Grant: Operating Grant

Over 150 million women worldwide take hormonal contraceptives and millions more are on various hormonal therapies for reproductive disorders. Clinical and experimental studies provide clear evidence that female reproductive hormones affect susceptibility and immune responses to sexually transmitted infections (STI), including Chlamydia, gonorrhoea, HSV-2 and HIV-1. Despite such widespread use and strong evidence of connection to STIs, the mechanism of hormone regulation of susceptibility is unknown. Even more worrisome is the fact that areas of high progesterone based contraceptives, which have the strongest link to increased susceptibility, overlap with high HIV incidence making this a major public health issue. Our work in this area over past few years has shown that estradiol protects against sexually transmitted infections while progesterone increases inflammation. On the other hand, Depo-provera, a progesterone-based contraceptive increases susceptibility to sexually transmitted viruses. In this application we propose to comprehensively understand how female sex hormones affect susceptibility and immune responses and then use this information to suggest alternative hormonal contraceptives that are safe for use by all women.