Browsing by Subject "Levonorgestrel"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Cervical and systemic concentrations of long acting hormonal contraceptive (LARC) progestins depend on delivery method: Implications for the study of HIV transmission.
    (PloS one, 2019-01) Buckner, Lyndsey R; Drobnis, Erma Z; Augustine, Molly S; Rogers, Lynette K; Akers, Jill; Mott, Patricia D; Hope, Thomas J; Quayle, Alison J; Schust, Danny J
    Progestin-only long-acting reversible contraceptives (LARCs) are increasingly popular among women seeking contraception; however, recent epidemiological studies suggest that systemically administered medroxyprogesterone acetate (MPA) may increase HIV acquisition. In order to determine the exact mechanisms underlying increases in transmission specific to MPA use and to test safer, alternative contraceptive progestin types and delivery methods, in vitro modeling studies must be performed. To achieve this, it is imperative that accurate hormone concentrations be utilized when modeling progestin-mediated outcomes, as the down-stream effects are dose-dependent. The local concentrations of progestins to which the lower female genital tract tissues are exposed after initiation of LARCs are unknown, but they likely differ from peripheral concentrations, dependent upon the progestin type and delivery method. Here, we measured in vivo endocervical and plasma concentrations of (1) systemically-delivered depo MPA (DMPA), (2) levonorgestrel (LNG) delivered via intrauterine system (IUS) and (3) etonogestrel (ETG) delivered via vaginal ring in women who recently initiated contraception treatment. Levels of ETG and LNG in cervical secretions were 100-200 fold higher than plasma levels. In contrast, measurable MPA levels were approximately 10-fold higher in plasma compared to cervical secretions. These results will inform the design of accurate in vitro studies on the influence of progestins on epithelial cells, tissue explants, and peripheral blood cells, to be able to better predict in vivo outcomes. Subsequent observations will aid in determining how MPA might influence HIV acquisition and may facilitate identification of optimal progestin-containing LARC alternatives for women at high risk for HIV infection.
  • Thumbnail Image
    ItemOpen Access
    Effects of three long-acting reversible contraceptive methods on HIV target cells in the human uterine cervix and peripheral blood.
    (Reproductive biology and endocrinology : RB&E, 2019-02) Li, Liping; Zhou, Jie; Wang, Weijia; Huang, Lina; Tu, Jiaoqin; Baiamonte, Lyndsey; Stark, Moselle; Mills, Mistie; Hope, Thomas J; Drobnis, Erma Z; Quayle, Alison J; Schust, Danny J

    Background

    Hormonal contraceptives, particularly depot medroxyprogesterone acetate (DMPA), have been reported to be associated with substantially enhanced HIV acquisition; however, the biological mechanisms of this risk remain poorly understood. We aimed to investigate the effects of different hormonal contraceptives on the expression of the HIV co-receptors, CXCR4 and CCR5, on female endocervical and peripheral blood T cells.

    Methods

    A total of 59 HIV-negative women were enrolled, including 15 initiating DMPA, 28 initiating a levonorgestrel-releasing intrauterine device (LNG-IUD) and 16 initiating an etonogestrel (ETG)-delivering vaginal ring. Peripheral blood and endocervical cytobrush specimens were collected at enrollment and 3-4 weeks after contraception initiation to analyze the expression of CXCR4 and CCR5, on CD4+ and CD8+ T cells using flow cytometry.

    Results

    Administration of DMPA increased the percentages of CD4+ and CD8+ T cells expressing CCR5 in the endocervix but not in the peripheral blood. Administration of the LNG-IUD or the ETG vaginal ring did not affect the percentages of T lymphocytes expressing CXCR4 or CCR5 in the female cervix or peripheral blood.

    Conclusions

    Increase in the percentage of endocervical T cells expressing CCR5 upon DMPA exposure provides a plausible biological explanation for the association between DMPA use and an elevated risk of HIV infection.