Acute Effects of Progesterone on LH Pulses During the Follicular Phase (CRM006)

NCT ID: NCT01602679

Last Updated: 2018-10-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2015-07-31

Brief Summary

The rapidity with which progesterone slows LH (and by inference GnRH) pulse frequency in women is unclear. The investigators hypothesize that progesterone slows LH pulse frequency within 10 hours. The investigators propose to assess this further with a randomized, cross-over, placebo-controlled study. Regularly cycling women without hyperandrogenism will be admitted to the Clinical Research Unit on cycle day 5-9 (mid-follicular phase) for a 10 hour frequent sampling study to observe LH, FSH, estradiol, progesterone, and testosterone. Either oral micronized progesterone suspension or placebo will be administered at 0900 h. During a subsequent menstrual cycle, subjects will undergo another study identical to the first except that oral progesterone will be exchanged for placebo or vice versa in accordance with a crossover design.

Detailed Description

The rapidity with which progesterone slows LH (and by inference GnRH) pulse frequency in women is unclear. The investigators hypothesize that progesterone slows LH pulse frequency within 10 hours. The investigators propose to assess this further with a randomized, cross-over, placebo-controlled study. Regularly cycling women without hyperandrogenism will be admitted to the Clinical Research Unit on cycle day 5-9 (mid-follicular phase) for a frequent sampling study. Beginning at 0900 h, blood for LH, FSH, estradiol, progesterone, and testosterone will be obtained over a 10-hour period. Either oral micronized progesterone (100 mg p.o.) suspension or placebo will be administered at 0900 h. During a subsequent menstrual cycle, subjects will undergo another study identical to the first except that oral progesterone will be exchanged for placebo or vice versa in accordance with a crossover design. The primary endpoint of interest is LH pulse frequency; the investigators will compare LH pulse frequency after progesterone administration to LH pulse frequency after placebo administration.

Conditions

Female Reproductive Physiology

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

micronized progesterone, then placebo

Participants first received oral micronized progesterone (100 mg p.o.) suspension. After a washout period of approximately 20 days, they then received placebo (matching oral micronized progesterone suspension).

Group Type: EXPERIMENTAL

oral micronized progesterone suspension

Intervention Type: DRUG

oral micronized progesterone (100 mg p.o.) suspension

Placebo

Intervention Type: DRUG

Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Placebo, then micronized progesterone

Participants first received placebo. After a washout period of approximately 20 days, they then received oral micronized progesterone syrup (100 mg p.o.)Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Group Type: PLACEBO_COMPARATOR

oral micronized progesterone suspension

Intervention Type: DRUG

oral micronized progesterone (100 mg p.o.) suspension

Placebo

Intervention Type: DRUG

Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Interventions

oral micronized progesterone suspension

oral micronized progesterone (100 mg p.o.) suspension

Intervention Type: DRUG

Placebo

Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Intervention Type: DRUG

Other Intervention Names

Progesterone

Eligibility Criteria

Inclusion Criteria

• Subjects will be healthy women with regular menstrual cycles and no evidence of hyperandrogenism.
• Subjects will be 18-30 years old; the investigators use a cutoff age of 30 years because age-related alterations in the hypothalamic-pituitary-ovarian axis is uncommon before age 30 years.
• Subjects will be willing to strictly avoid pregnancy (using non-hormonal methods) during the time of study and must be willing and able to provide informed consent.

Exclusion Criteria

• Pregnancy
• Lactation
• History of allergy to progesterone
• BMI < 18 kg/m2 or > 30 kg/m2 (underweight and obesity can affect hypothalamic-pituitary-ovarian function)
• Excessive exercise, defined as routine and current engagement in either (a) moderate exercise (e.g., brisk walking) exceeding 14 hours per week or (a) vigorous exercise exceeding 7 hours a week.
• Clinical hyperandrogenism (primarily hirsutism)
• Abnormally elevated free testosterone or DHEAS concentration
• A previous diagnosis of diabetes, a fasting glucose ≥ 126 mg/dl
• Abnormal TSH (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded; or, for a new diagnosis of hypothyroidism, further study will at the least be delayed pending appropriate treatment) (confirmed on repeat)
• Abnormal prolactin (confirmed on repeat)
• Evidence of Cushing's syndrome by history or physical exam
• History of venous thromboembolism, breast/ovarian/endometrial cancer
• The investigators will exclude women with any other cancer diagnosis and/or treatment (with the exception of basal cell or squamous skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years.
• Women with anemia (hematocrit < 36% and hemoglobin level < 12 g/dl) will be treated with iron for a maximum of 2 sequential months before the 1st admission and/or before the 2nd admission. If they remain anemic after 2 sequential months of ferrous gluconate (325 mg bid), they will then be excluded from further participation in the study.
• Women with a significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; known or suspected coronary atherosclerosis; asthma requiring systemic intermittent corticosteroids; etc.) will be excluded.
• Women with liver enzymes, alkaline phosphatase, or bilirubin > 1.5 times upper limit of normal (confirmed on repeat) will be excluded, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome.
• Abnormal sodium or potassium concentrations (confirmed on repeat); bicarbonate concentrations <20 or >30 (confirmed on repeat)
• Women with abnormal renal function (i.e., serum creatinine > 1.4) will be excluded (confirmed on repeat)
• Due to the amount of blood being drawn in the study, subjects with body weight < 110 pounds will be excluded from the study
• Being a study of the acute effects of progesterone on the hypothalamic-pituitary unit, subjects must not take hormonal medications (e.g., oral contraceptives) or other medications known to affect the reproductive axis for 60 days prior to the study and during the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Chris McCartney

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher R. McCartney, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

Center for Research in Reproduction

Charlottesville, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01HD058671

Identifier Type: NIH

Identifier Source: secondary_id

View Link

16085

Identifier Type: -

Identifier Source: org_study_id