Division of Gynecology
Washington University School of Medicine
Dr. Madden studies the effects of different forms of oral contraception and intrauterine devices on the development of bacterial vaginosis. Dr. Madden followed her BIRCWH training by succesfully transitioning into an independent K23 award. She has been extremely productive, publishing more than 30 papers detailing her observational studies, randomized clinical trials, and decision-making and implementation science. She also serves as the Principal Investigator on a Patient-Centered Outcomes Research Initiative (PCORI) Research Award for a project implementing patient-centered contraceptive provision into community settings. She is as an Associate Professor in the Department of Obstetrics and Gynecology at Washington University.
BIRCWH Scholar from 07/01/2009 until 03/31/2012
Bacterial Vaginosis-Associated Bacteria in Women Using Oral and Intrauterine Contraception
The goal of this BIRCWH Program application is to provide a period of focused mentored research to assist in the transition from junior faculty to an independent and successful investigator in the area of women’s reproductive infectious disease. We propose an innovative research project using molecular diagnostic methods to investigate the effect of contraception on rates of bacterial vaginosis.
Normal vaginal microflora is essential for the protection of the vaginal tract from colonization by organisms that cause diseases such as vaginitis and sexually transmitted infections. Bacterial vaginosis results from a shift away from the normal lactobacillus dominated flora of the vagina and is the most common cause of symptomatic vaginal discharge among reproductive-aged women. It is associated with a number of adverse outcomes, including an increased risk of sexually transmitted infection acquisition, pelvic inflammatory disease, preterm labor, and post-surgical infection. The etiology of bacterial vaginosis is complex and remains poorly understood. Limited diagnostic tools are currently available. Therefore, the diagnosis is most commonly made using clinical criteria, which do not provide information about the pathogenic vaginal bacterial species present.
Contraceptive use is widely prevalent in the United States with more than 40% of women reporting visits for contraceptive care annually. Currently less than 2% of women use intrauterine contraception, however this percentage is increasing. Previous studies have reported elevated rates of bacterial vaginosis in women who use intrauterine contraception and decreased rates in women who use combined oral contraception; however, it is not clear if the type of contraception causes a real change in the vaginal microflora. As intrauterine contraceptive use increases in the United States, study of the relationship between bacterial vaginosis and contraception is highly warranted. Further understanding of the possible consequences of contraceptive choice may help avoid the adverse reproductive health sequelae associated with bacterial vaginosis.
Here, we propose to use species-specific16S recombinant RNA (rRNA) polymerase chain reaction (PCR) assays to investigate the association between the presence of 3 bacterial vaginosis-associated bacterial species (BVAB1, BVAB2 and BVAB3), and combined oral versus intrauterine contraception. We will also investigate the correlation between the presence of BVAB1, BVAB2, and/or BVAB3 and the presence and concentration of three bacterial vaginosis-associated amines with the symptoms and clinical diagnosis of bacterial vaginosis.
Our primary hypothesis is that women using intrauterine contraception (IUC) will be more likely to have abnormal vaginal microflora, as measured by the presence of BVAB1, BVAB2, or BVAB3, than women using combined oral contraceptives (COC). Furthermore, we will determine if there is a difference in the incidence of bacterial vaginosis-associated bacteria between users of copper (Cu-IUC) and levonorgestrel (LNG-IUC) intrauterine contraceptives
1.Compare the incidence of bacterial vaginosis (BV) between users of COC, Cu-IUC, and LNG-IUC. We will monitor women enrolled in our study over the course of 12 months for clinical symptoms of BV and the presence of BVAB1, BVAB2, and BVAB3 using bacterium-specific 16S rRNA PCR assays to test the hypothesis that the use of IUC, particularly Cu-IUC, is associated with the development of BV.
2.Determine the correlation of clinical symptoms and diagnosis of BV and quantitative measures of the presence of bacterial vaginosis-associated bacteria and metabolic markers of anaerobic bacteria. We will test for: 1) the presence of BVAB1, BVAB2, and BVAB3 by 16S rRNA PCR, and 2) elevated concentrations of putrescine, cadaverine, and tyramine by gas chromatography and mass spectrometry (GC/MS), in women with intermediate vaginal flora or BV by Nugent score to determine the association of these diagnostic tests with the clinical symptoms of BV.
The completion of these two aims will: 1) determine if a true association exists between contraception and bacterial vaginosis, and 2) improve the available diagnostic tools for BV, thereby better informing the diagnosis and treatment of BV.