Clinical trial NCT01602679: Acute Effects of Progesterone on LH Pulses During the Follicular Phase (CRM006)
Official title: Acute Effects of Progesterone on LH Pulses During the Follicular Phase
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Female Reproductive Physiology
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2012-05-21
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, placebo-controlled, crossover study
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Change in Number of LH Pulses Per Hour
timeFrame: 10 hours following administration of micronized progesterone or placebo
Secondary outcomes:
measure: Change in Mean LH
timeFrame: 10 hours following administration of micronized progesterone or placebo
measure: Change in Mean LH Amplitude
timeFrame: 10 hours following administration of micronized progesterone or placebo
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: Center for Research in Reproduction
state: Virginia
Study officials:
affiliation: University of Virginia
name: Christopher R. McCartney, MD
role: PRINCIPAL_INVESTIGATOR
References: