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Acute Effects of Progesterone on LH Pulses During the Follicular Phase

This study is currently recruiting participants.
Verified January 2013 by University of Virginia
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Chris McCartney, University of Virginia
ClinicalTrials.gov Identifier:
NCT01602679
First received: May 17, 2012
Last updated: January 14, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention
Female Reproductive Physiology
 Drug: oral micronized progesterone suspension
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Acute Effects of Progesterone on LH Pulses During the Follicular Phase

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Change in number of LH pulses [ Time Frame: 10 hours following administration of micronized progesterone or placebo ] [ Designated as safety issue: No ]
    The primary endpoint is the change in the number of LH pulses (over 10 h), comparing (a) number of LH pulses at baseline to (b) number of LH pulses immediately after progesterone or placebo administration


Secondary Outcome Measures:
  • Change in mean LH [ Time Frame: 10 hours following administration of micronized progesterone or placebo ] [ Designated as safety issue: No ]
    This secondary endpoint is the change of the mean LH (over 10 h), comparing (a) mean LH at baseline to (b) mean LH immediately after progesterone or placebo administration

  • Change in mean LH amplitude [ Time Frame: 10 hours following administration of micronized progesterone or placebo ] [ Designated as safety issue: No ]
    This secondary endpoint is the change in the mean LH amplitude (over 10 h), comparing (a) mean LH amplitude at baseline to (b) mean LH amplitude immediately after progesterone or placebo administration


Estimated Enrollment: 36
Study Start Date: May 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: oral micronized progesterone suspension
oral micronized P (100 mg p.o.) suspension
 Drug: oral micronized progesterone suspension
oral micronized progesterone (100 mg p.o.) suspension
Placebo Comparator: Placebo
placebo
 Drug: Placebo
placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01602679

Contacts
Contact: Christopher R. McCartney, MD 434-243-6911 cm2hq@virginia.edu
Contact: Anne Gabel, MSc 434-243-6911 pcos@virginia.edu

Locations
United States, Virginia
Center for Research in Reproduction Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Anne Gabel, MSc     434-243-6911     pcos@virginia.edu    
Principal Investigator: Christopher R McCartney, MD            
Sponsors and Collaborators
University of Virginia
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Christopher R. McCartney, MD University of Virginia
  More Information

No publications provided

Responsible Party: Chris McCartney, Associate Professor of Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT01602679     History of Changes
Other Study ID Numbers: 16085, R01HD058671
Study First Received: May 17, 2012
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Progesterone
Progestins
Hormones
 Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013