: Skouby
authors.forename: J
authors.initials: J
authors.lastname: Heikkinen
authors.forename: R
authors.initials: R
authors.lastname: Vaheri
authors.forename: J
authors.initials: J
authors.lastname: Mäenpää
authors.forename: U
authors.initials: U
authors.lastname: Timonen
mesh_terms: D000368:Aged; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D014592:Uterine Hemorrhage / Q000517:prevention & control*
chemical_list: D003271:Contraceptive Agents, Female; D004338:Drug Combinations; D004958:Estradiol; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone