title: Hormone replacement therapy and the risk of endometrial cancer: A systematic review.
abstract: BACKGROUND
  In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account.
  
  
  OBJECTIVE
  This systematic literature review assesses the safety of estrogen plus progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin.
  
  
  METHODS
  PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio.
  
  
  RESULTS
  28 studies were included. The observational literature found an increased risk among users of estrogen alone. Continuous combined therapy showed a lower risk than sequential combined therapy. The newer marketed micronized progesterone increased the risk notably, also when administered continuously. In most studies, tibolone was associated with an increased risk.
  
  
  CONCLUSIONS
  Use of unopposed estrogen, tibolone and sequential combined therapy increases the risk of endometrial cancer. Continuous combined therapy seems risk free, but possibly not when micronized progesterone is used.
authors.affiliation: Department of Obstetrics and Gynecology, Nordsjællands Hospital, University of Copenhagen, Denmark. Electronic address: leasjogren@live.dk.
authors.forename: Lea L
authors.initials: LL
authors.lastname: Sjögren
authors.affiliation: Department of Gynaecology, Rigshospitalet, Faculty of Health Science, University of Copenhagen, Denmark.
authors.forename: Lina S
authors.initials: LS
authors.lastname: Mørch
authors.affiliation: Department of Obstetrics and Gynecology, Nordsjællands Hospital, University of Copenhagen, Denmark.
authors.forename: Ellen
authors.initials: E
authors.lastname: Løkkegaard
mesh_terms: D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D017410:Practice Guidelines as Topic; D011372:Progestins / Q000008:administration & dosage; D012307:Risk Factors
chemical_list: D004967:Estrogens; D011372:Progestins
keywords: Endometrial cancer; Hormone therapy; Menopause; Micronized progesterone; Risk assessment; Systematic review