title: Longitudinal effects of menopausal hormone treatments on platelet characteristics and cell-derived microvesicles.
abstract: Activated platelets serve as a catalyst for thrombin generation and a source of vasoactive and mitogenic factors affecting vascular remodeling. Oral menopausal hormone treatments (MHT) may carry greater thrombotic risk than transdermal products. This study compared effects of oral and transdermal MHT on platelet characteristics, platelet proteins, and platelet-derived microvesicles (MV) in recently menopausal women. Platelets and MV were prepared from blood of a subset of women (n = 117) enrolled in the Kronos Early Estrogen Prevention Study prior to and after 48 months of treatment with either oral conjugated equine estrogen (0.45 mg/day), transdermal 17β-estradiol (50 µg/day), each with intermittent progesterone (200 mg/day for 12 days a month), or placebo pills and patch. Platelet count and expression of platelet P-selectin and fibrinogen receptors were similar across groups. An aggregate measure of 4-year change in vasoactive and mitogenic factors in platelet lysate, by principle component analysis, indicated significantly lower values in both MHT groups compared to placebo. Increases in numbers of tissue factor positive and platelet-derived MV were significantly greater in the transdermal compared to placebo group. MHT was associated with significantly reduced platelet content of vasoactive and mitogenic factors representing a potential mechanism by which MHT may affect vascular remodeling. Various hormonal compositions and doses of MHT could differentially regulate nuclear transcription in bone marrow megakaryocytes and non-genomic pathways in circulating platelets thus determining numbers and characteristics of circulating MV. Thrombotic risk associated with oral MHT most likely involves liver-derived inflammatory/coagulation proteins rather than circulating platelets per se.
authors: a Department of Surgery , College of Medicine, Mayo Clinic , Rochester , MN , USA .|b Department of Physiology & Biomedical Engineering , Mayo Clinic , Rochester , MN , USA .
authors: Virginia M
authors: VM
authors: Miller
authors: c Division of Biomedical Statistics and Informatics , Mayo Clinic , Rochester , MN , USA .
authors: Brian D
authors: BD
authors: Lahr
authors: c Division of Biomedical Statistics and Informatics , Mayo Clinic , Rochester , MN , USA .|d Division of Epidemiology , Mayo Clinic , Rochester , MN , USA .
authors: Kent R
authors: KR
authors: Bailey
authors: e Division of Cardiovascular Diseases , Internal Medicine, Mayo Clinic , Rochester , MN , USA , and.
authors: John A
authors: JA
authors: Heit
authors: f Kronos Longevity Research Institute and Phoenix VA Health Care System , Phoenix , AZ , USA.
authors: S Mitchell
authors: SM
authors: Harman
authors: b Department of Physiology & Biomedical Engineering , Mayo Clinic , Rochester , MN , USA .
authors: Muthuvel
authors: M
authors: Jayachandran
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D055252:Cell-Derived Microparticles / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008137:Longitudinal Studies; D008593:Menopause / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011374:Progesterone / Q000008:administration & dosage; D012307:Risk Factors
chemical_list: D004966:Estrogens, Conjugated (USP); D011374:Progesterone; D004958:Estradiol
keywords: Estrogen; microparticles; platelet aggregation; platelet-derived factor; thrombosis