title: Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.
abstract: Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events.
  
  
  
  We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model.
  
  
  
  We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81.
  
  
  
  Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.
authors.affiliation: Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First Street SW, Rochester, MN, 55905, USA. asi.noor@mayo.edu.|Division of Preventive, Occupational and Aerospace Medicine, American University of Beirut, 200 First Street SW, Rochester, MN, 55905, USA. asi.noor@mayo.edu.
authors.forename: Noor
authors.initials: N
authors.lastname: Asi
authors.affiliation: Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Khaled
authors.initials: K
authors.lastname: Mohammed
authors.affiliation: Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First Street SW, Rochester, MN, 55905, USA.|Internal Medicine Department, Georgia Regents University, Augusta, USA.
authors.forename: Qusay
authors.initials: Q
authors.lastname: Haydour
authors.affiliation: Knowledge and Evaluation Research Unit and Mayo Graduate School, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gionfriddo
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA.
authors.forename: Oscar L Morey
authors.initials: OL
authors.lastname: Vargas
authors.affiliation: Library Public Services, Mayo Clinic, Rochester, MN, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Prokop
authors.affiliation: Division of General Internal Medicine, Women's Health Clinic, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Faubion
authors.affiliation: Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D001943:Breast Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000517:prevention & control; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D064887:Observational Studies as Topic; D011374:Progesterone / Q000009:adverse effects* / Q000627:therapeutic use; D045167:Progesterone Congeners / Q000009:adverse effects* / Q000627:therapeutic use; D011372:Progestins / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D045167:Progesterone Congeners; D011372:Progestins; D011374:Progesterone
keywords: Breast cancer; Cardiovascular events; Meta-analysis; Progesterone; Synthetic progestins; Systematic review