Simultaneous quantitation of multiple contraceptive hormones in human serum by LC–MS/MS

Blue, Steven W.; Winchell, Andrea J.; Kaucher, Amy V.; Lieberman, Rachel; Gilles, Christopher T.; Pyra, Maria; Heffron, Renee; Hou, Xuanlin; Coombs, Robert W.; Nanda, Kavita; Davis, Nicole L.; Kourtis, Athena P.; Herbeck, Joshua T.; Baeten, Jared M.; Lingappa, Jairam R.; Erikson, David W.

doi:10.1016/j.contraception.2018.01.015

Cited by 46 publications

(33 citation statements)

References 20 publications

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“…Where indicated, cells collected by vaginal lavage were stained with crystal violet to identify wild-type and NSG mice in the estrus stage of the estrous cycle (26). Also as indicated, mice were euthanized 24 h after the fifth NET-EN treatment, and the serum was sent to the Endocrine Technologies Support Core at the Oregon National Primate Research Center to quantify norethisterone (NET) levels by liquid chromatography-tandem triple quadrupole mass spectrometry (27).…”

Section: Methodsmentioning

confidence: 99%

Norethisterone Enanthate Increases Mouse Susceptibility to Genital Infection with Herpes Simplex Virus Type 2 and HIV Type 1

et al. 2020

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Norethisterone enanthate (NET-EN) and depot-medroxyprogesterone acetate (DMPA) are two forms of injectable progestin used for contraception. Whereas clinical research indicates that women using DMPA are more susceptible to HIV and other genital pathogens, causal relationships have not been determined. Providing an underlying mechanism for this connection, however, is recent work that showed DMPA weakens genital mucosal barrier function in mice and humans and respectively promotes susceptibility of wild-type and humanized mice to genital infection with HSV type 2 and HIV type 1. However, analogous effects of NET-EN treatment on antivirus immunity and host susceptibility to genital infection are much less explored. In this study, we show that compared with mice in estrus, treatment of mice with DMPA or NET-EN significantly decreased genital levels of the cell-cell adhesion molecule desmoglein-1 and increased genital mucosal permeability. These effects, however, were more pronounced in DMPA-versus NET-ENtreated mice. Likewise, we detected comparable mortality rates in DMPA-and NET-ENtreated wild-type and humanized mice after intravaginal infection with HSV type 2 or cell-associated HIV type 1, respectively, but NET-EN treatment was associated with slower onset of HSV-induced genital pathology and lower burden of systemic HIV disease. These findings reveal DMPA and NET-EN treatment of mice significantly reduces genital desmoglein-1 levels and increases genital mucosal permeability and susceptibility to genital pathogens while also implying that NET-EN generates less compromise of genital mucosal barrier function than DMPA. ImmunoHorizons, 2020, 4: 72-81.

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Section: Methodsmentioning

confidence: 99%

Norethisterone Enanthate Increases Mouse Susceptibility to Genital Infection with Herpes Simplex Virus Type 2 and HIV Type 1

et al. 2020

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“…However, Shenouda et al also found that serum immunoassays did not detect estrogen or progesterone in samples from OC users above that observed in men or women in the early follicular phase of the menstrual cycle. Thus, we further recommend that future studies involving OC users should include high-performance liquid chromatography analysis of all analogs of estrogen and progesterone (both endogenous and pharmaceutical), as developed recently (Blue et al, 2018).…”

Section: Limitationsmentioning

confidence: 99%

Oral contraceptives and menstrual cycle influence autonomic reflex function

et al. 2020

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Progesterone and its analogues are known to influence ventilation. Therefore, the purpose of this study was to investigate the role of endogenous and pharmaceutical female sex hormones in ventilatory control during the activation of the metaboreflex, mechanoreflex, and CO2 chemoreflex. Women aged 18–30 taking (n = 14) or not taking (n = 12) oral contraceptives (OC and NOC, respectively) were tested in the low hormone (LH) and high hormone (HH) conditions corresponding to the early follicular and mid‐luteal phases (NOC) or placebo and high‐dose pills (OC). Women underwent three randomized trials: (a) 3 min of passive leg movement (PLM), (b) 2 min of 40% maximal voluntary handgrip exercise followed by 2 min of post‐exercise circulatory occlusion (PECO), and (c) 5 min of breathing 5% CO2. We primarily measured hemodynamics and ventilation. During PLM, the OC group had a smaller pressor response (p = .012). During PECO, the OC group similarly exhibited a smaller pressor response (p = .043) and also exhibited a greater ventilatory response (p = .024). Lastly, in response to breathing 5% CO2, women in the HH phase had a greater ventilatory response (p = .022). We found that OC use attenuates the pressor response to both the metaboreflex and mechanoreflex while increasing the ventilatory response to metaboreflex activation. We also found evidence of an enhanced CO2 chemoreflex in the HH phase. We hypothesize that OC effects are from the chronic upregulation of pulmonary and vascular β‐adrenergic receptors. We further suggest that the increased cyclic progesterone in the HH phase enhances the chemoreflex.

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“…Differences across studies may be impacted by differences in study design, including numbers of women investigated, women's demographic characteristics (ethnicity, race, body mass index, weight and metabolism), number of injections, injection sites, and time and frequency of measurements [14] , [19] . Assay methodologies to measure progestins have evolved over time to be more sensitive and specific; however, this can further complicate interpretation when comparing data from newer and older studies [20] , [21] , [22] . Because of the pharmacokinetics of the formulations, serum concentrations of MPA and NET in the first weeks following injection of DMPA-IM and NET-EN, respectively, exceed contraceptive efficacy but are necessary to ensure maintenance of contraceptive efficacy throughout the dosing duration.…”

Section: Pharmacologic Biologic and Epidemiologic Studies Of Dmpa Anmentioning

confidence: 99%

Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

et al. 2019

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Access to safe and effective contraceptive choices is a reproductive right and contributes tremendously to improvements in maternal and child health. Progestin-only injectables, particularly intramuscularly injected depot medroxyprogesterone acetate (DMPA-IM), have received increased attention given findings suggesting a potential association with increased HIV risk. For women at high risk of HIV, the World Health Organization's Medical eligibility criteria for contraceptive use currently aggregate recommendations for all progestin-only injectables, including DMPA-IM, subcutaneously injected DMPA (DMPA-SC) and intramuscularly injected norethindrone/ norethisterone enanthate (NET-EN), except in the case of some drug interactions. We considered whether published data indicate differences or similarities between these injectables relevant to risk of acquiring HIV. In vitro data confirm different biological activities of these distinct progestins, including that MPA, and not NET, binds and activates the glucocorticoid receptor resulting in different biological effects relevant to immune function. Limited clinical data suggest changes in immunologic activity following DMPA-IM and NET-EN initiation, but interstudy variation and study design differences diminish ability to determine clinical relevance and the degree to which DMPA-IM and NET-EN could act differentially. The highest-quality epidemiologic studies suggest a potential 40% increase in HIV incidence in users of DMPA-IM relative to women not using hormonal contraception but no significant increase in risk in users of NET-EN. In our opinion, most of the available biologic activity and epidemiologic data indicate that DMPA and NET-EN are likely to act differently, and data remain too limited to evaluate differences between DMPA-IM and DMPA-SC.

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Simultaneous quantitation of multiple contraceptive hormones in human serum by LC–MS/MS

Abstract: This analytical method can be used for quantitating contraceptive steroid levels in women for monitoring systemic exposure to determine drug interactions, nonadherence, misreporting and proper dosing.

Cited by 46 publications

References 20 publications

Norethisterone Enanthate Increases Mouse Susceptibility to Genital Infection with Herpes Simplex Virus Type 2 and HIV Type 1

Norethisterone Enanthate Increases Mouse Susceptibility to Genital Infection with Herpes Simplex Virus Type 2 and HIV Type 1

Oral contraceptives and menstrual cycle influence autonomic reflex function

Pharmacokinetic, biologic and epidemiologic differences in MPA- and NET-based progestin-only injectable contraceptives relative to the potential impact on HIV acquisition in women

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