Differential Glucocorticoid Receptor‐Mediated Effects on Immunomodulatory Gene Expression by Progestin Contraceptives: Implications for <scp>HIV</scp>‐1 Pathogenesis

Hapgood, Janet P.; Ray, Roslyn M.; Govender, Yashini; Avenant, Chanel; Tomasicchio, Michele

doi:10.1111/aji.12214

Cited by 33 publications

(44 citation statements)

References 43 publications

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“…Studies using non-human primate models demonstrated that DMPA enhances the risk of simian immunodeficiency virus (SIV) acquisition via vaginal exposure (reviewed in 7,13 ). Medroxyprogesterone acetate (MPA), the contraceptive component of DMPA, was shown to suppress systemic regulators of cellular and humoral immunity, reduce cytokine production by plasmacytoid dendritic cells (pDCs), and increase the replication of HIV-1 in activated peripheral blood mononuclear cells (PBMCs) in vitro 28-32 .…”

Section: Introductionmentioning

confidence: 99%

Effect of Hormonal Contraception on the Function of Plasmacytoid Dendritic Cells and Distribution of Immune Cell Populations in the Female Reproductive Tract

Michel¹,

Huijbregts²,

Gleason

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective Epidemiological evidence suggests an association between the use of hormonal contraception and an increased risk of acquiring sexually transmitted diseases including HIV-1. We sought to elucidate the biological mechanisms underlying the effect of hormonal contraception on the immune system. Design Cross-sectional study. Methods To delineate the biological mechanisms underlying the effect of hormonal contraceptives on the immune system, we analyzed the functional capacity of circulating plasmacytoid dendritic cells (pDCs), the distribution of vaginal immune cell populations, and the systemic and genital levels of immune mediators in women using depot medroxyprogesterone acetate (DMPA), NuvaRing, or combined oral contraceptives (COC). Results The use of DMPA or NuvaRing was associated with reduced capacity of circulating pDCs to produce IFNα and TNFα in response to TLR-9 stimulation. Systemic levels of IFNα and cervicovaginal fluid levels of IFNα, CXCL10, MCP-1, and G-CSF were significantly lower in DMPA users compared to control volunteers not using hormonal contraception. The density of CD207+ Langerhans cells in the vaginal epithelium was reduced in NuvaRing and COC users but not in DMPA users. Conclusions The presented evidence suggests that the use of some types of hormonal contraception is associated with reduced functional capacity of circulating pDCs and altered immune environment in the female reproductive tract.

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Section: Introductionmentioning

confidence: 99%

Effect of Hormonal Contraception on the Function of Plasmacytoid Dendritic Cells and Distribution of Immune Cell Populations in the Female Reproductive Tract

Michel¹,

Huijbregts²,

Gleason

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Medroxyprogesterone (MPA), for example, has androgenic activity, no anti-mineralocorticoid activity and potent glucocorticoid activity, higher than any other progestogen or endogenous progesterone. Activation of glucocorticoid receptors, seen with MPA, may influence glucocorticoid-like immunosuppressive effects on genes involved with immune function [86, 87]. These differences between contraceptives warrant further investigation and may influence relative contraceptive safety.…”

Section: Potential Biologic Mechanisms For Increased Hiv Acquisition mentioning

confidence: 99%

Contraceptive Methods and Risk of HIV Acquisition or Female-to-Male Transmission

et al. 2014

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Effective family planning with modern contraception is an important intervention to prevent unintended pregnancies which also provides personal, familial, and societal benefits. Contraception is also the most cost-effective strategy to reduce the burden of mother-to-child HIV transmission for women living with HIV who wish to prevent pregnancy. There are concerns, however, that certain contraceptive methods, in particular the injectable contraceptive depot medroxyprogesterone acetate (DMPA), may increase a woman's risk of acquiring HIV or transmitting it to uninfected males. These concerns, if confirmed, could potentially have large public health implications. This paper briefly reviews the literature on use of contraception among women living with HIV or at high risk of HIV infection. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommendations place no restrictions on the use of hormonal contraceptive methods by women with or at high risk of HIV infection, although a clarification recommends that, given uncertainty in the current literature, women at high risk of HIV who choose progestogen-only injectable contraceptives should be informed that it may or may not increase their risk of HIV acquisition and should also be informed about and have access to HIV preventive measures, including male or female condoms.

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“…Further studies are needed for a better comprehension of the many and complex effects of progesterone and other steroid hormones on melanoma and other cancers. This need is made urgent especially when considering that progesterone and its synthetic progestin analogs are clinically employed as methods of contraception and in hormone replacement therapies [42][43][44][45][46][47], in the treatment of recurrent miscarriage and during assisted reproductive technologies [48]. A higher caution in the clinical use of progesterone is thus mandatory, since PG concentrations capable of stimulating melanoma cell proliferation are very close to the pharmacological doses of PG commonly used in a wide spectrum of physio-pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

Progesterone and Melanoma Cells: An Old Story Suspended between Life and Death

Francesca¹,

Gabriella²

2015

J Steroids Hormon Sci

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IntroductionSteroid hormones regulate cell proliferation, survival and development and have been involved in the origin and/or progression of cancer [1][2][3][4][5][6]. In the last decades, many epidemiological and experimental studies have suggested that steroid hormones may be etiologic factors in tumor generation, but whereas for some tumors, the link between hormones and cancer is well established, in other cases the relationship is not fully defined or even contradictory [1,[7][8][9].Many human cancers, especially those of reproductive tissues, depend on progesterone (PG) [9]. PG is known to participate in the regulation of several physiological and pathological processes in mammals, such as ovarian function, growth and differentiation of the uterine endometrium and mammary gland [10]. However, PG also participates in non-reproductive processes, such as neural excitability, learning and memory, and in pathological processes like cancer [10][11][12]. In literature, however, data exploring the relationship between progesterone and cancer are controversial. One of the main problems lies in the fact that depending on the cell type, hormonal environment, growth conditions, and developmental stage, progesterone can either stimulate or inhibit cell proliferation or promote cell differentiation [13]. It has been reported that the lifetime exposure to reproductive hormones, in particular progesterone and/or estrogens, affects the risk of breast cancer and melanoma [12]. Melanoma is a widespread skin cancer with very poor prognosis. It is an old story, however still debated, that the outcome of established melanoma is influenced by endocrine status although the acquisition of melanoma does not seem to be influenced by female sex hormones [14,15]. Early studies showed that female patients with malignant melanoma had some survival advantage [16], which in some studies was observed in preas opposed to post-menopausal women [17][18][19]. Others larger multivariate analyses, however, demonstrated that it was equally strong in pre-as well as in post-menopausal groups [20]. Parallely, the literature concerning melanoma progression in pregnancy is also controversial [21][22][23][24], although several recent reports demonstrate that pregnancyassociated melanomas have poorer outcomes than other melanomas [25][26][27][28][29].In vitro progesterone influences melanoma growth [30][31][32][33], but several melanoma cell lines have been studied and very different experimental protocols have been used, so that the results actually available in literature are not univocal. Further research on this topic is thus needed, especially in view of the widespread use of PG in clinical practice. In this study, we report the results obtained by testing in vitro the effects of a wide range of concentrations of PG on the growth and viability of human melanoma cells. Materials and methods Cell Culture and TreatmentsThe human melanoma A-375 cell line was purchased from the American Type Culture Collection (ATCC, Rockville, MD) and grown in DMEM su...

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Differential Glucocorticoid Receptor‐Mediated Effects on Immunomodulatory Gene Expression by Progestin Contraceptives: Implications for HIV‐1 Pathogenesis

Cited by 33 publications

References 43 publications

Effect of Hormonal Contraception on the Function of Plasmacytoid Dendritic Cells and Distribution of Immune Cell Populations in the Female Reproductive Tract

Effect of Hormonal Contraception on the Function of Plasmacytoid Dendritic Cells and Distribution of Immune Cell Populations in the Female Reproductive Tract

Contraceptive Methods and Risk of HIV Acquisition or Female-to-Male Transmission

Progesterone and Melanoma Cells: An Old Story Suspended between Life and Death

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