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NCT00594217: CRM001

Determining How Quickly Progesterone Slows LH Pulse Frequency

Completed Phase 1 Results posted Last updated 28 March 2025
What this trial tests

Phase 1 trial testing oral micronized progesterone suspension in Normal in 85 participants. Completed in 18 January 2020.

Timeline
29 November 2007
Primary endpoint
18 January 2020
18 January 2020

Quick facts

Lead sponsorUniversity of Virginia
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingtriple
Primary purposeother
Enrollment85
Start date29 November 2007
Primary completion18 January 2020
Estimated completion18 January 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Virginia

Who can join

Adults 18 to 35, female only, with Normal or PCOS. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

LH Pulse Frequency Primary · 10 hours before and after administration of micronized progesterone and placebo

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

Placebo 20:00-06:00 (pre-pbo)
GroupValue95% CI
PCOS Women1.311.01 – 1.88
Normal Controls0.910.81 – 1.44
Placebo 10:00-20:00 (post-pbo)
GroupValue95% CI
PCOS Women1.331.24 – 1.85
Normal Controls1.191.04 – 1.52
Progesterone 20:00-06:00 (pre-P4)
GroupValue95% CI
PCOS Women0.990.80 – 1.85
Normal Controls0.980.86 – 1.44
Progesterone 10:00-20:00 (post-P4)
GroupValue95% CI
PCOS Women1.18.97 – 1.76
Normal Controls1.051.01 – 1.44
Mean LH Secondary · 10 hours before and after administration of micronized progesterone and placebo

A secondary endpoint is the change in mean LH concentration (over 10 hours) attributable to progesterone.

Placebo 20:00-06:00 (pre-pbo)
GroupValue95% CI
PCOS Women8.27.8 – 34.4
Normal Controls6.43.9 – 10.3
Placebo 10:00-20:00 (post-pbo)
GroupValue95% CI
PCOS Women12.09.6 – 36.0
Normal Controls8.87.1 – 16.5
Progesterone 20:00-06:00 (pre-P4)
GroupValue95% CI
PCOS Women8.67.6 – 18.1
Normal Controls5.62.5 – 17.6
Progesterone 10:00-20:00 (post-P4)
GroupValue95% CI
PCOS Women26.620.9 – 50.0
Normal Controls20.710.6 – 54.9
LH Pulse Mass Secondary · 10 hours before and after administration of micronized progesterone and placebo

A secondary endpoint is the change in LH pulse mass (a correlate of LH pulse amplitude) attributable to progesterone.

Placebo 20:00-06:00 (pre-pbo)
GroupValue95% CI
PCOS Women3.62.5 – 6.7
Normal Controls4.854.0 – 13.6
Placebo 10:00-20:00 (post-pbo)
GroupValue95% CI
PCOS Women4.32.9 – 8.2
Normal Controls7.515.3 – 26.4
Progesterone 20:00-06:00 (pre-p4)
GroupValue95% CI
PCOS Women3.61.7 – 11.1
Normal Controls5.473.8 – 15.8
Progesterone 10:00-20:00 (post-p4)
GroupValue95% CI
PCOS Women13.97.5 – 32.2
Normal Controls13.969.3 – 35.4
Mean FSH Secondary · 10 hours before and after administration of micronized progesterone and placebo

A secondary endpoint is the change in mean FSH concentration (over 10 hours) attributable to progesterone.

Placebo 20:00-06:00 (pre-pbo)
GroupValue95% CI
PCOS Women4.53.0 – 6.3
Normal Controls3.53.1 – 5.4
Placebo 10:00-20:00 (post-pbo)
GroupValue95% CI
PCOS Women3.93.3 – 9.0
Normal Controls4.53.8 – 7.0
Progesterone 20:00-06:00 (pre-p4)
GroupValue95% CI
PCOS Women4.23.0 – 6.4
Normal Controls4.42.5 – 5.9
Progesterone 10:00-20:00 (post-p4)
GroupValue95% CI
PCOS Women6.34.4 – 9.1
Normal Controls8.05.63 – 14.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected beginning after subjects began study drug/intervention/study-related procedures/specimen collection up until the end of the study drug/intervention/participation; an average of 6 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PCOS Women
Serious: 0/13 (0%)
Deaths: 0/13
Normal Controls
Serious: 0/16 (0%)
Deaths: 0/16
Other adverse events (5 terms — click to expand)

ReactionSystemPCOS WomenNormal Controls
SpottingReproductive system and breast disorders
nauseaGastrointestinal disorders
upper respiratory infectionRespiratory, thoracic and mediastinal disorders
fatigueGeneral disorders
swelling at IV siteSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT00594217 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Progesterone has rapid positive feedback actions on LH release but fails to reduce LH pulse frequency within 12 h in estradiol-pretreated women.
    Hutchens EG, Ramsey KA, Howard LC, Abshire MY, et al · · 2016 · cited 7× · PMID 27535481 · DOI 10.14814/phy2.12891
  2. Acute progesterone feedback on gonadotropin secretion is not demonstrably altered in estradiol-pretreated women with polycystic ovary syndrome.
    Kim SH, Lundgren JA, Patrie JT, Burt Solorzano CM, et al · · 2022 · cited 3× · PMID 35384387 · DOI 10.14814/phy2.15233

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Other recruiting trials for Normal

Currently open trials in the same condition.

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