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      Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms

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      1 , 2 , , 3 , 4 , 5 , 6
      Endocrine Reviews
      Endocrine Society

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          Abstract

          Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition, concentration of the progestin component, frequency of dosage, and method of administration, is currently available globally. However, the options are rather limited in settings with restricted economic resources that frequently overlap with areas of high HIV-1 prevalence. The predominant contraceptive used in sub-Saharan Africa is the progestin-only three-monthly injectable depot medroxyprogesterone acetate. Determination of whether HCs affect HIV-1 acquisition has been hampered by behavioral differences potentially confounding clinical observational data. Meta-analysis of these studies shows a significant association between depot medroxyprogesterone acetate use and increased risk of HIV-1 acquisition, raising important concerns. No association was found for combined oral contraceptives containing levonorgestrel, nor for the two-monthly injectable contraceptive norethisterone enanthate, although data for norethisterone enanthate are limited. Susceptibility to HIV-1 and other sexually transmitted infections may, however, be dependent on the type of progestin present in the formulation. Several underlying biological mechanisms that may mediate the effect of HCs on HIV-1 and other sexually transmitted infection acquisition have been identified in clinical, animal, and ex vivo studies. A substantial gap exists in the translation of basic research into clinical practice and public health policy. To bridge this gap, we review the current knowledge of underlying mechanisms and biological effects of commonly used progestins. The review sheds light on issues critical for an informed choice of progestins for the identification of safe, effective, acceptable, and affordable contraceptive methods.

          Abstract

          Review of clinical, animal, and ex vivo data on mechanisms whereby hormonal contraception may increase HIV-1 acquisition reveals evidence for several plausible biological mechanisms for medroxyprogesterone acetate.

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          Most cited references348

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          The complex role of estrogens in inflammation.

          There is still an unresolved paradox with respect to the immunomodulating role of estrogens. On one side, we recognize inhibition of bone resorption and suppression of inflammation in several animal models of chronic inflammatory diseases. On the other hand, we realize the immunosupportive role of estrogens in trauma/sepsis and the proinflammatory effects in some chronic autoimmune diseases in humans. This review examines possible causes for this paradox. This review delineates how the effects of estrogens are dependent on criteria such as: 1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses (e.g., T cell inhibited by estrogens vs. activation of B cell); 2) the cell types involved during different phases of the disease; 3) the target organ with its specific microenvironment; 4) timing of 17beta-estradiol administration in relation to the disease course (and the reproductive status of a woman); 5) the concentration of estrogens; 6) the variability in expression of estrogen receptor alpha and beta depending on the microenvironment and the cell type; and 7) intracellular metabolism of estrogens leading to important biologically active metabolites with quite different anti- and proinflammatory function. Also mentioned are systemic supersystems such as the hypothalamic-pituitary-adrenal axis, the sensory nervous system, and the sympathetic nervous system and how they are influenced by estrogens. This review reinforces the concept that estrogens have antiinflammatory but also proinflammatory roles depending on above-mentioned criteria. It also explains that a uniform concept as to the action of estrogens cannot be found for all inflammatory diseases due to the enormous variable responses of immune and repair systems.
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            The nature of the principal type 1 interferon-producing cells in human blood.

            Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
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              Probiotics and the gut microbiota in intestinal health and disease.

              The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases. While a growing number of well-conducted, prospective, randomized, controlled, clinical trials are emerging and investigations of underlying mechanisms of action are being undertaken, questions remain with respect to the specific immune and physiological effects of probiotics in health and disease. This Review considers recent advances in clinical trials of probiotics for intestinal disorders in both adult and pediatric populations. An overview of recent in vitro and in vivo research related to potential mechanisms of action of various probiotic formulations is also considered.
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                Author and article information

                Journal
                Endocr Rev
                Endocr. Rev
                edrv
                edrv
                Endocrine Reviews
                Endocrine Society (Washington, DC )
                0163-769X
                1945-7189
                04 January 2018
                February 2018
                04 January 2018
                : 39
                : 1
                : 36-78
                Affiliations
                [1 ]Department of Molecular and Cell Biology, University of Cape Town, Cape Town 7700, South Africa
                [2 ]Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7925, South Africa
                [3 ]Department of Pathology and Molecular Medicine, McMaster University, Ontario L8S 4K1, Canada
                [4 ]McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8S 4K1, Canada
                [5 ]Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294
                [6 ]Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama 35294
                Author notes
                Correspondence and Reprint Requests:  Janet P. Hapgood, PhD, Department of Molecular and Cell Biology, University of Cape Town, University Avenue, Rondebosch 7700, Western Province, South Africa. E-mail: Janet.Hapgood@ 123456uct.ac.za .
                Article
                edrv_201700103
                10.1210/er.2017-00103
                5807094
                29309550
                45c47f33-07ba-40c8-a5c7-0a760ed7b756
                Copyright © 2018 Endocrine Society

                This article has been published under the terms of the Creative Commons Attribute License (CC BY; https://creativecommons.org/licenses/by/4.0/).

                History
                : 02 May 2017
                : 27 November 2017
                Page count
                Figures: 4, Tables: 6, Equations: 0, References: 380, Pages: 43
                Categories
                Reviews
                Reproductive Biology and Sex-Based Medicine
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