Regulation of Cervical Mucus Secretion
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ClinicalTrials.gov Identifier: NCT02969590 |
Recruitment Status :
Completed
First Posted : November 21, 2016
Results First Posted : October 18, 2019
Last Update Posted : October 18, 2019
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Condition or disease | Intervention/treatment | Phase |
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Fertility Contraception | Drug: Leuprolide acetate Drug: Estrogen and Progesterone Replacement Drug: Progestin | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 5 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | Single (Investigator) |
Primary Purpose: | Basic Science |
Official Title: | Regulation of Cervical Mucus Secretion |
Actual Study Start Date : | March 29, 2015 |
Actual Primary Completion Date : | August 23, 2017 |
Actual Study Completion Date : | August 23, 2017 |

Arm | Intervention/treatment |
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No Intervention: No Intervention: Spontaneous Cycle (1 month)
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).
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Active Comparator: NET Arm - Norethindrone (4 months)
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. |
Drug: Leuprolide acetate
Following this spontaneous cycle, participants received a single intramuscular injection of leuprolide acetate (11.25mg, LupronVR; Abbvie, Chicago, IL), a dose documented to suppress ovarian function for at least 3 months. Ovarian suppression is confirmed with serum E2 less than or equal to 35 pg/ml 21-28 day post-injection.
Other Name: Lupron Drug: Estrogen and Progesterone Replacement Replace hormones exogenously to create an artificial cycle
Other Names:
Drug: Progestin Synthetic progestin to assess effects on cervical mucus.
Other Names:
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Active Comparator: E2WD Arm - Estradiol (4 months)
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. |
Drug: Leuprolide acetate
Following this spontaneous cycle, participants received a single intramuscular injection of leuprolide acetate (11.25mg, LupronVR; Abbvie, Chicago, IL), a dose documented to suppress ovarian function for at least 3 months. Ovarian suppression is confirmed with serum E2 less than or equal to 35 pg/ml 21-28 day post-injection.
Other Name: Lupron Drug: Estrogen and Progesterone Replacement Replace hormones exogenously to create an artificial cycle
Other Names:
Drug: Progestin Synthetic progestin to assess effects on cervical mucus.
Other Names:
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- Median Cervical Mucus Score - Baseline [ Time Frame: Baseline ]Measurement of median cervical mucus scores at baseline. The current clinical standard for appraising cervical mucus is the cervical mucus score (ie. Insler score) that examines mucus based on 5 metrics including volume, spinnbarkeit (stretch), ferning, viscosity and cellularity on a 15-point scale. Per WHO guidelines, scores above 10 are considered "mucus favoring penetration" and scores below 10 are considered to be "unfavorable to penetration."
- Sperm Penetration Scores [ Time Frame: Approximately one year ]Measuring sperm penetration scores in different hormonal conditions
- Median Cervical Mucus Score - 2 Hour [ Time Frame: 2 hours ]Measurement of median cervical mucus scores 2 hours following norethindrone administration. The current clinical standard for appraising cervical mucus is the cervical mucus score (ie. Insler score) that examines mucus based on 5 metrics including volume, spinnbarkeit (stretch), ferning, viscosity and cellularity on a 15-point scale. Per WHO guidelines, scores above 10 are considered "mucus favoring penetration" and scores below 10 are considered to be "unfavorable to penetration."
- Median Cervical Mucus Score - 6 Hour [ Time Frame: 6 hours ]Measurement of median cervical mucus scores 6 hours following norethindrone administration. The current clinical standard for appraising cervical mucus is the cervical mucus score (ie. Insler score) that examines mucus based on 5 metrics including volume, spinnbarkeit (stretch), ferning, viscosity and cellularity on a 15-point scale. Per WHO guidelines, scores above 10 are considered "mucus favoring penetration" and scores below 10 are considered to be "unfavorable to penetration."
- Median Cervical Mucus Score - 24 Hour [ Time Frame: 24 hours ]Measurement of median cervical mucus scores 24 hours following norethindrone administration. The current clinical standard for appraising cervical mucus is the cervical mucus score (ie. Insler score) that examines mucus based on 5 metrics including volume, spinnbarkeit (stretch), ferning, viscosity and cellularity on a 15-point scale. Per WHO guidelines, scores above 10 are considered "mucus favoring penetration" and scores below 10 are considered to be "unfavorable to penetration."
- Change in PGRMC1 During Menstrual Cycle [ Time Frame: 1 month ]
Measuring the mean transcript change of membrane bound progestin receptors (PGRMC1) from follicular phase to ovulation to luteal phase of spontaneous menstrual cycle.
Total RNA (ribonucleic acid) was isolated from endocervical cell samples and analyzed for expression of PGRMC1 using real-time PCR (polymerase chain reaction) relative to levels of ribosomal (S10) RNA. An endocervical brush will be inserted into the os and then immediately rinsed into a special RNA preserving reagent. After total RNA is isolated and purified, it will be reverse transcribed into cDNA using primers.
Ratio of PGRMC1 to 18s RNA
Gene expression of membrane bound progesterone receptors in endocervical cells

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Ages Eligible for Study: | 21 Years to 40 Years (Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02969590
United States, Oregon | |
Oregon Health & Science University | |
Portland, Oregon, United States, 97239 |
Principal Investigator: | Leo Han, MD | Oregon Health and Science University |
Documents provided by Leo Han, Oregon Health and Science University:
Responsible Party: | Leo Han, Instructor, Oregon Health and Science University |
ClinicalTrials.gov Identifier: | NCT02969590 |
Other Study ID Numbers: |
OHSU IRB 11532 |
First Posted: | November 21, 2016 Key Record Dates |
Results First Posted: | October 18, 2019 |
Last Update Posted: | October 18, 2019 |
Last Verified: | October 2019 |
Contraception Mucus Cervix progestin hormones |
Leuprolide Norethindrone Estradiol Estrogens Progesterone Progestins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Contraceptive Agents, Hormonal |
Contraceptive Agents Reproductive Control Agents Contraceptive Agents, Female Fertility Agents, Female Fertility Agents Antineoplastic Agents, Hormonal Antineoplastic Agents Contraceptives, Oral, Hormonal Contraceptives, Oral Contraceptives, Oral, Synthetic |