A multicenter study of levonorgestrel—Estradiol contraceptive vaginal rings I — Use effectiveness

Sivin, Irving; Mishell, Daniel R.; Victor, Arne; Dı́az, Soledad; Alvarez-Sanchez, Francisco; Nielsen, Niels Chr.; Akinla, Oladele; Pyörälä, Tapani; Coutinho, Elsimar Metzker; Faúndes, Aníbal; Roy, Subir; Brenner, Paul F.; Ahren, Tom; Pavéz, Margarita; Brache, Vivian; Giwa-Osagie, O.F.; Fasan, Margaret O.; Zausner-Guelman, Belinha; Darze, Elias; daSilva, Jose Carlos Gama; Dı́az, Juan; Jackanicz, Theodore M.; Stern, Janet; Nash, Harold A.

doi:10.1016/0010-7824(81)90003-2

Cited by 58 publications

(21 citation statements)

References 4 publications

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“…In addition, the secretions were evaluated by cultivation on broad-spectrum media for aerobic and anaerobic microbes and a selective media for mycoses, Trichomonas vaginalis , and Neiserria spp. In the early 1980s, Population Council reservoir-IVRs (Jackanicz, 1981) delivering the contraceptive levonorgestrel (LNG) in combination with estradiol (E2) were studied for contraceptive effectiveness and acceptability in multicentered trials involving 1,103 ring users (Sivin et al, 1981a). Increased vaginal discharge, potentially due to alteration of the vaginal microbiome, was identified as the most frequently voiced complaint by users (Sivin et al, 1981a, b).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the vaginal microbial communities in women with recurrent genital HSV receiving acyclovir intravaginal rings

et al. 2014

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Vaginally administered antiviral agents may reduce the risk of HIV and HSV acquisition. Delivery of these drugs using intravaginal rings (IVRs) holds the potential benefits of improving adherence and decreasing systemic exposure, while maintaining steady-state drug levels in the vaginal tract. Elucidating how IVRs interact with the vaginal microbiome constitutes a critical step in evaluating the safety of these devices, as shifts the vaginal microbiome have been linked with several disease states. To date, clinical IVR trials have relied on culture-dependent methods that omit the high diversity of unculturable microbial population. Longitudinal, culture-independent characterization of the microbiota in vaginal samples from 6 women with recurrent genital HSV who used an acyclovir IVR was carried out and compared to the communities developing in biofilms on the IVR surface. The analysis utilized Illumina MiSeq sequence datasets generated from bar-coded amplicons of 16S rRNA gene fragments. Specific taxa in the vaginal communities of the study participants were found to be associated with the duration of recurrent genital HSV status and the number of HSV outbreaks. Taxonomic comparison of the vaginal and IVR biofilm communities did not reveal any significant differences, suggesting that the IVRs were not systematically enriched with members of the vaginal microbiome. Device usage did not alter the participants' vaginal microbial communities, within the confines of the current study design. Rigorous, molecular analysis of the effects of intravaginal devices on the corresponding microbial communities shows promise for integration with traditional approaches in the clinical evaluation of candidate products.

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Section: Discussionmentioning

confidence: 99%

Comparison of the vaginal microbial communities in women with recurrent genital HSV receiving acyclovir intravaginal rings

et al. 2014

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“…These rings were then compared with a 150/zg L-NOG and 30 #g EE oral preparation. The results of this trial [15] indicated little difference in pregnancy rate (2 per HWY) or continuation rate of 50%. The ring users discontinued because of complaints of vaginal symptoms in higher numbers than the pill users, whereas the latter discontinued for systemic symptoms such as nausea, dizziness and headaches.…”

Section: Combined Estrogen and Progestogen Releasing Ringsmentioning

confidence: 70%

Present status of contraceptive vaginal rings

et al. 1990

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The first review documenting the fact that drugs and toxic substances could be absorbed through the vaginal epithelium was published by Macht in 1918 [1]. Greenblatt in 1954 [2] demonstrated therapeutic plasma levels of progesterone following vaginal administration. It was the demonstration by Dziuk and Cook in 1965 [3] that steroids when placed in Silastic tubes or discs were subject to constant release rates, that paved the way for vaginal delivery of contraceptive steroid to become a reality.The vaginal route of administration has a number of advantages:(1) Avoidance of the gastrointestinal tract, res~ting in a speedy distribution throughout the circulatory system, thereby avoiding the first pass effect of the liver.(2) Continuous release of the active compound with the potential of using lower doses, hence attracting fewer side effects.(3) Once the contraceptive device is in place, daily attention is not required, thus patient compliance should be increased, enhancing theoretical effectiveness and use effectiveness.The contraceptive effect is unrelated to the act of intercourse.(5) The possibility of self-administration allows control of contraception to remain with the patient.In 1970 Mishell et al.[4] published studies on vaginal rings using medroxyprogesterone acetate mixed with Silastic to form a 70-80 mm homogeneous ring. He demonstrated that ovulation could be inhibited by such a delivery system. However, the assumption that the progestogen had been delivered in a constant and even fashion was unsupported. In vitro studies showed that these rings exhibited a 'burst release', i.e. there was a high initial delivery of this steroid followed by a rapid decline, which would have little advantage over the injectable administration of this agent.

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“…Despite the estrogen, breakthrough bleeding remains a problem. About 7±8% of women discontinued the rings because of menstrual problems, compared with 4% of oral contraceptive users [59]. Vaginal problems -particularly vaginitis, leukorrhea, and other discharge, were significantly more common among women using rings than among OC users.…”

Section: Combined Levonorgestrel-estradiol Vaginal Ringsmentioning

confidence: 99%