| Registry | NCT02969590 |
|---|---|
| Status | Completed |
| Phase | Phase 4 |
| Study type | Interventional; randomized, crossover, masking: single, basic science |
| Enrollment | 5 (Actual) |
| Sponsor | Oregon Health and Science University (Other); collaborators: Society of Family Planning |
| Conditions | Fertility, Contraception |
| Interventions | Leuprolide acetate, Estrogen and Progesterone Replacement, Progestin (Drug) |
| Dates | start 2015-03-29, primary completion 2017-08-23, completion 2017-08-23, first posted 2016-11-21, last updated 2019-10-18 |
| Locations | 1 site in United States |
Related Papers Related Patents Related Grants Related Experts
All trials for Fertility All trials for Contraception All trials of Leuprolide acetate All trials of Estrogen and Progesterone Replacement
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| No Intervention: Spontaneous Cycle (1 month) | No intervention | In order to qualify for the intervention phase, subjects needed to demonstrate favorable mucus at ovulation (Insler score of greater than or equal to 10 within 24h of an LH surge) and progesterone level in the luteal phase consistent with ovulation (a single P4 of greater than or equal to 3ng/ ml between days 18-35 of menstrual cycle). | |
| NET Arm - Norethindrone (4 months) | Active comparator | Drug: Leuprolide acetate; Drug: Estrogen and Progesterone Replacement; Drug: Progestin | This arm will receive Norethindrone (NET) first then experience estradiol withdrawal (E2WD). On the day prior to each admission, we instructed subjects to apply three fresh estradiol (E2) patches (0.3mg/day) to achieve mid-cycle level E2 effects. On the day of the first and third admission, subjects were randomized to the experimental condition, either: (1) oral progestin administration (e.g., a single dose of 0.35mg norethindrone) with continuation of the E2 patches; or (2) estradiol withdrawal (e.g., removal of the patches). Subject then received the converse intervention for admissions two and four. Subjects resumed treatment with the 0.1mg E2 patch until their next scheduled inpatient assessment. We required a minimum of five days at this level before repeating the dose escalation and the next evaluation. |
| E2WD Arm - Estradiol (4 months) | Active comparator | Drug: Leuprolide acetate; Drug: Estrogen and Progesterone Replacement; Drug: Progestin | This arm will experience estradiol withdrawal (E2WD) first and then receive Norethindrone (NET). On the day prior to each admission, we instructed subjects to apply three fresh estradiol (E2) patches (0.3mg/day) to achieve mid-cycle level E2 effects. On the day of the first and third admission, subjects were randomized to the experimental condition, either: (1) oral progestin administration (e.g., a single dose of 0.35mg norethindrone) with continuation of the E2 patches ; or (2) estradiol withdrawal (e.g., removal of the patches). Subject then received the converse intervention for admissions two and four. Subjects resumed treatment with the 0.1mg E2 patch until their next scheduled inpatient assessment. We required a minimum of five days at this level before repeating the dose escalation and the next evaluation. |
Sex: Female, ages: 21 Years to 40 Years, accepts healthy volunteers
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)
| Milestone | Spontaneous Cycle | NET Arm - Norethindrone, Then Estradiol Withdrawal | E2WD Arm - Estradiol Withdrawal, Then Norethindrone |
|---|---|---|---|
| Started | 5 | 0 | 0 |
| Completed | 4 | 0 | 0 |
| Not completed | 1 | 0 | 0 |
Time frame: 4 months
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Spontaneous Cycle | 0/5 (0.0%) | 0/5 (0.0%) | 0/5 (0.0%) |
| Norethindrone (NET) | 0/4 (0.0%) | 0/4 (0.0%) | 0/4 (0.0%) |
| Estradiol (E2) | 0/4 (0.0%) | 0/4 (0.0%) | 0/4 (0.0%) |
| Facility | City | Country | Status |
|---|---|---|---|
| Oregon Health & Science University | Portland, Oregon | United States |