Determining How Quickly Progesterone Slows LH Pulse Frequency

NCT00594217 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 13368R01HD058671
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

The rapidity with which progesterone (P) suppresses daytime lutenizing hormone (LH) (and by inference gonadotropin releasing hormone (GnRH)) pulse frequency is unknown. We propose to assess this further using a randomized, cross-over, placebo-controlled study. Ovulatory women will begin E2 patches on day 4-8 of the cycle, while women with PCOS will begin E2 patches either on day 4-8 of the cycle or at least 8 weeks post-menses. After 3 d of E2 administration, women will undergo a 24-h sampling study in the GCRC. Beginning at 2000 h, blood for LH, FSH, E2, P, and T will be obtained over a 24-h period. After 10 h of sampling, either oral micronized P (100 mg p.o.) suspension or placebo suspension will be administered (according to randomization). At the completion of sampling, E2 patches will be discontinued. During a subsequent menstrual cycle (or after at least 3 weeks in oligomenorrheic PCOS), subjects will undergo another GCRC study identical to the first (including pretreatment with E2) except that oral P will be exchanged for placebo or vice versa in accordance with the crossover design. We will assess the acute effects of progesterone on LH frequency, with secondary endpoints being mean LH, LH pulse amplitude, and mean follicle-stimulating hormone (FSH). We propose two primary hypotheses: (1) administration of P (at 0600 h) to normally cycling adult women during the follicular phase will result in a demonstrable suppression of daytime LH (and by inference GnRH) pulse frequency within 12 hours; (2) administration of P (at 0600 h) to women with PCOS will result in less suppression of daytime LH pulse frequency than in ovulatory women without PCOS. A secondary hypothesis is that augmentation of LH amplitude after P administration will be less in PCOS compared to normal controls.

Conditions

Normal; PCOS

Keywords

PCOS

Outcome Measures

Primary Outcomes (1)

• LH Pulse Frequency

  The primary endpoint is the change in the number of LH pulses (over 10 hours) attributable to progesterone.

  10 hours before and after administration of micronized progesterone and placebo

Secondary Outcomes (3)

• Mean LH

  10 hours before and after administration of micronized progesterone and placebo

• LH Pulse Mass

  10 hours before and after administration of micronized progesterone and placebo

• Mean FSH

  10 hours before and after administration of micronized progesterone and placebo

Study Arms (2)

PCOS women

EXPERIMENTAL

PCOS women: women were considered to have PCOS if they had evidence of clinical and/or biochemical hyperandrogenism plus oligo-/amenorrhea in the absence of other identifiable causes.

Drug: oral micronized progesterone suspension; Other: Placebo

Normal Controls

ACTIVE COMPARATOR

Normal control women: women with regular menstrual cycles without evidence of hyperandrogenism.

Drug: oral micronized progesterone suspension; Other: Placebo

Interventions

oral micronized progesterone suspension DRUG

oral micronized progesterone suspension, single 100 mg oral dose

Also known as: progesterone

Normal Controls; PCOS women

Placebo OTHER

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

Normal Controls; PCOS women

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects will be healthy women in two groups: (1) women with regular menstrual cycles and no evidence of hyperandrogenism, and (2) women with PCOS (defined as clinical/biochemical evidence of hyperandrogenism plus oligomenorrhea, but with no evidence for other endocrinopathies).
• Subjects will be 18-35 years old.
• 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.

You may not qualify if:

• We will exclude women with a history of any disorders that may potentially be complicated by hormonal treatment, such as DVT and breast, ovarian, or endometrial cancer.
• We 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/or a 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 history of any disorders that may potentially be complicated by long-term iron supplementation, such as hemochromatosis and polycythemia vera, will be excluded.
• 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)
• Pregnant and breast-feeding women will be excluded.
• Women with a BMI greater or equal to 40 kg/m2.
• Virilization
• A total testosterone \> 150 ng/dl in women with PCOS (which suggests the possibility of a virilizing neoplasm) (confirmed on repeat)
• Elevated DHEAS (mild elevations may be seen in PCOS, and elevations \< 1.5 times the upper limit of normal will be accepted in PCOS) (confirmed on repeat)
• Follicular 17-hydroxyprogesterone \> 300 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase and there is a concern about the possibility of congenital adrenal hyperplasia, the 17-hydroxyprogesterone may be collected during the follicular phase, or \>60 if oligomenorrheic). NOTE: If a 17-hydroxyprogesterone \> 300 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone \< 1000 ng/dl will be required for study participation.
• A previous diagnosis of diabetes, a fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c \> 6.5%

Sponsors & Collaborators

• University of Virginia: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Interventions

Progesterone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Limitations and Caveats

Results of this study have been published and are publicly available at https://pmc.ncbi.nlm.nih.gov/articles/PMC8981178/

Results Point of Contact

• Title: Dr. Christopher R. McCartney
• Organization: University of Virginia Center for Research in Reproduction

cm2hq@virginia.edu

4342436911

Study Officials

• Christopher McCartney, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Randomized, placebo-controlled, crossover study

Study Record Dates

• First Submitted: January 4, 2008
• First Posted: January 15, 2008
• Study Start: November 29, 2007
• Primary Completion: January 18, 2020
• Study Completion: January 18, 2020
• Last Updated: March 28, 2025
• Results First Posted: March 28, 2025

Record last verified: 2025-03

Locations

US (1)