Vaginal Ring Research Articles

The effect of non-oral hormonal contraceptives on hypertension and blood pressure: A systematic review and meta-analysis.

Oral contraceptives (OC) are associated with increased risk of hypertension and elevated blood pressure (BP). Whether non‐oral hormonal contraceptives have similar associations is unknown. We sought to investigate the effect of non‐oral hormonal contraceptive (NOHC) use on the risk of hypertension and changes in BP, compared to non‐hormonal contraceptive and OC use. We searched bibliographic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) until August 2020. Studies reporting risk of hypertension or changes in systolic and diastolic BP with NOHC use compared with either non‐hormonal contraceptive or OC use. screening, full‐text review, data extraction, and quality assessment were completed in duplicate. For studies reporting dichotomous outcomes, we reported results as relative risk with 95% confidence intervals (CI). A random‐effects model was used to estimate pooled weighted mean difference and 95% CI of change in BP. Twenty‐five studies were included. A lower incidence of hypertension was observed with injectable contraceptive use compared to non‐hormonal contraceptive and OC use, although it was unclear if this was statistically significant. Compared to non‐hormonal contraceptive use, injectable contraceptive use was associated with increased BP (SBP: 3.24 mmHg, 95%CI 2.49 to 3.98 mmHg; DBP: 3.15 mmHg, 95%CI 0.09 to 6.20 mmHg), the hormonal intra‐uterine device use was associated with reduced BP (SBP: −4.50 mmHg, 95%CI −8.44 to −0.57 mmHg; DBP: −7.48 mmHg, 95% −14.90 to −0.05 mmHg), and the vaginal ring was associated with reduced diastolic BP (−3.90 mmHg, 95%CI −6.67 to −1.13 mmHg). Compared to OC use, the injectable contraceptive use was associated with increased diastolic BP (2.38 mmHg, 95%CI 0.39 to 4.38 mmHg). NOHC use is associated with changes in BP which differ by type and route of administration. Given the strong association between incremental increases in BP and cardiovascular risk, prospective studies are required.

Non-oral routes, novel formulations and devices of contraceptives: An update.

Family planning enables society to prevent unintended pregnancies and helps in attaining desired spacing between the pregnancies. It is done with the use of contraceptive methods and infertility treatments. The use of contraceptives serves to ease maternal ill-health and reduce pregnancy-related deaths and helps to decrease the number of unsafe abortions and HIV transmission from mothers to newborns. The most popular contraception method is a daily dose of combined oral contraceptives pills. However, poor compliance and various adverse effects are common problems of oral contraceptives that considerably reduce their long-term use. Thus, several non-oral contraceptive options have been developed for better compliance, reduced side effects and improved therapeutic efficacy. This review presented the non-oral contraceptive formulations given by different routes such as transdermal, nasal, subcutaneous, intramuscular, intrauterine and vaginal routes. These formulations delivering contraceptives, mainly through devices, include transdermal patches and microneedles, nasal sprays, intrauterine devices and intrauterine systems, vaginal rings, contraceptive implants and contraceptive injections, which are unique in their specific advantages and drawbacks.

Oral pre-exposure prophylaxis preference, uptake, adherence and continuation among adolescent girls and young women in Kampala, Uganda: a prospective cohort study.

IntroductionOral pre‐exposure prophylaxis (PrEP) has been scaled up; however, data from real‐world settings are limited. We studied oral PrEP preference, uptake, adherence and continuation among adolescent girls and young women (AGYW) vulnerable to HIV in sub‐Saharan Africa.MethodsWe conducted a prospective cohort study among 14‐ to 24‐year‐old AGYW without HIV who were followed for 12 months in Kampala, Uganda. Within at least 14 days of enrolment, they received two education sessions, including demonstrations on five biomedical interventions that are; available (oral PrEP), will be available soon (long‐acting injectable PrEP and anti‐retroviral vaginal ring) and in development (PrEP implant and HIV vaccine). Information included mode and frequency of delivery, potential side effects and method availability. Volunteers ranked interventions, 1 = most preferred to 5 = least preferred. Oral PrEP was “preferred” if ranked among the top two choices. All were offered oral PrEP, and determinants of uptake assessed using Poisson regression with robust error variance. Adherence was assessed using plasma tenofovir levels and self‐reports.ResultsBetween January and October 2019, 532 volunteers were screened; 285 enrolled of whom 265 received two education sessions. Mean age was 20 years (SD±2.2), 92.8% reported paid sex, 20.4% reported ≥10 sexual partners in the past 3 months, 38.5% used hormonal contraceptives, 26.9% had chlamydia, gonorrhoea and/or active syphilis. Of 265 volunteers, 47.6% preferred oral PrEP. Willingness to take PrEP was 90.2%; however, uptake was 30.6% (n = 81). Following enrolment, 51.9% started PrEP on day 14 (same day PrEP offered), 20.9% within 30 days and 27.2% after 30 days. PrEP uptake was associated with more sexual partners in the past 3 months: 2–9 partners (aRR = 2.36, 95% CI: 1.20–4.63) and ≥10 partners (aRR 4.70, 95% CI 2.41–9.17); oral PrEP preference (aRR 1.53, 95% CI 1.08–2.19) and being separated (aRR 1.55, 95% CI 1.04–2.33). Of 100 samples from 49 volunteers during follow up, 19 had quantifiable tenofovir levels (>10 μg/L) of which only three were protective (>40 μg/L).ConclusionsHalf of AGYW preferred oral PrEP, uptake and adherence were low, uptake was associated with sexual behavioural risk and oral PrEP preference. Development of alternative biomedical products should be expedited to meet end‐user preferences and, community delivery promoted during restricted movement.

The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause: A Randomized-Controlled Trial.

The postmenopausal urinary bladder microbiome is not well defined. The aims of this study were to characterize the effect of vaginal estrogen on the vaginal and urinary bladder microbiome in postmenopausal women and describe any clinical associations with the symptoms of genitourinary syndrome of menopause. This was a participant-masked, randomized controlled trial comparing the effect of a 12-week course of an estrogen-containing vaginal ring to a placebo vaginal ring. Standardized evaluations were performed at baseline and 12 weeks. Vaginal samples were obtained for pH, vaginal maturation index, and microbiome analysis. Concomitant catheterized urine samples were obtained for microbiome analysis. 16S ribosomal RNA gene sequencing was performed to characterize the resident microbial communities, with Lactobacillus relative abundance as the primary outcome variable. Genitourinary syndrome of menopause symptoms was measured using validated questionnaires (Pelvic Floor Distress Inventory-Short Form, Female Sexual Function Index, Vulvovaginal Symptoms Questionnaire). Of the 39 postmenopausal women randomized, baseline characteristics were similar between arms, with a mean age of 62 years and mean vaginal pH of 5.0. Using intention-to-treat analysis, there were no significant changes in vaginal or urinary Lactobacillus relative abundance. Two participants in each arm removed their ring prior to the end of the study. Eighty percent of participants experienced at least 1 bothersome genitourinary syndrome of menopause symptom. Vulvovaginal dryness and urinary frequency were most common at baseline, whereas painful intercourse and urinary urgency were most common at the final visit, none of which were statistically significant. Our study did not show a significant change in the bacterial composition of the vaginal or urinary bladder microbiome after either vaginal ring in this relatively asymptomatic postmenopausal population.

Evaluating the effectiveness of NSAIDs and vasopressin receptor antagonists as primary dysmenorrhea treatments

Primary dysmenorrhea describes the intensely painful uterine contractions experienced during menstruation. It is associated with elevated prostaglandin production in the uterine area and primarily affects adolescents. There are several treatment options available for primary dysmenorrhea, however, there is a lapse in research assessing their efficacy and reliability. The purpose of this review is to provide an overview and evaluation of two forms of treatment for primary dysmenorrhea: non-steroidal antiinflammatory drugs (NSAIDs) and vasopressin receptor antagonists. While studies conducted on the effectiveness of NSAIDs have shown consistent results, research conducted on vasopressin receptor antagonists remains contradictory. As such, the clinical efficacy of vasopressin receptor antagonists remains inconclusive, exposing several limitations and areas that require additional research. Furthermore, this review discusses the efficacy of promising novel treatments (i.e. levonorgestrel-releasing intrauterine devices, intravaginal rings, transdermal patches) and highlights the importance of additional studies for validation.

In Vitro Investigation and Characterization of Silicone Matrix IVR Loaded with Levonorgestrel: A Propper Method for Hormon Replacement Therapy

Introduction: Among 3 to 30 percent of women of reproductive age, experience abnormal uterine bleeding (AUB). Vaginal rings are one of the systems of interest for the local delivery of hormones that due to their polymeric structure allow prolonged release of drug. In this study, the design and fabrication of matrix vaginal rings containing levonorgestrel (LNG) were investigated.
 Methods: In this experimental study, at first, two pieces of aluminum mold were designed, then base (A) and cross-linker parts (B) of polymer with LNG were mixed and 48 polymeric rings containing LNG were manufactured by injection molding method. To achieve the desired drug release values in a given time, the effect of temperature, rpm, release environment, different initial loading, cross-linker percentage and a mathematical model to predict release and swelling test were investigated.
 Results: As a result of the experiments, it was revealed that with increasing drug loading, the release rate rises, while increasing the cross-linker percentage reduced the drug release. Finally, the ring A:B=100:9.5 with an initial loading of 0.2 % LNG relative to silicon was selected as an appropriate ring, and release experiments were performed at 37 °C, shaker speed of 80 rpm, and release medium containing 10 % ethanol. Drug release values were measured by spectrophotometer and analyzed by SPSS statistical software version 16.
 Conclusion: Based on the results, it can be deduced that matrix vaginal ring containing LNG is a suitable drug delivery system for prolonged release of LNG for treatment of AUB that depending on the drug initial loading and cross-linker percentage, the required diffusion coefficient, and release rate can be achieved in a certain time.

Long-acting injections for HIV prevention among women in sub-Saharan Africa

Women in sub-Saharan Africa are one of the groups at highest risk of HIV in the world, encompassing 38% of new cases globally.1 Multiple HIV prevention modalities have been developed and trialled in women in sub-Saharan Africa with limited success. Tenofovir vaginal gels showed initial promise with a 39% overall reduction in HIV infection,2 but later trials showed no evidence of protection.3 Two clinical trials of dapivirine vaginal rings showed an overall 27–31% risk reduction.4,5 Daily oral pills containing tenofovir disoproxil fumarate are currently the standard for pre-exposure prophylaxis (PrEP).

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

ABSTRACT Introduction Low systemic estradiol values (<10 pg/ml) experienced by menopausal women are associated with multiple symptoms including hot flashes, night sweats, insomnia, mood changes/irritability, vaginal dryness, dyspareunia, dysuria, low libido, reduced arousal/orgasm, cognitive changes, weight gain and slowed metabolism. Intramuscular estradiol cypionate was first described for medical use in 1952 to treat symptoms of menopausal ovarian failure. Systemic management has evolved, including daily gels, weekly/twice weekly patches and three-month vaginal rings. These therapies have successfully reduced bothersome symptoms in >60% women presenting to our clinic. A subset of women cannot achieve sufficient symptom relief using these strategies due to lack of efficacy, negative side effects, (rings cannot stay in the vagina; 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 returning to the “old-fashioned way” using weekly or twice weekly intramuscular (IM) injection of either estradiol valerate or cypionate. Objective This study examines experiences of this subset of women in our practice using injections of estradiol valerate or cypionate for either enhancing efficacy or financial reasons. Methods This chart review identified 22 patients (mean age 61 +/- 8 years) who had been prescribed estradiol valerate or cypionate when symptoms of genitourinary syndrome of menopause (GSM) persisted despite use of estradiol replacement gels/patches/rings, or cost was prohibitive. We have advised weekly/twice weekly IM injection of either estradiol valerate (20 mg/ml; starting dose 0.05 ml (1 mg) weekly or 0.025 ml (0.5 mg) twice weekly) or estradiol cypionate (5 mg/ml; starting dose 0.2 ml weekly (1 mg) or 0.1 ml (0.5 mg twice weekly), utlizing 1 ml syringes with 27-gauge ½ inch needle. Injections were administered into the vastus lateralis on the antero-lateral surface at mid-thigh. Alcohol was used to prepare the skin, and compression was applied for 2 minutes after the injection. We compared relief of bothersome symptoms from earlier estradiol treatments to current IM injection and monthly costs of each treatment based on GoodRx prices, assuming medications were not covered by insurance. Results All patients using injections of estradiol valerate or cypionate had their estradiol-based GSM symptoms ameliorated without complaint of inconvenience or discomfort using injections. All described injection pain as minimal. No significant side effects were noted with IM injection. 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 lasting at least a year costs approximately $50, reducing monthly cost to approximately $5/month. A 5 ml bottle of estradiol cypionate lasting at least 6 months costs approximately $150, thus about $25/month. In contrast, generic patches can cost approximately $40/month, gels $150/month and the ring $170/month. Conclusions While there remains an aversion to injections in some patients, the motivation for IM systemic estradiol replacement superseded any inconvenience. For certain individuals, the “old-fashioned way” works better both in terms of efficacy and cost, providing relief of bothersome GSM symptoms. Disclosure No

Correlates of non-persistent endocrine disrupting chemical mixtures among reproductive-aged Black women in Detroit, Michigan

Some studies indicate that Black women have higher exposure to multiple non-persistent endocrine disrupting chemicals (EDCs) than white women, but little is known about correlates of exposure to EDC mixtures. Using baseline data from a prospective cohort study of reproductive-aged Black women (N = 751), we characterized profiles of EDC mixtures and identified correlates of exposure. At baseline, we quantified biomarkers of 16 phthalates, 7 phenols, 4 parabens, and triclocarban in urine and collected covariate data through self-administered questionnaires and interviews. We used principal component (PC) analysis and k-means clustering to describe EDC mixture profiles. Associations between correlates and PCs were estimated as the mean difference (β) in PC scores, while associations between correlates and cluster membership were estimated as the odds ratio (OR) of cluster membership. Personal care product use was consistently associated with profiles of higher biomarker concentrations of non-persistent EDCs. Use of nail polish, menstrual and vaginal products (e.g., vaginal powder, vaginal deodorant), and sunscreen was associated with a mixture of phthalate and some phenol biomarkers using both methods. Current vaginal ring use, a form of hormonal contraception placed inside the vagina, was strongly associated with higher concentrations of high molecular weight phthalate biomarkers (k-means clustering: OR = 2.42, 95% CI = 1.28, 4.59; PCA: β = −0.32, 95% CI = −0.71, 0.07). Several dietary, reproductive, and demographic correlates were also associated with mixtures of EDC biomarkers. These findings suggest that personal care product use, diet, and contraceptive use may be sources of exposure to multiple non-persistent EDCs among reproductive-aged Black women. Targeted interventions to reduce exposure to multiple EDCs among Black women are warranted.

Color, Scent and Size: Exploring Women's Preferences Around Design Characteristics of Drug-Releasing Vaginal Rings

Steroid-releasing vaginal rings are available for contraception and estrogen replacement therapy, and a new antiretroviral-releasing ring was recently approved for HIV prevention. Marketed rings are white or transparent in appearance, non-scented, and supplied as one-size-fits-all devices with diameters ranging from 54 to 56 mm. In this study, drug-free silicone elastomer rings were manufactured in different sizes, colors and scents, and the opinions/preferences of 16 women (eThekwini District, South Africa; 20–34 years) assessed through focus group discussions and thematic analysis. Opinions varied on ring color and scent, with some women preferring specific colors or scent intensities, while for others these attributes were unimportant. Concerns about color and scent were linked to perceptions around vaginal health and safety related to chemical composition. There was greater agreement on preferred ring size; flexibility and width were considered important factors for insertion and comfort. Greater choice with ring products could facilitate acceptability and overall uptake.

Comparison of the Vaginal and Urinary Effects of Pesser Use and Local Estrogen Use with Pessary in Postmenopausal Women with Pelvic Organ Prolapse

Aim: To investigate and compare the vaginal and urinary effects of the use of a vaginal pessary ring and vaginal local oestrogen together with pessary prescribed for postmenopausal women with pelvic organ prolapse (POP) who did not wish to have a POP operation. 
 Method: This prospective case-control study was conducted in the Gynaecology and Obstetrics Clinics of Turhal State Hospital and Tokat State Hospital between May 2021 and July 2021. Two groups were formed of 25 patients given a vaginal pessary ring for treatment, and 25 who were given vaginal local oestrogen together with the pessary ring. Comparisons were made between the groups in respect of age, gravida, parity, pelvic pain, vaginal itching-discharge-dryness-bleeding, findings of urinary incontinence, the presence of bacteria in the urine, and white blood cells (WBC) and c reavtive protein (CRP) values. 
 Results: In the comparisons of women using pessary alone and those using local oestrogen together with the pessary, the complaints of pelvic pain (p=0.034) and vaginal dryness (p=0.037) were determined at a higher rate in the group that used the pessary alone. 
 Conclusion: The reason for the higher rate of pelvic pain and vaginal dryness seen in the women using pessary alone is that without oestrogen the pessary has the effect of a foreign body on the vaginal mucosa, thereby increasing vaginal inflammation. However, local oestrogen increased the complaint of unnecessary vaginal bleeding in some patients. Taking all these findings in to consideration, the use of pessary and local oestrogen should be applied carefully in POP treatment.

Contraceptive Vaginal Ring: Nuvaring

For more than four decades ago, researchers began developing Vaginal contraceptive rings characterized by two guiding principles: the ability vaginal epithelium is made up of a layer of cells that line within the structure vaginal canal ingest the application of steroid ability of elastomers to release hormones at a virtually constant rate. Only two kinds of contraceptive vaginal rings (CVRs) it has been completed to market: NuvaRing, a combination ring that distributes etonogestrel (ENG) and ethinyl estradiol (EE), and Progering, a progesterone-releasing ring for nursing women. The main benefits CVRs are a type of efficacy (tablets are comparable to or slightly superior to), simple to use (no need to remember aa regular schedule), user control over initiation and removal, release rate that is practically constant allowing for flexibility low dosage, greater bioavailability, and excellent cycle control because of the integrated ring. CVRs can produce cervical bleeding and complaints, band expulsion is typical, the ring can During coitus, in addition vaginal implantation can be painful for certain women. CVRs are completely safe, efficacious, Women find it quite appealing, in conformity with studies discussed in this work. CVRs are without a doubt a novel, very efficient contraception for women, expanding their hormonal contraception options.

Systems Analysis Reveals Contraceptive-Induced Alteration of Cervicovaginal Gene Expression in a Randomized Trial.

Hormonal contraceptives (HCs) are vital in managing the reproductive health of women. However, HC usage has been linked to perturbations in cervicovaginal immunity and increased risk of sexually transmitted infections. Here, we evaluated the impact of three HCs on the cervicovaginal environment using high-throughput transcriptomics. From 2015 to 2017, 130 adolescent females aged 15–19 years were enrolled into a substudy of UChoose, a single-site, open-label randomized, crossover trial (NCT02404038) and randomized to injectable norethisterone–enanthate (Net-En), combined oral contraceptives (COC), or etonorgesterol/ethinyl–estradiol–combined contraceptive vaginal ring (CCVR). Cervicovaginal samples were collected after 16 weeks of randomized HC use and analyzed by RNA-Seq, 16S rRNA gene sequencing, and Luminex analysis. Participants in the CCVR arm had a significant elevation of transcriptional networks driven by IL-6, IL-1, and NFKB, and lower expression of genes supporting epithelial barrier integrity. An integrated multivariate analysis demonstrated that networks of microbial dysbiosis and inflammation best discriminated the CCVR arm from the other contraceptive groups, while genes involved in epithelial cell differentiation were predictive of the Net-En and COC arms. Collectively, these data from a randomized trial represent the most comprehensive “omics” analyses of the cervicovaginal response to HCs and provide important mechanistic guidelines for the provision of HCs in sub-Saharan Africa.

Where are the pregnant and breastfeeding women in new pre-exposure prophylaxis trials? The imperative to overcome the evidence gap

Pregnant and breastfeeding populations are at substantial risk of acquiring HIV in some settings, yet are underrepresented in clinical trials of new pre-exposure prophylaxis (PrEP) agents. Several PrEP formulations are in development (eg, vaginal rings, long-acting injectables, and other modalities). Pregnant and breastfeeding populations are typically excluded from initial clinical trials. We identified 14 PrEP trials of novel agents in non-pregnant or non-breastfeeding populations, and six phase 1-3 trials and open label extensions among pregnant and breastfeeding populations, that are currently ongoing or complete. A framework shift is needed to consider the ethical costs of excluding pregnant and breastfeeding populations at risk for HIV in PrEP clinical trials and promote inclusion to maximise the benefits from PrEP tools in the pipeline. Research on new PrEP agents should include pregnant and breastfeeding populations to avoid delays in reaching those who could benefit from PrEP after efficacy is established.

Acceptability of the Dapivirine Vaginal Ring in Postmenopausal US Women

For women in the United States who remain sexually active beyond child-bearing years, susceptibility to HIV infection remains, yet condom use is low. We assessed acceptability of the dapivirine vaginal ring (ring) among 96 postmenopausal US women enrolled in a placebo-controlled multisite phase II trial of the ring, using questionnaires and in-depth interviews. Three quarters of women reported “perfect” adherence (ring never out) over the 3-month trial period. At study exit, the ring was found to be very easy to use by 72%, very comfortable to wear by 65%, and 4% reported it ever interfered with their daily activities. The most common worries among participants at preinitiation had decreased significantly at study exit (e.g., worries about inserting the ring declined from 46% to 6%, discomfort during daily activities from 53% to 3%, ring not staying in place from 48% to 14%, all p < 0.0001). Despite some couples feeling the ring during sex, the ring was perceived as more suitable than condoms for prevention because it was not burdensome to use, did not interfere with erection, and provided (for some) additional vaginal lubrication. The ring is a promising, highly acceptable HIV prevention method that is suitable to the lives of postmenopausal women and their male partners and can provide them with an additional prevention choice.Clinical Trials Registration: NCT02010593.

Impact of Group Prenatal Care on Contraceptive Use at Twelve Weeks Postpartum.

To compare the prevalence of highly effective contraceptive use by 12weeks postpartum among participants of Centering Pregnancy®, a model of group prenatal care (GPC), and traditional prenatal care (TPC), and to investigate differences in contraceptive method choice by type of prenatal care. We performed a retrospective review of all eligible patients who participated in GPC (n = 143) and a random sample of patients participating in TPC (n = 290) who followed up at our institution within 12weeks of delivery. Our primary outcome was the proportion of participants using a highly effective contraceptive method within 12weeks postpartum. Contraceptives were classified in tiers (Tier 1, long-acting reversible and permanent contraception; Tier 2, oral contraceptive pills, transdermal patch, vaginal ring, or injection; Tier 3, barrier and fertility awareness methods, withdrawal, spermicide; and no method). Tier 1 and Tier 2 methods were considered highly effective. The prevalence of highly effective contraceptive use by 12weeks postpartum was 63.6% (91 of 143) and 63.1% (183 of 290) among participants in GPC and TPC, respectively (p = 0.99). We found no difference in Tier 1 versus other method use (adjusted odds ratio (aOR) 1.05, 95% CI 0.95-1.15, p = 0.34) or Tier 2 versus other method use between groups (aOR 0.98, 95% CI 0.89-1.08, p = 0.69), in a multivariable model controlling for demographic and clinical factors. The prevalence of highly effective contraceptive use at 12weeks postpartum was not different between GPC and TPC participants in this study. GPC was not associated with increased use of Tier 1 or Tier 2 contraceptive methods.

Fused deposition modeling three-dimensional printing of flexible polyurethane intravaginal rings with controlled tunable release profiles for multiple active drugs

We designed and engineered novel intravaginal ring (IVR) medical devices via fused deposition modeling (FDM) three-dimensional (3D) printing for controlled delivery of hydroxychloroquine, IgG, gp120 fragment (encompassing the CD4 binding site), and coumarin 6 PLGA-PEG nanoparticles (C6NP). The hydrophilic polyurethanes were utilized to 3D-print reservoir-type IVRs containing a tunable release controlling membrane (RCM) with varying thickness and adaptable micro porous structures (by altering the printing patterns and interior fill densities) for controlled sustained drug delivery over 14 days. FDM 3D printing of IVRs were optimized and implemented using a lab-developed Cartesian 3D printer. The structures were investigated by scanning electron microscopy (SEM) imaging and in vitro release was performed using 5 mL of daily-replenished vaginal fluid simulant (pH 4.2). The release kinetics of the IVR segments were tunable with various RCM (outer diameter to inner diameter ratio ranging from 1.12 to 2.61) produced from FDM 3D printing by controlling the printing perimeter to provide daily zero-order release of HCQ ranging from 23.54 ± 3.54 to 261.09 ± 32.49 µg/mL/day. IgG, gp120 fragment, and C6NP release rates demonstrated pattern and in-fill density-dependent characteristics. The current study demonstrated the utility of FDM 3D printing to rapidly fabricate complex micro-structures for tunable and sustained delivery of a variety of compounds including HCQ, IgG, gp120 fragment, and C6NP from IVRs in a controlled manner.Graphical abstract

Twelve-month supply of short-acting contraception methods: Pharmacists’ perspectives on implementation of new state law

BackgroundOral contraceptives and other short-acting reversible contraceptive (SARC) methods such as the patch, vaginal ring, and medroxyprogesterone injections are used by approximately 30% of people using contraception. People may face barriers in obtaining a timely and adequate supply of their SARCs. It is well established that dispensing more than 1-month supply at a time is more convenient for patients, improves continuation, and decreases the risk of unintended pregnancy. Given the potential for public health impact, 20 states, including Massachusetts, have expanded access to a 12-month supply of SARCs. ObjectivesThe goal of this qualitative study was to explore Massachusetts pharmacists’ general awareness and specific knowledge of the state’s 2017 Act Advancing Contraceptive Coverage and Economic Security in Our State (ACCESS) law, explore barriers to the implementation of the law, and elicit recommendations to improve uptake of this practice. MethodsSemistructured interviews were conducted with a purposeful sample of community pharmacists in Massachusetts between September 2020 and May 2021 using a pretested interview guide. Interviews were audio recorded and professionally transcribed. Data collection ceased when theoretical saturation was achieved. Data were analyzed using modified grounded theory, including code book development and line-by-line and axial coding. ResultsSixteen pharmacists from diverse practice settings participated in the interviews. All the pharmacists (100%) reported that they had received no training on the ACCESS law, and only 1 pharmacist reported having complete knowledge of the specifics of the law. We identified key themes and subthemes related to pharmacists’ concerns about implementation of the law at the system, pharmacy, and patient level, including insurance coverage, communication of new laws, stocking, supply, and misuse by patients. ConclusionAddressing the need for pharmacist training and communication regarding new regulations may improve provision of an extended supply of SARC methods.

Comparison of contraceptive sales before and during the COVID-19 pandemic in Brazil

Objective The aim of the study was to assess the impact of the COVID-19 pandemic on sales of modern contraceptive methods in Brazil. Methods Monthly sales data were analysed of short-acting reversible contraceptive methods and long-acting reversible contraceptive (LARC) methods (implants and intrauterine contraception) and COVID-19 related deaths. Contraceptive methods were grouped as follows: emergency contraception (EC); oral contraception, vaginal rings and transdermal patches; injectable contraception; LARC methods including the copper intrauterine device (Cu-IUD); and LARC methods excluding the Cu-IUD. Results Contraceptive sales showed a non-significant increase in 2020 compared with the previous year; average sales ranged from 12.8 to 13.0 million units per month. Sales of injectable contraceptives increased between March and June 2020 and EC pills between June and July 2020; the variation in sales of pills, patches and rings was not significant. Sales of the levonorgestrel-releasing intrauterine system (LNG-IUS) and the etonogestrel (ENG) implant showed three patterns: a decrease in sales between February and May 2020 (coinciding with the closure of family planning services), an increase in sales after May 2020 (coinciding with the first COVID-19-related deaths), and a further increase in sales after July 2020 (corresponding to the increasing number of deaths from COVID-19). Conclusion The COVID-19 pandemic has disrupted the Brazilian health care system. Since many family planning clinics were closed, sales of most modern contraceptives fell during 2020; however, the increase in sales of the LNG-IUS and ENG implant in the private sector indicates inequitable access to modern contraceptive methods.

Promise, perils and cautious optimism: the next frontier in long-acting modalities for the treatment and prevention of HIV.

Purpose of reviewThis paper provides a critical review of recent therapeutic advances in long-acting (LA) modalities for human immunodeficiency virus (HIV) treatment and prevention.Recent findingsLA injectable antiretroviral therapy (ART) has been approved in the United States, Canada and Europe; the United States also has approved LA injectable preexposure prophylaxis (PrEP) and the World Health Organization has recommended the vaginal PrEP ring. Current LA PrEP modalities in clinical trials include injections, films, rings, and implants; LA ART modalities in trials include subcutaneous injections and long-term oral pills. Although LA modalities hold incredible promise, global availability is inhibited by long-standing multilevel perils including declining multilateral funding, patent protections and lack of political will. Once available, access and uptake are limited by factors such as insurance coverage, clinic access, labor markets, stigma, and structural racism and sexism. These must be addressed to facilitate equitable access for all.SummaryThere have been tremendous recent advances in the efficacy of LA ART and PrEP modalities, providing renewed hope that ‘ending the HIV epidemic’ is within reach. However, pervasive socio-structural inequities limit the promise of LA modalities, highlighting the need for cautious optimism in light of the embedded inequities in the trajectory of research, development, and population-level implementation.