Vaginal Ring Research Articles

Contraceptive plans and purchase after an induced abortion: A nationwide register study from Finland

ObjectivesTo examine the types of hormonal contraceptive methods chosen at the time of the abortion, and how they correspond to post-abortion hormonal contraceptive purchase. Study designThis was a prospective register-based study. We identified the present cohort of 8428 women undergoing induced abortion between July 1, 2017 and December 31, 2018, using the Prescription Centre, Social Insurance Institution database and the Finnish National Register of Induced Abortions. From the Register of Induced Abortions, we gathered information on planned post-abortion contraception. The redeemed prescriptions of hormonal contraception were identified from the Prescription Centre until December 31, 2019. We analyzed the hormonal contraceptive methods planned at the time of the abortion, and how they corresponded to hormonal contraceptive purchase during the 1-year follow-up. We also assessed factors (age, socioeconomic status, education, civil status, and reproductive history) affecting post-abortion contraceptive purchase by using Poisson regression models. ResultsAt the time of the abortion, 83% (n = 7023) of the women were planning to start using hormonal contraception. Planning any hormonal contraception at the time of the abortion was associated with a higher probability to purchase hormonal contraception after the abortion (incidence rate ratio [IRR] 2.30, 95% confidence intervals [CI] 2.07–2.55), especially in cases of the vaginal ring (IRR 42.66, 95% CI 33.89–53.71) and contraceptive patch (IRR 156.33, 95% CI 111.31–219.55). The following variables were associated with lower incidence rates for purchasing hormonal contraception after the abortion: educational level of bachelor at the highest or missing information on education, civil status as married or divorced, and history of delivery or induced abortion. ConclusionsThe majority of women undergoing abortion plan to use hormonal contraceptive method for post-abortion contraception. Planning any hormonal contraceptive method at the time of an induced abortion is an important predictor of purchasing the method within the year after the abortion. ImplicationsHormonal contraceptive purchase after an abortion is associated with pre-abortion contraceptive planning. Many background factors for not purchasing hormonal contraception can be identified, which may guide counseling dedicated to these groups.

Vaginal Cancer: Association with long term use of Pessary in Pelvic Organ Prolapse

Vaginal cancer, rarest form of gynaecological cancer (0.6%) has been found to be associated with long term use of vaginal ring pessary, which have long been used in alternative management of pelvic organ prolapse (POP) other than surgery. A through survey was done in remote areas of Cox’s bazar, refugee camp where out of 52 cases of pelvic organ prolapse, 7 cases found to use vaginal ring pessary for long and out of 7, vaginal cancer developed in 4 cases. All of them were aged women above 60 and had defaulted follow up presented with vaginal bleeding, varying discharge and pain of varying intensity. One patient had only local lesion was treated by surgical removal followed by radiotherapy. The 2 nd one, 68 years, received neo-adjuvant therapy and died before planned surgery. The 3 rd one, aged 79, did not come for follow up after diagnosis of vaginal cancer done and advised for definitive surgical treatment, family refused operation and she passed away after 2 years at 81 years. The 4 th one declined further investigations and any form of treatment once diagnosed with vaginal cancer. So, all patients of pelvic organ prolapse should be informed thoroughly (both verbal and written informed consent) before inserting pessary for potential long term serious consequences where strict compliance must be ensured for subsequent regular follow up and biopsy should be mandatory for any suspicious chronic vaginal ulcers among them. Bangladesh J Obstet Gynaecol, 2022; Vol. 37(1): 75-77

Women’s motivations for participating in the dapivirine vaginal ring open label extension study

ABSTRACT Open-Label Extension (OLE) studies are important in the drug development process and are used to further support the licensing applications and regulatory approvals of products. We aimed to understand why women chose to join the HOPE OLE study – where women were offered the dapivirine vaginal ring after two pivotal trials were completed – through data collected from individual in-depth interviews. Ten women at each of the six HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were enrolled (n = 60). Access to an effective user-initiated HIV prevention product was one of the main reasons women joined HOPE. Although many participants worried that their male partners might expose them to HIV, they chose to remain in their relationships and avoid conflict or confrontation with their partners by discreetly using the ring to protect themselves. Other reasons for joining were quality healthcare, reimbursement and altruism. Researchers should better understand social and personal motivators behind research participation in order to recognize community sociocultural norms and its influences on product acceptability and adherence challenges.

Three-Dimensionally Printed Vaginal Rings: Perceptions of Women and Gynecologists in a Cross-Sectional Survey.

Three-dimensional printing technologies can be implemented for the fabrication of personalized vaginal rings (VRs) as an alternative approach to traditional manufacturing. Although several studies have demonstrated the potential of additive manufacturing, there is a lack of knowledge concerning the opinions of patients and clinicians. This study aimed to investigate the perception of women and gynecologists regarding VRs with personalized shapes. The devices were printed with different designs (traditional, "Y", "M", and flat circle) by Fused Deposition Modeling for a cross-sectional survey with 155 participants. Their anticipated opinion was assessed through a questionnaire after a visual/tactile analysis of the VRs. The findings revealed that most women would feel comfortable using some of the 3D-printed VR designs and demonstrated good acceptability for the traditional and two innovative designs. However, women presented multiple preferences when the actual geometry was assessed, which directly related to their age, previous use of the vaginal route, and perception of comfort. In turn, gynecologists favored prescribing traditional and flat circle designs. Overall, although there was a difference in the perception between women and gynecologists, they had a positive opinion of the 3D-printed VRs. Finally, the personalized VRs could lead to an increase in therapeutic adherence, by meeting women's preferences.

Attitudes Toward Menstrual Suppression Among Cyclic and Continuous Contraceptive Vaginal Ring Users in Kenya.

Multipurpose prevention technologies (MPTs) are developmental dual-purpose options that would provide women with a contraceptive as well as a prevention modality aimed at sexually transmitted infections. The contraceptive vaginal ring (CVR) has many properties that makes it an ideal MPT candidate. The objective of this study is to understand women's attitudes towards menstrual suppression, a potential side effect of using a CVR, and how to address these attitudes for MPT vaginal rings in development. We analyzed data derived from a subset of cohort study participants (n=45) in Thika, Kenya between January 2016- December 2018. The primary study enrolled 121 women 18-40 years with bacterial vaginosis and randomized them to cyclic or continuous CVR use for eight months. During the 6-month follow-up, a questionnaire eliciting attitudes towards menstrual suppression was administered. Responses to the menstrual suppression questionnaire between participants in the cyclic and continuous CVR use groups were compared. Likert-scale responses were summed to create a menstrual suppression attitude summary score, and a hierarchical cluster analysis was conducted to identify similarities in response patterns among all participants. Totally 81.8% of continuous CVR users believed that one was less likely to get pregnant after using hormonal medication to suppress menses, compared to 47.8% of cyclic CVR users (P=0.02), and were more worried it would cause long-term health effects (86.4% vs 60.9%, p = 0.05). The menstrual suppression attitude summary score ranged from 8 to 42, with lower scores indicating negative attitudes. The summary score identified three distinct clusters. When asked if menstrual suppression effects long-term health; 100% of Cluster 3 was worried compared to 80.8% of Cluster 2 and 46.2% of Cluster 1 (p = 0.03). The average summary score among Cluster 3 (Mean = 14.8, SD = 4.6) was lower (p < 0.001) and women were more worried about discomfort during sex (p=0.05) as well as their sexual partners feeling the ring (p=0.02). Women are more likely to have negative attitudes if they believe menstrual suppression hinders future reproductive health. Education on cycle control and fertility could mitigate negative attitudes and improve uptake of CVRs.

Exploring the potential of dapivirine vaginal ring for HIV prevention in Namibia: a call to action

The recent recommendation by the World Health organization for the use of the dapivirine vaginal ring as a promising safe, efficacious and alternate choice for HIV prevention among women at significant risk of infection presents a welcome development for countries hard hit by HIV especially those in Sub-Saharan Africa. In Namibia, there is paucity of evidence on whether this novel HIV prevention strategy would be acceptable among those women at elevated risk of acquiring the virus. This paper provides a discourse on the opportunities and potential challenges in introducing the dapivirine vaginal ring on a large scale in the country.

Physicochemical considerations in the formulation development of silicone elastomer vaginal rings releasing 5-nitroimidazole drugs for the treatment of bacterial vaginosis

Bacterial vaginosis (BV) is a common dysbiosis of the human vaginal microbiota characterized by depletion of hydrogen peroxide and lactic acid-producing Lactobacillus bacteria and an overgrowth of certain facultative anaerobic bacteria. Although short-term cure rates following treatment with frontline antibiotics (most notably oral metronidazole (MNZ), clindamycin vaginal cream, and MNZ vaginal gel) are generally high, longer-term recurrence rates are an issue. The development of vaginal formulations offering continuous/sustained administration of antibiotic drugs over one or more weeks might prove useful in reducing recurrence. Here, we report the manufacture and preclinical testing of matrix-type vaginal rings offering sustained release of four 5-nitroimidazole antimicrobial drugs either being used clinically or having potential in treatment of BV – MNZ, tinidazole (TNZ), secnidazole (SNZ) and ornidazole (ONZ). All four drugs showed good compatibility with a medical-grade addition-cure silicone elastomer based upon thermal analysis experiments, and matrix-type rings containing 250 mg (3.125 %w/w) of each drug were successfully manufactured by reaction injection molding. 28-day in vitro drug release studies demonstrated root-time kinetics, with daily release rates of 25, 22, 9 and 6 mg/day½ for SNZ, ONZ, MNZ and TNZ, respectively. The rank order of drug release from rings correlated with the simple molecular permeability parameter S/V, where S is the measured drug solubility in silicone fluid and V is the drug molecular volume. The relative merits of SNZ and ONZ over MNZ (the current reference treatment) are discussed. The data support development of vaginal rings for sustained release of 5-nitroimidazole compounds for treatment of BV.

Online survey of consumer awareness and perceptions of a Massachusetts law for 12-month supply of contraception

ObjectivesThis study aimed to characterize awareness of a 2017 Massachusetts (MA) law that ensures access to a 12-month supply of short-acting contraceptive methods (e.g., pill, patch, and vaginal ring) among short-acting contraceptive users in MA and to identify perceived benefits and concerns of a 12-month supply. Study designAn online survey was administered to a Qualtrics panel of MA women who were using short-acting contraceptive methods and were insured by an eligible health plan. The survey’s primary outcome was general awareness of the law; interest in, receipt of, and perceived benefits and risks of a 12-month supply were also elicited. Analysis included descriptive statistics and bivariate and multivariable analyses examining factors associated with awareness of the law. ResultsAmong the 207 survey respondents, 76% were aware of the law, and 93% expressed interest in receiving a 12-month supply of a short-acting method; however, only 9% received it. Respondents identified as White (66%), privately insured (59%), and pill users (44%). Concerns about a 12-month supply included privacy, product expiration, and change in personal medical status. Perceived benefits included avoiding multiple trips to pharmacy and increased compliance. Multivariable analyses showed general awareness of the law was only associated with employer-based insurance, with those respondents having 75% lower odds of being aware of the law than respondents with Medicaid coverage. ConclusionAlthough a high percentage of women surveyed were aware of the law and most were interested in receiving a 12-month supply of their short-acting method, the low percentage who have received a 12-month supply suggests barriers to policy uptake. ImplicationsThis study describes perceptions of the 12-month supply provision of the contraception Act Advancing Contraceptive Coverage and Economic Security in our State law. Addressing consumer concerns may be important to improve the implementation and dissemination of this state policy change.

Next generation 3D-printed intravaginal ring for prevention of HIV and unintended pregnancy

Globally, there are 20 million adolescent girls and young women living with HIV who have limited access to long-acting, effective, women-controlled preventative methods. Additionally, although there are many contraceptive methods available, globally, half of all pregnancies remain unintended. Here we report the first 3D-printed multipurpose prevention technology (MPT) intravaginal ring (IVR) for HIV prevention and contraception. We utilized continuous liquid interface production (CLIP™) to fabricate MPT IVRs in a biocompatible silicone-based resin. Etonogestrel (ENG), ethinyl estradiol (EE), and islatravir (ISL) were loaded into the silicone poly(urethane) IVR in a controlled single step drug loading process driven by absorption. ENG/EE/ISL IVR promoted sustained release of drugs for 150 days in vitro and 14 days in sheep. There were no adverse MPT IVR-related findings of cervicovaginal toxicity or changes in vaginal biopsies or microbiome community profiles evaluated in sheep. Furthermore, ISL IVR in macaques promoted sustained release for 28 days with ISL-triphosphate levels above the established pharmacokinetic benchmark of 50–100 fmol/106 PBMCs. The ISL IVR was found to be safe and well tolerated in the macaques with no observed mucosal cytokine changes or alterations in peripheral CD4 T-cell populations. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls.

National medical eligibility criteria for contraceptive use 2023: focus on women's reproductive health: A review

Reproductive health care involves helping families in this area with the provision of the necessary information. This is recognized as a key step in improving the health of men, women and children and is a fundamental human right. Everyone has the right to have access to a correct understanding of reproductive health care, choice of contraceptive method and the opportunity to benefit from scientific progress in this area. Over the past 35 years, significant progress has been made in the development of new contraceptives: the content of hormones in combined oral contraceptives has significantly decreased, inert intrauterine contraceptives have been replaced by more progressive, levonorgestrel-containing ones including low-dose generation. Combined hormonal compounds were synthesized in the form of injections, patches and vaginal rings, progestogen implantable and injectable contraceptives. Women who use contraceptives must take into account the state of health (including the presence of endocrine pathology) in order to use them without harm to their health. Based on the World Health Organization Medical Eligibility Criteria for Contraceptive Methods 2015, the Russian Medical Eligibility Criteria for Contraceptive Methods 2023 is designed to become an important tool in daily practice of doctors.

Foreign bodies inside us - Trends and knowledge regarding long-acting reversible contraceptives (LARCs) use, factors influencing of contraceptives choice-making process, and the dual-method use among Polish college-aged women

Introduction: The choice-making process of the contraceptive method seems complex and influenced by many factors. Long-acting reversible contraceptives require mechanical interference with the woman's body. For some, it will be an insurmountable barrier whilst for others a chance to enjoy a successful sex life without fear of pregnancy. Recognizing the factors influencing their use will allow us to identify target groups, increase awareness, and spread knowledge about them.&#x0D; Purpose: This study aimed to assess contraceptive use trends and knowledge, focusing on long-acting reversible contraceptives (LARCs) and vaginal rings, also to identify predictors associated with their use and analyze the decision-making process for dual-method use (hormonal plus barrier method) among female college students in Poland.&#x0D; Materials and methods: A self-administered questionnaire including 44 questions in the form of a web-based survey distributed among peers in social media platforms and forums.&#x0D; Results: In the survey a total of 700 female students aged 19±25 took part. All the questions about LARC and vaginal rings were answered correctly by only 19 participants (2.71%). The most knowledgeable were medical students (p&lt;0.0001). Out of 55 LARC and vaginal ring users (7.86%), 47 female students (76.4%,) stated the improvement of their life. Of the methods interfering with the body, the study group most frequently chose the vaginal ring (38.1%) and least frequently the hormone injection (0.1%). &#x0D; Conclusions: Participants’ knowledge of LARC methods and vaginal rings is insufficient and its main influencing factors are faculty type and frequency of intercourse. LARC and vaginal disc are not the first contraception choice. Fear of pregnancy is the most common factor for dual method use.

Hormonal contraception use and insomnia: A nested case-control study

Evidence is limited concerning possible associations between the use of hormonal contraception and insomnia. We applied the nested case-control design on a nationwide sample of women, aged 15–49 years, derived from national health care registries to characterize the association between the use of hormonal contraception and the occurrence of insomnia. There were altogether 294,356 users and 294,356 non-users of hormonal contraception. 11,105 new cases of insomnia emerged among the 1,148,969 person-years of the follow-up period of two years. All the significant associations of hormonal contraception with insomnia emerged among the participants aged 34 years or younger, and if only the tertiary care data was concerned, among the those aged 15–19 years. The users of the fixed combination of drospirenone and ethinylestradiol as well as that of cyproterone and ethinylestradiol had significantly decreased odds for insomnia, whereas the users levonorgestrel-releasing intrauterine devise as well as those of vaginal ring with etonogestrel and ethinylestradiol had significantly increased odds for insomnia as compared with non-users. Our findings suggest that different products prescribed for hormonal contraception may be differentially associated with the occurrence of insomnia.

The impact of combined contraceptive vaginal ring on vaginal environment: an observational, longitudinal study

Purpose To assess the relationship between combined contraceptive vaginal ring (CVR) and vaginal microbiome using 16S rRNA gene sequencing. Materials and methods We enrolled 20 women for 8 weeks in an open-label study using CVR (NuvaRing®) that delivered 15 mcg ethinylestradiol and 120 mcg etonogestrel daily. The vaginal microbiome was assessed at baseline and after 2 months by sequencing the 16S rRNA genes amplified from the total genomic DNA isolated from the sample. Results Bacterial distribution richness and equity did not significantly change after 2 months, and the dominant bacterial strain was Lactobacillus crispatus. Only one woman with a history of vestibulodynia and recurrent vulvovaginitis showed an increase in bacterial biodiversity, with a switch to the relative abundance of anaerobic bacteria. Conclusions Our results suggest that CVR does not adversely affect the composition and structure of the vaginal microbiome. However, special care should be taken in patients with a history of vestibulodynia and/or recurrent vulvovaginal infections.

Adolescent Girls and Young Women's Experiences with Disclosing Oral PrEP or Dapivirine Vaginal Ring Use: a Multi-Country Qualitative Analysis.

Effective use of oral pre-exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in Eastern and Southern Africa, partly due to stigma and opposition from key influencers. Understanding AGYW's experiences of disclosure of different PrEP modalities to key influencers may inform strategies to motivate uptake and adherence. We analyzed qualitative in-depth interviews and focus group discussions data from 119 participants in the MTN-034/REACH (Reversing the Epidemic in Africa with Choices in HIV Prevention) study of oral PrEP and the dapivirine vaginal ring (ring) to explore AGYW's disclosure experiences. We found that AGYW disclosure experiences varied across influencers and product type. The ring was disclosed less often to most influencers, except partners, because it was discreet. Oral PrEP was disclosed more often, because pills were more common and to avoid HIV stigma given that oral PrEP resembled HIV treatment. Ultimately, disclosure typically led most key influencers to support product use through reminders and encouragement. While disclosure yielded positive support from influencers, further community awareness of both PrEP products is essential to reduce potential opposition and perceived stigma.Clinical Trial Number: NCT03593655.

(017) Systemic Estradiol Menopause Management: Return to the Old-Fashioned Way

Abstract Introduction The mean systemic estradiol value in menopausal women is &amp;lt; 10 pg/ml, consistent with ovarian failure. Such low values are associated with multiple symptoms including hot flashes, night sweats, insomnia, mood changes and irritability, cognitive changes, weight gain and slowed metabolism. Contemporary management with systemic estradiol, maximizing safety and efficacy, emphasizes non-oral, non-injection estradiol replacement therapies including systemic daily gels, twice weekly or weekly patches or three-month vaginal rings. Most women (&amp;gt;60%) who try these systemic therapies in our sexual medicine clinic have been successful at reducing bothersome symptoms. We have identified a subset of women who cannot achieve sufficient symptom relief despite using contemporary estradiol strategies due to lack of efficacy, negative side effects, (rings cannot stay in the vagina or values are too high initially and then too low, patches cause rashes or fall off, gels are too messy) or financial concerns. For these patients, we have advised a return to the “old-fashioned way” using weekly intramuscular (IM) injection of either estradiol valerate or cypionate. Estradiol cypionate was first described as well as introduced for medical use in 1952. Objectives This study examines the experiences of this subset of women in one practice using weekly injections of estradiol valerate or cypionate for either efficacy or financial reasons. Methods This chart review identified a subset of 16 patients (mean age 59 +/− 8 years) at a single site who had been prescribed estradiol valerate or cypionate when symptoms of genitourinary syndrome of menopause (GSM) persisted despite use of estradiol replacement gels, patches or rings, or cost was prohibitive. We have advised weekly IM injection of either estradiol valerate (20 mg/ml; starting dose 0.05 ml or 1 mg) or estradiol cypionate (5 mg/ml; starting dose 0.2 ml or 1 mg). We compared relief of bothersome symptoms from earlier estradiol treatments to current IM injection and compared monthly costs of each treatment based on GoodRx prices, assuming medications were not covered by insurance. Results All patients using weekly injections of estradiol valerate or cypionate had their estradiol-based GSM symptoms ameliorated without complaint of inconvenience or discomfort using injections. The risks of IM injections of estradiol are similar to those of topical administration, requiring concomitant progesterone use in women with a uterus. Concerning finances, using a GoodRx coupon, a 5 ml bottle of estradiol valerate costs approximately $50 and should last at least one year, reducing monthly cost to approximately $5/month. A 5 ml bottle of estradiol cypionate costs approximately $150 and should last at least 6 months, thus about $25/month. In contrast, generic patches are approximately $40/month, gels $150/month and the ring $170/month. While there remains an abhorrence for injections, the motivation for systemic estradiol replacement superseded any inconvenience of using an injectable medication and the 27-gauge ½ inch needle is associated with minimal pain. No significant side effects were noted with IM injection. Conclusions For certain individuals, sometimes the “old-fashioned way” works better both in terms of efficacy and cost, providing relief of bothersome menopausal symptoms. Disclosure No.

Baseline preferences for oral pre-exposure prophylaxis (PrEP) or dapivirine intravaginal ring for HIV prevention among adolescent girls and young women in South Africa, Uganda and Zimbabwe (MTN-034/IPM-045 study).

Adolescent girls and young women (AGYW) in sub-Saharan Africa are disproportionately affected by the HIV epidemic and face an array of challenges using proven behavioral and biomedical prevention methods. To address the urgent need for expanding prevention options, we evaluated the baseline preferences of HIV prevention methods among participants enrolled in the MTN-034/REACH crossover trial along with their stated product preference prior to product initiation. AGYW aged 16-21 years were enrolled at 4 study sites: Cape Town and Johannesburg, South Africa; Kampala, Uganda; and Harare, Zimbabwe and randomly assigned to the sequence of using oral PrEP and the dapivirine ring for 6 months each, followed by a choice period in which they could choose either product (or neither) for an additional six months. Eligible AGYW were HIV-negative, not pregnant and using effective contraception for at least two months prior to enrollment. Descriptive statistics were used to summarize demographic and behavioral data while multinomial analysis was used to determine predictors of stated product preference (ring or oral PrEP). Of the 247 AGYW enrolled in REACH, 34% were aged 16-17 and 89% had a primary partner.The median age of sexual debut was 16 years and 40% had ever been pregnant. At screening, 35% of participants were diagnosed with a sexually transmitted infection (STI), 39% had an AUDIT-C score associated with harmful drinking and 11% reported intimate partner violence in the past 6 months. Overall, 28% of participants, had CESD-10 scores suggestive of depressive symptoms (≥12) in the past week. At baseline, similar proportions stated a preference for the ring and oral PrEP (38.1% and 40.5% respectively), with 19% of participants stating they preferred both products equally. Only study site was significantly associated with product preference (P<0.05) with AGYW from Johannesburg having higher odds of preferring the ring and those from Kampala having higher odds of preferring both options equally. We successfully enrolled African AGYW with a clear unmet need for HIV prevention. The balanced preference between the two products suggests that multiple biomedical prevention options may be appealing to this age group and could address their prevention needs.

The Future of Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: A Global Qualitative Consultation on Provider Perspectives on New Products and Differentiated Service Delivery

Differentiated service delivery and new products, such as long-acting injectable cabotegravir (CAB-LA) and the dapivirine vaginal ring (DVR), could increase uptake and use of pre-exposure prophylaxis (PrEP) for HIV prevention. We explored PrEP provider perspectives on differentiated PrEP service delivery and new PrEP products to inform World Health Organization (WHO) guidelines and programme implementation. 150 PrEP providers who participated in a WHO survey were randomly selected and 67 were invited for interviews based on geographic representation, provider cadre, gender, experience with community-based PrEP service delivery, and familiarity with new PrEP products. Semi-structured interviews were conducted virtually. Key themes were inductively extracted relating to differentiated service delivery and benefits and concerns regarding new PrEP products. 30 PrEP providers from 24 countries were interviewed. Across regions, providers were supportive of differentiated service delivery to respond to clients’ needs and preferences, maintain services during COVID-19, and ensure access for priority populations that may face access challenges. Providers welcomed prospects of offering CAB-LA to their clients but had concerns about HIV testing, costs, and the need for clinic-based services, including staff who can administer injections. Providers felt the DVR was potentially important for some cisgender women, especially young clients and female sex workers, and raised fewer concerns compared to injectable PrEP. Providers’ views are critical for the development of guidelines and implementing programmes that will best serve PrEP users. Understanding areas where provider capacities and biases may create barriers can define opportunities for training and support to ensure that providers can deliver effective programmes.

O-044 The future of contraception

Abstract In 1960, the first hormonal contraceptive agent, Enovid approved by the Food and Drug Administration in the United States. The pill contained mestranol 150 mcg and norethynodrel 10 mg. High dose pills containing &amp;gt;50 mcg of estrogen were discontinued in 1988 due to a higher risk of myocardial infraction and stroke secondary to thrombosis. Until recently, the only estrogens used in combination OCPs were mestranol and ethinyl estradiol (EE). Estetrol (E4) and 17-beta estradiol have been added to newer pill and intravaginal ring (IVR) formulations in order to reduce the risk of thrombosis. Progestins confer the primary contraceptive effect in combination agents and can be used without estrogens. First generation progestins include norethynodrel, ethynodiol diacetate, norethindrone and norethindrone acetate (estranes). Second generation progestins include norgestrel and levonorgestrel (gonanes). Third generation include gestoden, desogrestrel and norgestimate, which are less androgen versions of the second generation progestins. Fourth generation progestins have no androgenicity include drospirenone. The fourth generation progestin is a 17 carbon compound which separates it from the other progestins that are primarily 19 carbon derivatives of androgens. Segesterone acetate (SA) is a newer progestin that is less potent and has no androgenic properties. SA, combined with EE, is currently being used in an IVR. However, clinical trials are ongoing using SA with 17-beta estradiol in an IVR and another with EE as a contraceptive gel. Other new methods of hormonal contraception include progestins in a biodegradable implant, longer acting injectables that can last 6-12 months, transdermal patches that are imbedded with an array of microneedles where either the contraceptive agent is in a reservoir or in the needles themselves. Microchip technology is being developed by the Gates Foundation that would allow levonorgestrel to be released systemically at will over a 16-year period using a remote device. Multipurpose technologies are being developed utilizing contraceptive pills, injectables and IVRs containing hormonal agents as well as medications to prevent STI/HIV acquisition.

A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women.

Primary objectives were to evaluate the safety and systemic pharmacokinetics (PK) of DARE-HRT1, an intravaginal ring (IVR), which releases 17β2-Estradiol (E2) with progesterone (P4) for 28 days in healthy postmenopausal women. This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women with an intact uterus. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d). They used the IVR for three 28-day cycles, inserting a new IVR monthly. Safety was measured by treatment emergent adverse events and changes in systemic laboratories and the endometrial bilayer width. Baseline adjusted plasma PK of E2, P4, and estrone (E1) was described. Both DARE-HRT1 IVR were safe. All treatment emergent adverse events were mild or moderate and were distributed similarly among IVR1 versus IVR2 users. Month 3 median maximum plasma (Cmax) P4 concentrations were 2.81 and 3.51 ng/mL and Cmax E2 was 42.95 and 77.27 pg/mL for IVR1 and IVR2 groups, respectively. Month 3 median steady state (Css) plasma P4 concentrations were 1.19 and 1.89 ng/mL, and Css E2 was 20.73 and 38.16 pg/mL for IVR1 and IVR2 users, respectively. Both DARE-HRT1 IVRs were safe and released E2 in systemic concentrations, which were in the low, normal premenopausal range. Systemic P4 concentrations predict endometrial protection. Data from this study support further development of DARE-HRT1 for the treatment of menopausal symptoms.

Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya.

Globally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies. Healthy women ages 18-34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition. Among 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36-90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded >2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was <10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and -27.1% to -20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased >50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively). TFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR. NCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382].