Regulation of Cervical Mucus Secretion

The purpose of this study is to help us determine how hormones impact the production of cervical mucus which is a fluid secreted by the opening of the uterus, also called the cervix. During a normal menstrual cycle, cervical mucus changes in response to two hormones that the ovaries make: estrogen and progesterone. Many of the birth control methods women use thicken mucus and make it less likely for sperm to enter the uterus. The goal of this study is to better understand the effects estrogen and progesterone have on the cervical mucus in the body. To do this, the investigators will be using a drug that suppresses natural hormone production for 3 months. Estrogen and progesterone will be artificially replaced to better understand their effects. The investigators will also be studying the effect of a common birth control pill that may work by thickening cervical mucus. Last, the investigators will study some of the cells in the cervix that produce mucus.

This proposed study is to evaluate the temporal changes in human cervical mucus in response to progesterone and progestins 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. To study this, a randomized, prospective, crossover study will be conducted by examining cervical mucus changes in a small cohort of women in whom investigators will suppress circulating hormonal levels by administering a GnRH antagonist. Investigators will then artificially replace Estrogen and Progesterone in order to differentiate their effects on clinical and laboratory measurements of mucus quality. The investigators will be looking closely at the immediate changes in mucus when .35 mg of norethindrone, a marketed drug is administered in this experimental setting. Cervical cell samples will also be collected at various time points and perform RT-PCR to determine whether genes for membrane bound progesterone receptor are expressed and regulated by Estrogen and Progesterone.

Eligibility Criteria:
Inclusion Criteria:

* Normal menstrual cycles of 25-35 days in length for at least previous 3 cycles
* 21-40 years of age
* BMI \>18, \<30
* Serum P4 ≥ 3 ng/ml on single sample collected between days 18-25 of self-reported menstrual cycle
* Flexible schedule allowing morning blood draws on less than 48 hour notice
* In good general health
* Commit to remain on stable diet during study period (no changes to normal dietary habits)
* Commit to using non-hormonal contraceptive methods during study period except those prescribed in the experimental protocol
* No objections to taking study drugs
* No objections to refraining from intercourse the night before any sampling and willing to using condoms during vaginal intercourse.

Exclusion Criteria:

* Oral contraceptive use or other hormone supplement within the preceding 2 months
* Women with current cervical infection
* Evidence of abnormal cervical cytology
* Use of Paragard IUD for contraception
* Long-acting hormonal contraceptive use in the past 12 months (e.g., Depo-Provera®)
* Contraindications to study drugs
* Current or past pregnancy within the previous 6 months or currently trying to conceive
* Desiring to conceive in the next 8 months
* Breastfeeding in the past 2 months
* Diagnosed Diabetes or Metabolic Syndrome
* Current or previous use of cholesterol lowering drugs within the preceding 12 months
* Diagnosed Polycystic Ovary Syndrome
* History of, or self-reported, substance abuse
* Smoker
* Previous infertility treatment excluding male factor issues
* Use of an investigational drug within the past 2 months
* History of excisional or ablative treatment procedure on cervix (ie. LEEP, Cryotherapy, Cold Knife Cone)