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Completed

NCT Number: NCT02969590

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.

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Key information

Conditions

Fertility Contraception

Age range

21 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Oregon Health & Science University

Portland, Oregon, 97239, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Leuprolide Acetate

Drug

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 names: Lupron

Estrogen and Progesterone Replacement

Drug

Replace hormones exogenously to create an artificial cycle

Other names: Estradiol (vivelle-dot), Progesterone (prometrium, progestin)

Progestin

Drug

Synthetic progestin to assess effects on cervical mucus.

Other names: Norethindrone, NET

Primary outcomes

  1. 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."

  2. Sperm Penetration Scores

    Time frame: Approximately one year

    Measuring sperm penetration scores in different hormonal conditions

  3. 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."

  4. 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."

  5. 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."

Secondary outcomes

  1. 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

Sponsors and collaborators

Lead sponsor

Oregon Health and Science University

Other

Collaborators

  • Society of Family Planning

Registry information

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Nov 21, 2016
Registry last updated
Oct 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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