Regulation of Cervical Mucus Secretion

Contraception Clinical Trial

Official title:

Regulation of Cervical Mucus Secretion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02969590
• Other study ID #: OHSU IRB 11532
• Status: Completed
• Phase: Phase 4
• Start date: March 29, 2015
• Est. completion date: August 23, 2017

Study information

• Verified date: October 2019
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: August 23, 2017
• Est. primary completion date: August 23, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 21 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Contraception
• Fertility

Intervention

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.
• Estrogen and Progesterone Replacement
Replace hormones exogenously to create an artificial cycle
• Progestin
Synthetic progestin to assess effects on cervical mucus.

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Oregon Health and Science University	Society of Family Planning

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Cervical Mucus Score - 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."	Baseline
Primary	Sperm Penetration Scores	Measuring sperm penetration scores in different hormonal conditions	Approximately one year
Primary	Median Cervical Mucus Score - 2 Hour	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."	2 hours
Primary	Median Cervical Mucus Score - 6 Hour	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."	6 hours
Primary	Median Cervical Mucus Score - 24 Hour	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."	24 hours
Secondary	Change in PGRMC1 During Menstrual Cycle	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	1 month