title: Relationship between testosterone, estradiol and circulating PCSK9: Cross-sectional and interventional studies in humans.
abstract: BACKGROUND
  Circulating PCSK9 levels are higher in women than men, in postmenopausal than premenopausal women, and in pregnant than non-pregnant women, suggesting that sex hormones may be related to PCSK9 levels. We have examined the relationship between serum estradiol (E2) and testosterone (T) and PCSK9, and the impact of E2 replacement therapy in women and T replacement and ablation therapy in men on circulating PCSK9.
  
  
  METHODS
  We conducted a cross-sectional study to examine the correlation between serum T (in males) and E2 (in females) and serum PCSK9. We also conducted interventional studies to examine the effect of hormonal therapy on serum PCSK9 levels.
  
  
  RESULTS
  In men, (1) serum T does not correlate with circulating PCSK9 or with LDLC in the basal state, (2) T replacement therapy does not have any effect on circulating PCSK9, and (3) T ablation therapy has mixed results. In women, (1) E2 correlates inversely with circulating PCSK9 and directly with serum LDLC, but (2) E2 replacement therapy does not have any effect on circulating PCSK9.
  
  
  CONCLUSIONS
  We demonstrate differences between men and women in the relationship of their major sex hormones with circulating PCSK9. In men, circulating PCSK9 is not related to or affected by T except for a possible effect during T ablation therapy. In women, E2 is inversely related to circulating PCSK9 but the lack of effect of E2 therapy on circulating PCSK9 suggests that the E2-related differences in PCSK9 levels may be the result of differences in receptor-mediated PCSK9 clearance through E2-induced changes rather than production of PCSK9. The studies were registered with ClinicalTrials.gov NCT00848276.
authors: Clinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address: tcooi@toh.on.ca.
authors: T C
authors: TC
authors: Ooi
authors: Clinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: A
authors: A
authors: Raymond
authors: Clinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: M
authors: M
authors: Cousins
authors: Clinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: C
authors: C
authors: Favreau
authors: Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: M
authors: M
authors: Taljaard
authors: Clinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: C
authors: C
authors: Gavin
authors: The Menopause Clinic, Shirley E. Greenberg Women's Health Centre, The Ottawa Hospital, Department of Obstetrics and Gynecology, University of Ottawa, Canada.
authors: E E
authors: EE
authors: Jolly
authors: Division of Radiation Oncology, Ottawa Hospital Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
authors: S
authors: S
authors: Malone
authors: Division of Radiation Oncology, Ottawa Hospital Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
authors: L
authors: L
authors: Eapen
authors: Chronic Disease Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Institut de Recherches Cliniques de Montréal, Université de Montréal, Montréal, Quebec, Canada.
authors: M
authors: M
authors: Chretien
authors: Chronic Disease Program, Ottawa Hospital Research Institute, The Ottawa Hospital, Ottawa, Ontario, Canada; Institut de Recherches Cliniques de Montréal, Université de Montréal, Montréal, Quebec, Canada.
authors: M
authors: M
authors: Mbikay
authors: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors: J
authors: J
authors: Mayne
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D061345:Early Medical Intervention / Q000639:trends; D004958:Estradiol / Q000097:blood*; D015914:Estrogen Replacement Therapy / Q000639:trends; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*; D012727:Sex Characteristics; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood*
chemical_list: D013739:Testosterone; D004958:Estradiol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Estradiol; Gender; LDL-cholesterol; PCSK9; Testosterone