title: Ultra-low-dose estradiol and norethisterone acetate: bleeding patterns and other outcomes over 52 weeks of therapy.
abstract: BACKGROUND
  Continuous combined hormone replacement therapy (HRT) with 0.5 mg 17β-estradiol (E2) + 0.1 mg norethisterone acetate (NETA) received marketing approval based on 24-week results. The current study collected data up to 52 weeks, including consideration of bleeding, a major reason for stopping HRT.
  
  
  METHODS
  This 52-week (13 lunar-month), non-interventional, prospective study involved 169 women from Norway and Sweden receiving daily oral 0.5 mg E2 + 0.1 mg NETA to treat menopausal symptoms. Incidences and cumulative rates of amenorrhea (no bleeding or spotting) and no bleeding (women could have spotting) were evaluated, together with hot flushes and quality of life.
  
  
  RESULTS
  Overall, > 78% and > 90% of subjects were amenorrheic or had no bleeding, respectively, in each of the first 3 lunar months, while > 88% and > 96% were amenorrheic or had no bleeding, respectively, in each of lunar months 10, 11 and 12. Cumulative rates of amenorrhea and no bleeding were 67% and 83%, respectively, in lunar months 1-3, and 84% and 94%, respectively, in lunar months 10-12. The number of hot flushes declined during treatment (means at weeks 1, 12 and 52, respectively: 15.5, 5.0 and 4.1 [mild]; 19.0, 3.0 and 2.3 [moderate]; 10.8, 1.1 and 0.9 [severe]). Improvement in all four domains of the Menopause-Specific Quality of Life-Intervention questionnaire (vasomotor, psychosocial, physical and sexual) was evident by week 26.
  
  
  CONCLUSIONS
  For women receiving 0.5 mg E2 + 0.1 mg NETA, lack of bleeding-related side-effects, together with beneficial effects on hot flush symptoms and quality of life, may promote treatment continuance.
authors.affiliation: * University of Göteborg , Göteborg , Sweden.
authors.forename: L-Å
authors.initials: LÅ
authors.lastname: Mattsson
authors.forename: H E
authors.initials: HE
authors.lastname: Ipsen
authors.forename: C-J
authors.initials: CJ
authors.lastname: Granqvist
authors.forename: M
authors.initials: M
authors.lastname: Kokot-Kierepa
mesh_terms: D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage*; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D009664:Norway; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013548:Sweden; D016896:Treatment Outcome; D014592:Uterine Hemorrhage / Q000188:drug therapy*
chemical_list: D003280:Contraceptives, Oral, Synthetic; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone
keywords: BLEEDING; CONTINUOUS COMBINED HORMONE REPLACEMENT THERAPY; ESTRADIOL; HOT FLUSHES; MENOPAUSE; NORETHISTERONE ACETATE; QUALITY OF LIFE; ULTRA-LOW-DOSE