Regulation of cervical mucus secretion
Awarded 2015
Complex Family Planning Fellowship Research
Leo Han, MD
Oregon Health and Science University

Hormonal contraception remains the primary form of contraception used by US women. Progestin-based hormonal methods are thought to cause thickening of the cervical mucus that causes poor sperm penetration. While it is widely accepted that progesterone is a mediator of mucus changes observed at midcycle, the regulation of this effect is not well understood. Subsequently, lingering questions regarding the onset and extent of progestins actions on cervical mucus affects our prescribing practice of current progestin-based contraception.
Current studies of progestin-only contraception deal with challenges to isolate hormone driven effects. Mucus evaluation of a progestin must be timed to coincide with the peak effect of endogenous estradiol and potential trough effect of the contraceptive steroid. Additionally, ovulation presents an important confounder as there is also endogenous progesterone being produced, subsequently suppressing endogenous estradiol production. As there is a convolution of forces on mucus from both estradiol withdrawal and endogenous progesterone, the early and late effects of progesterone signaling remain incompletely understood.
Our study seeks to evaluate the changes in human cervical mucus in response to progestogens as an initial step toward clarifying these relationships. Our hypothesis is that direct effects of progesterone on the endocervix, independent of estrogen withdrawal, cause contraceptive changes to cervical mucus. We plan to conduct a randomized, prospective, crossover study examining cervical mucus changes in a small cohort of women in whom we will suppress circulating hormonal levels by administering a GnRH agonist. We will then artificially replace estradiol and progesterone in order to differentiate their effects on mucus. We will be looking closely at the immediate changes in mucus when .35 mg of norethindrone is administered in this experimental setting. We will also collect cervical cell samples and determine whether genes for membrane bound progesterone receptors are expressed and regulated by estradiol and progesterone.