COVID-19 Testing in African American Churches Using a Faith-Health- Academic Partnership.

Increasing access to COVID-19 testing in influential, accessible community settings is needed to address COVID-19 disparities among African Americans. We describe COVID-19 testing intervention approaches conducted in Kansas City, Missouri, African American churches via a faith-health-academic partnership. Trained faith leaders promoted COVID-19 testing with church and community members by implementing multilevel interventions using a tailored toolkit and standard education information. The local health department conducted more than 300 COVID-19 tests during or after Sunday church services and outreach ministry activities. (Am J Public Health. 2022;112(S9):S887-S891. https://doi.org/10.2105/AJPH.2022.306981).

The Role of Labor Induction in Racial Disparities in Cesarean Delivery.

We examined the interaction between race and labor induction in cesarean delivery in a cohort of 600,000 deliveries in the Cerner Health Facts database. Black women had higher likelihood cesarean (28.9 vs. 26.5%) and lower likelihood of induction of labor at delivery compared to white women (27.2 vs. 32.5%). Induction modified the association between race and cesarean-Black women (odds ratio=1.36, 95% confidence interval 1.30, 1.43) who were induced had significantly increased odds of cesarean delivery.

Associations between the vaginal microbiome and Candida colonization in women of reproductive age.

BACKGROUND: The composition of bacteria within the vaginal microbiome has garnered a lot of recent attention and has been associated with reproductive health and disease. Despite the common occurrence of yeast (primarily Candida) within the vaginal microbiome, there is still an incomplete picture of relationships between yeast and bacteria (especially lactobacilli), as well as how such associations are governed. Such relationships could be important to a more holistic understanding of the vaginal microbiome and its connection to reproductive health. OBJECTIVE: The objective of the study was to perform molecular characterization of clinical specimens to define associations between vaginal bacteria (especially Lactobacillus species) and Candida colonization. In vitro studies were conducted to test the 2 most common dominant Lactobacillus species (Lactobacillus crispatus and Lactobacillus iners) in their ability to inhibit Candida growth and to examine the basis for such inhibition. STUDY DESIGN: A nested cross-sectional study of reproductive-age women from the Contraceptive CHOICE Project was conducted. Vaginal swabs from 299 women were selected to balance race and bacterial vaginosis status, resulting in a similar representation of black and white women in each of the 3 Nugent score categories (normal [0-3], intermediate [4-6], and bacterial vaginosis [7-10]). Sequencing of the 16S ribosomal gene (V4 region) was used to determine the dominant Lactobacillus species present (primarily Lactobacillus iners and Lactobacillus crispatus), defined as >50% of the community. Subjects without dominance by a single Lactobacillus species were classified as Diverse. A Candida-specific quantitative polymerase chain reaction targeting the internally transcribed spacer 1 was validated using vaginal samples collected from a second cohort of women and used to assess Candida colonization. Two hundred fifty-five nonpregnant women with sufficient bacterial biomass for analysis were included in the final analysis. Generalized linear models were used to evaluate associations between Lactobacillus dominance, sociodemographic and risk characteristics, and vaginal Candida colonization. In separate in vitro studies, the potential of cell-free supernatants from Lactobacillus crispatus and Lactobacillus iners cultures to inhibit Candida growth was evaluated. RESULTS: Forty-two women (16%) were vaginally colonized with Candida. Microbiomes characterized as Diverse (38%), Lactobacillus iners-dominant (39%), and Lactobacillus crispatus-dominant (20%) were the most common. The microbiome, race, and Candida colonization co-varied with a higher prevalence of Candida among black women and Lactobacillus iners-dominant communities compared with white women and Lactobacillus crispatus-dominant communities. Lactobacillus iners-dominant communities were more likely to harbor Candida than Lactobacillus crispatus-dominant communities (odds ratio, 2.85, 95% confidence interval, 1.03-7.21; Fisher exact test, P = .048). In vitro, Lactobacillus crispatus produced greater concentrations of lactic acid and exhibited significantly more pH-dependent growth inhibition of Candida albicans, suggesting a potential mechanism for the clinical observations. CONCLUSION: In nonpregnant women, Lactobacillus iners-dominant communities were significantly more likely to harbor Candida than Lactobacillus crispatus-dominant communities, suggesting that Lactobacillus species have different relationships with Candida. In vitro experiments indicate that Lactobacillus crispatus may impede Candida colonization more effectively than Lactobacillus iners through a greater production of lactic acid.

Menstruation and contraception patterns of female adolescent transplant recipients.

BACKGROUND: There is a lack of knowledge regarding menstrual cycles and contraception usage for adolescent transplant patients and families. Solid organ transplant patients start teratogenic medications which have pregnancy implications. We explore adolescent female solid organ transplant recipient and guardian's contraceptive knowledge and attitudes as well as menstrual patterns. METHODS: A cross-sectional descriptive research design was utilized to collect information from adolescent female transplant patients who are on mycophenolate mofetil after solid organ transplant and their guardians within our freestanding children's hospital via a survey. The sample consisted of all female adolescent patients who have completed a solid organ transplant and are on mycophenolate mofetil from April 2016 through May 2017. RESULTS: Twenty-one patients were approached, of which nineteen patients and seventeen guardians completed the survey. The average age of the patient was 16.2 years. The average age at time of transplant was 12.2 years. The type of transplants includes renal (57.1%), heart (23.8%), and liver (4.8%). There were six patients (33.3%) who had a history of sexual activity; among these patients, the mean number of partners in the last year was 1.2. Menstrual concerns included dysmenorrhea, irregular bleeding, and heavy bleeding pre- and post-transplant, respectively. Participants reported contraceptive counseling prior to and after transplant approximately half of the time. CONCLUSIONS: Adolescent solid organ transplant patients have multiple reproductive needs including contraception, dysmenorrhea, and irregular bleeding. Integration of contraceptive knowledge into clinical care received by adolescents with solid organ transplants is supported by knowledge gained through this study.

Association between obesity and bacterial vaginosis as assessed by Nugent score.

BACKGROUND: Bacterial vaginosis is 1 of the most common vaginal conditions in the United States. Recent studies have suggested that obese women have an abnormal microbiota reminiscent of bacterial vaginosis; however, few studies have investigated the prevalence of bacterial vaginosis in overweight and obese populations. Moreover, despite the increased prevalence of obesity and bacterial vaginosis in black women, it is not known whether racial disparities exist in the relationship between obesity and bacterial vaginosis. OBJECTIVE: The objective of this study was to examine the relationship between body mass index and bacterial vaginosis as determined by Nugent score and to determine the influence of race in this context. STUDY DESIGN: We performed a cross-sectional study using patient data and vaginal smears from 5918 participants of the Contraceptive CHOICE Project. Gram-stained vaginal smears were scored with the Nugent method and categorized as bacterial vaginosis-negative (Nugent score, 0-3), bacterial vaginosis-intermediate (Nugent score, 4-6), or bacterial vaginosis-positive (Nugent score, 7-10). Body mass index was determined with Centers for Disease Control and Prevention guidelines, and obese individuals were categorized as class I, II, or III obese based on National Institutes of Health and World Health Organization body mass index parameters. Linear regression was used to model mean differences in Nugent scores; Poisson regression with robust error variance was used to model prevalence of bacterial vaginosis. RESULTS: In our cohort, 50.7% of participants were black; 41.5% were white, and 5.1% were of Hispanic ethnicity; the average age of 25.3 years old. Overall, 28.1% of participants were bacterial vaginosis-positive. Bacterial vaginosis was prevalent in 21.3% of lean, 30.4% of overweight, and 34.5% of obese women (P<.001). The distribution of bacterial vaginosis-intermediate individuals was similar across all body mass index categories. Compared with the scores of lean women, Nugent scores were highest among overweight and obese class I women (adjusted mean difference: overweight women, 0.33 [95% confidence interval, 0.14-0.51] and obese women, 0.51 [95% confidence interval, 0.29-0.72]). Consistent with this, overweight and obese women had a higher frequency of bacterial vaginosis compared with lean women, even after adjustment for variables that included race. Among white women, the prevalence of bacterial vaginosis was higher for overweight and class I and class II/III obese white women compared with lean white women, which is a phenomenon not observed among black women and suggests an effect modification. CONCLUSION: Overweight and obese women have higher Nugent scores and a greater occurrence of bacterial vaginosis compared with lean women. Black women have a greater prevalence of bacterial vaginosis independent of their body mass index compared with white women.

Genetic variation associated with preterm birth in African-American women.

BACKGROUND: Preterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery. OBJECTIVE: The objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women. STUDY DESIGN: This is a secondary analysis of a randomized trial that evaluated periodontal disease and preterm birth. Women were enrolled between 6 and 20 weeks' gestation at 3 prenatal care clinics between 2004 and 2007. Maternal DNA samples were collected and analyzed using a custom 1536 single-nucleotide polymorphismgenotyping array designed to assess genes involved in inflammation. Women were included in this study if they self-identified as African American. We excluded women with a multiple gestation or an indicated preterm delivery. We performed allele- and genotype-based analyses to evaluate the association between spontaneous preterm birth and tag single-nucleotide polymorphisms. We used a logistic regression to adjust for prior preterm birth in our genotype-based analysis. In a subgroup analysis, we compared women who delivered at <34 weeks' gestation to women who delivered at term. Within the microarray, we identified ancestry informative markers and compared global ancestry estimates among women who delivered preterm with those who delivered at term. RESULTS: Of the 833 African-American women in the study with genotype data, 77 women (9.2%) had a spontaneous preterm birth, whereas 756 women delivered at term. In an allele-based analysis, 4 single-nucleotide polymorphisms related to the genes for protein kinase C-α (PRKCA) were associated with increased risk of spontaneous preterm birth <37 weeks, whereas a single single-nucleotide polymorphism related to fms-related tyrosine kinase 1 (FLT1) was associated with spontaneous preterm birth <34 weeks. A genotype-based analysis revealed similar associations between single-nucleotide polymorphisms related to the PRKCA genes and spontaneous premature delivery. Additionally, single-nucleotide polymorphisms related to matrix metalloproteinase-2 (MMP2), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and interleukin 16 (IL16) genes were associated with spontaneous preterm birth <37 weeks in genotype-based analysis. Genetic variants related to MMP2, matrix metalloproteinase-1 (MMP1), and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) genes were associated with higher rates of preterm birth <34 weeks. Ancestry estimates were similar between the women who had a spontaneous preterm birth and those who delivered at term. CONCLUSION: We identified tag single-nucleotide polymorphisms related to 7 genes that are critical to inflammation, extracellular remodeling, and cell signaling that were associated with spontaneous preterm birth in African-American women. Specifically, we found a strong association with the PRKCA gene. Genetic variation in these regions of the genome may be important in the pathogenesis of preterm birth. Our results should be considered in the design of future genomic studies in prematurity.

Invited commentary: recruiting for epidemiologic studies using social media.

Social media-based recruitment for epidemiologic studies has the potential to expand the demographic and geographic reach of investigators and identify potential participants more cost-effectively than traditional approaches. In fact, social media are particularly appealing for their ability to engage traditionally "hard-to-reach" populations, including young adults and low-income populations. Despite their great promise as a tool for epidemiologists, social media-based recruitment approaches do not currently compare favorably with gold-standard probability-based sampling approaches. Sparse data on the demographic characteristics of social media users, patterns of social media use, and appropriate sampling frames limit our ability to implement probability-based sampling strategies. In a well-conducted study, Harris et al. (Am J Epidemiol. 2015;181(10):737-746) examined the cost-effectiveness of social media-based recruitment (advertisements and promotion) in the Contraceptive Use, Pregnancy Intention, and Decisions (CUPID) Study, a cohort study of 3,799 young adult Australian women, and the approximate representativeness of the CUPID cohort. Implications for social media-based recruitment strategies for cohort assembly, data accuracy, implementation, and human subjects concerns are discussed.

Effectiveness of long-acting reversible contraception.

BACKGROUND: The rate of unintended pregnancy in the United States is much higher than in other developed nations. Approximately half of unintended pregnancies are due to contraceptive failure, largely owing to inconsistent or incorrect use. METHODS: We designed a large prospective cohort study to promote the use of long-acting reversible contraceptive methods as a means of reducing unintended pregnancies in our region. Participants were provided with reversible contraception of their choice at no cost. We compared the rate of failure of long-acting reversible contraception (intrauterine devices [IUDs] and implants) with other commonly prescribed contraceptive methods (oral contraceptive pills, transdermal patch, contraceptive vaginal ring, and depot medroxyprogesterone acetate [DMPA] injection) in the overall cohort and in groups stratified according to age (less than 21 years of age vs. 21 years or older). RESULTS: Among the 7486 participants included in this analysis, we identified 334 unintended pregnancies. The contraceptive failure rate among participants using pills, patch, or ring was 4.55 per 100 participant-years, as compared with 0.27 among participants using long-acting reversible contraception (hazard ratio after adjustment for age, educational level, and history with respect to unintended pregnancy, 21.8; 95% confidence interval, 13.7 to 34.9). Among participants who used pills, patch, or ring, those who were less than 21 years of age had a risk of unintended pregnancy that was almost twice as high as the risk among older participants. Rates of unintended pregnancy were similarly low among participants using DMPA injection and those using an IUD or implant, regardless of age. CONCLUSIONS: The effectiveness of long-acting reversible contraception is superior to that of contraceptive pills, patch, or ring and is not altered in adolescents and young women. (Funded by the Susan Thompson Buffet Foundation.).

Fertility after intrauterine device removal: a pilot study.

BACKGROUND: Despite high efficacy, only 7.7% of women in the United States currently using contraception use an IUD. There is little published contemporary data about fertility rates after IUD use, especially in nulliparous women and women using the hormonal IUD. STUDY DESIGN: We recruited sexually active women 18 to 35 years of age enrolled in the Contraceptive CHOICE Project who had discontinued a contraceptive method and desired pregnancy. RESULTS: In this pilot project, we enrolled 69 former IUD users (19 copper and 50 levonorgestrel) and 42 former non-IUD users. Pregnancy rates at 12 months were similar between the two groups; 81% of IUD users became pregnant compared to 70% of non-IUD users (p = 0.18). In the Cox model, there was no difference in the time to pregnancy in IUD users compared to non-IUD users (HRadj 1.19, 95% CI 0.74-1.92). African American race was the only variable associated with reduced fertility (HRadj 0.40, 95% CI 0.24-0.67). CONCLUSIONS: We found no difference in 12-month pregnancy rates or time to pregnancy between former IUD users and users of other contraceptive methods. However, there was a clinically and statistically significant reduction in fertility in African American women.

Hydrolysis of secreted sialoglycoprotein immunoglobulin A (IgA) in ex vivo and biochemical models of bacterial vaginosis.

Bacterial vaginosis (BV) is a common polymicrobial imbalance of the vaginal flora associated with a wide variety of obstetric and gynecologic complications including serious infections and preterm birth. As evidenced by high recurrence rates following treatment, interventions for BV are still lacking. Several hydrolytic activities, including glycosidases and proteases, have been previously correlated with BV and have been hypothesized to degrade host sialoglycoproteins that participate in mucosal immune functions. Sialidase activity is most predictive of BV status and correlates strongly with adverse health outcomes. Here we combine clinical specimens with biochemical approaches to investigate secretory immunoglobulin A (SIgA) as a substrate of BV-associated glycosidases and proteases. We show that BV clinical specimens hydrolyze sialic acid from SIgA, but not in the presence of the sialidase inhibitor dehydro-deoxy-sialic acid. The collective action of BV-associated glycosidases exposes underlying mannose residues of SIgA, most apparent on the heavily N-glycosylated secretory component of the antibody. Terminal sialic acid residues on SIgA protect underlying carbohydrate residues from exposure and hydrolysis by exoglycosidases (galactosidase and hexosaminidase). It is known that both IgG and SIgA are present in the human reproductive tract. We show that the IgG heavy chain is more susceptible to proteolysis than its IgA counterpart. Gentle partial deglycosylation of the SIgA secretory component enhanced susceptibility to proteolysis. Together, these data support a model of BV in which SIgA is subject to stepwise exodeglycosylation and enhanced proteolysis, likely compromising the ability of the reproductive mucosa to neutralize and eliminate pathogens.

Sexually transmitted infection prevalence in a population seeking no-cost contraception.

BACKGROUND: We used universal screening to determine the prevalence rates of Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV) in 9256 women enrolling into a contraceptive study. METHODS: We offered screening using nucleic acid amplification or culture to all participants enrolling into the Contraceptive CHOICE Project. Demographic characteristics were collected through staff-administered questionnaires. Univariate and multivariable analyses were performed to assess the risk of sexually transmitted infection at baseline and to compare risk profiles of CT and TV. RESULTS: Results were available for 8347 consenting women with satisfactory results; 656 (7.9%) were tested positive for 1 or more infections. Approximately one third of participants were older than 26 years, and half were identified as African American. There were 35 cases of GC for a prevalence of 0.4% (95% confidence interval [CI], 0.3-0.6), 260 cases of CT for a prevalence of 3.1% (95% CI, 2.8-3.5), and 410 cases of TV for a prevalence of 4.9% (95% CI, 4.4-5.4). Black women were more likely to be tested positive (odds ratio, 3.95; 95% CI, 3.08-5.06) compared with white women and accounted for 81.3% of cases. T. vaginalis was more prevalent in black women (8.9%) compared with white women (0.9%). Older age was a risk factor for TV, whereas younger age was associated with CT. Of the 656 positive cases, 106 (16%) were diagnosed in women older than 25 years, falling outside traditional screening guidelines. CONCLUSION: We found GC, CT, and TV to be more prevalent than current national statistics, with TV being the most prevalent. Current screening recommendations would have missed 16% of infected women.

The impact of emotional, physical, and sexual abuse on contraceptive method selection and discontinuation.

OBJECTIVES: We evaluated the impact of exposure to emotional, physical, or sexual abuse on contraceptive method selection and discontinuation. METHODS: We performed a secondary analysis of 7170 women enrolled in the Contraceptive CHOICE Project in St. Louis, Missouri, a prospective cohort study in which 9256 women were provided their preferred method of contraception at no cost from 2007 to 2011. We defined contraceptive discontinuation as device removal or nonuse for at least 4 weeks within the first 12 months after initiation. RESULTS: One third of women experienced some abuse in their lifetimes. Women with an abuse history were as likely as those without to select a long-acting reversible contraceptive method and more likely to choose a contraceptive injection, the patch, or the ring. When we compared women who were abused to those who were not, rates of discontinuation at 12 months were higher among women who selected long-acting reversible contraception (17% vs 14%; P = .04) and significantly higher among women who selected non-long-acting methods (56% vs 47%; P < .001). Type of abuse did not alter the association between abuse and contraceptive continuation. CONCLUSIONS: Previous experiences of abuse are associated with both contraceptive method selection and continuation.

Correlates of HIV-Related Stigmas Among African American Church-Affiliated Populations in Kansas City.

HIV-related stigmas contribute to disparities, and contact with HIV-positive individuals has been suggested to reduce stigma. Faith-based organizations have been recognized as important to stigma reduction efforts among African American populations; however, relatively few church-based studies have measured HIV-related stigma. This study uses baseline data (N = 1,448) from a study with 14 African American churches in Kansas City, Missouri and Kansas, to examine correlates of HIV-related stigmas among church members and community members accessing church social services using two previously validated scales that measure discomfort interacting with individuals with HIV and anticipated stigma or rejection. Knowing someone with HIV was associated with lower discomfort, even after adjusting for sociodemographic characteristics and sexual risk, HIV knowledge, previous communication about HIV at church, and mean drug and homosexuality stigmas. Knowing someone with HIV was not associated with anticipated stigma or rejection after adjustment. Contact-based interventions hold promise for reducing discomfort around people with HIV among church-affiliated populations.

Resident microbes shape the vaginal epithelial glycan landscape.

Epithelial cells are covered in carbohydrates (glycans). This glycan coat or "glycocalyx" interfaces directly with microbes, providing a protective barrier against potential pathogens. Bacterial vaginosis (BV) is a condition associated with adverse health outcomes in which bacteria reside in direct proximity to the vaginal epithelium. Some of these bacteria, including Gardnerella, produce glycosyl hydrolase enzymes. However, glycans of the human vaginal epithelial surface have not been studied in detail. Here, we elucidate key characteristics of the "normal" vaginal epithelial glycan landscape and analyze the impact of resident microbes on the surface glycocalyx. In human BV, glycocalyx staining was visibly diminished in electron micrographs compared to controls. Biochemical and mass spectrometric analysis showed that, compared to normal vaginal epithelial cells, BV cells were depleted of sialylated N- and O-glycans, with underlying galactose residues exposed on the surface. Treatment of primary epithelial cells from BV-negative women with recombinant Gardnerella sialidases generated BV-like glycan phenotypes. Exposure of cultured VK2 vaginal epithelial cells to recombinant Gardnerella sialidase led to desialylation of glycans and induction of pathways regulating cell death, differentiation, and inflammatory responses. These data provide evidence that vaginal epithelial cells exhibit an altered glycan landscape in BV and suggest that BV-associated glycosidic enzymes may lead to changes in epithelial gene transcription that promote cell turnover and regulate responses toward the resident microbiome.

Risk of bacterial vaginosis in users of the intrauterine device: a longitudinal study.

BACKGROUND: Users of the intrauterine device (IUD) may be at increased risk for bacterial vaginosis (BV). Our objective was to compare the incidence of BV in women using the IUD with women using combined oral contraceptives (COC), the contraceptive vaginal ring, and the contraceptive patch. METHODS: We prospectively recruited women negative for BV at baseline. Monthly, for 6 months, participants returned a self-obtained vaginal smear for Gram stain by mail. BV was diagnosed by a Nugent score ≥7. We performed Cox proportional hazards regression to investigate associations between demographic and behavioral characteristics, contraceptive method, and incident BV. RESULTS: We enrolled 153 women negative for BV at baseline; 90 (59%) women who chose the IUD and 63 (41%) who chose COC, ring, or patch. There were 35 women with BV at one or more time points. The incidence of BV was 37.0% among IUD users and 19.3% in COC, ring, and patch users (P = 0.03). In the univariate analysis, race, IUD use, intermediate flora, and irregular vaginal bleeding were significantly associated with BV. In the adjusted model, IUD users were no more likely to acquire BV (hazards ratio [HRadj]: 1.28, 95% confidence interval [CI]: 0.53-3.06) than COC, ring, and patch users. The associations between intermediate flora and irregular bleeding and BV remained significant (HRadj: 3.30, 95% CI: 1.51-7.21, and HRadj: 2.54, 95% CI: 1.03-6.24, respectively). CONCLUSIONS: The association between IUD use and BV appears to be mediated by irregular vaginal bleeding. Intermediate flora is associated with an increased incidence of BV.

Predictors of male partner treatment for sexually transmitted infection.

BACKGROUND: Patient-initiated notification is a commonly used practice for notifying sex partners of possible exposure to a sexually transmitted infection (STI); however, 46% to 75% of partners are never treated. The Contraceptive CHOICE Project (CHOICE) is a longitudinal cohort study of women that provides no-cost contraception, STI testing, treatment to participants, and free partner treatment. Our objective was to evaluate characteristics of women who tested positive for chlamydia, gonorrhea, or trichomoniasis, and their association with successful partner treatment. METHODS: We analyzed baseline survey and STI testing, notification, and treatment data from the first 5087 participants enrolled in CHOICE. We considered "treated partners" to be men who received antibiotic treatment at the study clinic or by a prescription through the study. Independent predictors of successful partner treatment were identified using univariate analysis and multivariable analysis using Poisson regression with robust error variance. RESULTS: Forty-four percent of male partners were successfully treated. Women whose partners were less likely to obtain treatment were black (adjusted Relative Risk (RR adj) RR adj = 0.6; 95% confidence interval [CI]: 0.5-0.8) or reported some concern about future STI with the partner (RR adj = 0.6; 95% CI: 0.4, 0.8). Women whose partners were more likely to receive treatment were living with their partner (RR adj = 1.4; 95% CI: 1.1-1.8) or reported recent inconsistent condom use (RR adj = 1.5; 95% CI: 1.1-2.1). CONCLUSIONS: The male partner treatment rate resulting from female patient-initiated partner notification in our study was low. Our findings highlight the need to develop novel notification interventions that yield higher partner treatment rates and consider patient-specific factors, such as race and relationship status.

Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial.

OBJECTIVE: The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system. STUDY DESIGN: We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. RESULTS: There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34). CONCLUSION: The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo.