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Nathan Goodyear

Hospitalization for pulmonary embolism associated with antecedent testosterone or estro... - 0 views

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    Testosterone use in men with PE is rare: 5% in this study and 1.2% in previous study by same authors. Procoagulant thrombophilia is rare, yet the authors still suggested procoagulant tests prior to Testosterone therapy in men, Estrogen therapy in women and oral birth control in women.
Nathan Goodyear

Testosterone, thrombophilia, throm... [Blood Coagul Fibrinolysis. 2014] - PubMed - NCBI - 0 views

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    This study's conclusion is to evaluate clotting factor i.e. factor V leiden, Factor VIII, and prothrombin prior to giving Testosterone.  This small study found increased clotting in some men on Testosterone. The problem here is the dosing of Testosterone in these men was 50-160 mg.  Physiologic dosing is 5-10 mg.  The problem is doping.  One wonders if physiologic dosing was undertaken if any of the men in this study would develop clotting problems, even though they had undiagnosed hypercoagulabitliy.
Nathan Goodyear

Testosterone therapy, thrombosis, thrombophilia, ... [Metabolism. 2014] - PubMed - NCBI - 0 views

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    Only abstract available here.  I can't find the full print.  For some, there is inherent thrombosis risk with Testosterone. HOWEVER, it is due to metabolism of Testosterone i.e. aromatase activity, and to supra physiologic dosing that is prevalent through the medical community.  For those with pre-existing cardiovascular disease, a full biochemical evaluation of cardiovascular risk must be undertaken prior to the initiation of Testosterone therapy.  
Nathan Goodyear

Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunolog... - 0 views

  • NK cells have been the cells most extensively studied, primarily because they constitute the predominant leukocyte population present in the endometrium at the time of implantation and in early pregnancy
  • parental chromosomal abnormalities, uterine anatomic anomalies, endometrial infections, endocrine etiologies (luteal phase defect, thyroid dysfunction, uncontrolled diabetes mellitus), antiphospholipid syndrome, inherited thrombophilias, and alloimmune causes
  • estrogen
  • ...28 more annotations...
  • progesterone
  • prolactin
  • In summary, in vivo animal experiments have shown an inhibitory role of estrogen on peripheral NK cell lytic activity, which is partly due to suppression of NK cell output by the bone marrow and partly due to suppression of individual NK cell cytotoxicity. However, in vitro studies so far have failed to show conclusively a direct effect of estrogen on NK cells.
  • At the progesterone concentrations believed to be present in the uterus [up to 10−5 m at the maternal-fetal interface (35)], studies consistently show inhibition of lymphocyte proliferation (33) and inhibition of NK cytolytic activity in vitro
  • The exact role of prolactin in NK cell regulation is unknown.
  • The overall effects of estrogen on NK cells are likely multifactorial, therefore, and depend on the type of cell affected as well as the kind of ER expressed by that cell.
  • It is known that progesterone can directly affect T cell differentiation in vitro, suppressing development of the Th1 pathway and enhancing differentiation along the Th2 pathway (44)
  • Th1 cells predominantly produce interferon-γ (IFN-γ), IL-2, and TNF-β and are involved in cell-mediated immunity. Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and stimulate humoral immunity
  • Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
  • A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
  • NK cell function is mainly regulated by IL-2 and IFN-γ
  • IL-2 causes both NK cell proliferation and enhanced cytotoxicity. IFN-γ augments NK cytolytic activity, but does not cause NK proliferation. The two cytokines act synergistically to augment NK cytotoxicity (6).
  • The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
  • there is a significant increase in the number of uNK cells throughout the secretory phase, which peaks in early pregnancy when uNK cells comprise about 75% of uterine leukocytes (62)
  • Second, uNK cell phenotype changes during the normal menstrual cycle and early pregnancy (68)
  • general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
  • The mechanism of such a progesterone-induced local immunosuppression is unclear.
  • progesterone plays an important role in proliferation and differentiation of uNK cells (32).
  • Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
  • The mechanism of this increase in uNK cell numbers has been addressed in both human and mouse models, and is likely the result of: 1) recruitment of peripheral NK cells to the uterus, and 2) proliferation of existing uNK cells
  • prolactin system plays an important role in implantation and the maintenance of pregnancy
  • the exact pathways of hormonal regulation of NK cells remain to be delineated.
  • The exact function of uNK cells has not yet been unequivocally determined
  • uNK cells express a different cytokine profile, compared with resting peripheral NK cells. mRNAs for granulocyte CSF, M-CSF, GM-CSF, TNF-α, IFN-γ, TGF-β, and leukemia inhibitory factor (LIF) have been found in decidual CD56+ cells
  • Their increased numbers in early pregnancy, their hormonal dependence, and their close proximity to the infiltrating trophoblast all suggest that they play an important role in the regulation of the maternal immune response to the fetal allograft and the control of trophoblast growth and invasion during human pregnancy
  • role of uNK cell-derived cytokines on trophoblast growth and differentiation (114, 115, 116, 117).
  • Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
  • RPL is associated with Th1 immunity, for which NK cells are partly responsible.
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    dysregulated immune system plays role in recurrent miscarriage.  Specifically, this article discusses natural killer cells (NK).
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