Trial record 10 of 378 for:    Ovarian Cysts: Ovarian Cysts

The Role of Estrogen in Luteinizing Hormone Surge and Ovulation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Brad Hurst, Carolinas Healthcare System
ClinicalTrials.gov Identifier:
NCT01999569
First received: November 26, 2013
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

The purpose of the study is to establish that sustained estrogen levels are the driving force for the LH surge, and are thereby necessary for ovulation to occur. We predict that by reducing levels of circulating estrogen, letrozole, an aromatase inhibitor, will inhibit ovulation from occurring.


Condition Intervention Phase
Ovulation Disorder
ESTROGENS/RIFAMPIN [VA Drug Interaction]
Ovarian Cysts
Drug: Letrozole
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: The Role of Estrogen in Luteinizing Hormone Surge and Ovulation

Resource links provided by NLM:


Further study details as provided by Carolinas Healthcare System:

Primary Outcome Measures:
  • Increase in Progesterone level [ Time Frame: Cycle days 12-22 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in LH level [ Time Frame: Cycle days 10-18 ] [ Designated as safety issue: No ]
  • Follicular Development [ Time Frame: Cycle day 12 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: April 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control
Control cycle. No intervention.
Experimental: Letrozole
5mg daily
Drug: Letrozole
Letrozole administered daily through the time of ovulation.
Other Name: Femara

Detailed Description:

Sine the common understanding of ovulation in a natural cycle suggests that a sustained, elevated estradiol level is required to trigger the LH surge, administration of letrozole throughout the cycle should lower estradiol levels and prevent the LH surge from occurring. In this study, we sought to determine if the LH surge, ovulation and luteinization occurs in spite of low estradiol levels by daily administration of letrozole in a group of normal ovulatory volunteers in a prospective study.

After IRB approval and informed consent were obtained, ten willing volunteers that met inclusion criteria (no hormonal contraception within 3 months, regular menstrual cycles 26 - 30 days, normal thyroid function and normal prolactin, and no pregnancy currently or within 3 months) were monitored for one month without treatment for evaluation of normal ovulation.

Natural control cycle The subjects used home urine LH tests (Clearblue® Easy, SPD Swiss Precision Diagnostics, Switzerland) on days 10-18 to monitor for the LH surge in both the initial natural cycle and the letrozole cycle. Blood was drawn every other day starting on day 12 of the cycle through day 22 to measure estradiol and progesterone levels, and follicular development was monitored using transvaginal ultrasound on cycle day 12-14.

Letrozole cycle In the next cycle, all ten subjects were administered oral letrozole 5 mg daily (Femara®, Novartis Pharmaceuticals Corporation, East Hanover, NJ ) starting on cycle day 1-3 and continuing through the completion of the study (cycle day 22). Once again, serum estradiol and progesterone levels were measured every other day on days 12-22. The development of the ovarian follicles was monitored by transvaginal ultrasound once in each cycle between days 12-14, and LH surge was monitored with home urine ovulation tests on days 10-18. Table 1 illustrates protocols for both the natural control cycle and the letrozole study cycle.

The primary outcome, assessment of ovulation in letrozole cycles, was determined by the presence or absence of progesterone elevation (>1.5 ng/mL) and the presence or absence of a positive urinary LH test. The bioequivalence evaluation of two cycles (before and after letrozole administration) was based on pharmacokinetic parameters such as area under the serum concentration-time curve (AUC), the peak serum concentration (Cmax) and the time of peak serum concentration (Tmax). Cmax and Tmax were determined by visual inspection from each volunteer's serum concentration-time curve for estradiol and progesterone. AUC was calculated by the linear trapezoidal method from day 12 through day 22 in both the initial natural cycle and the letrozole cycle.

Paired t-tests, or Wilcoxon Signed Rank tests if non-normally distributed, were used to evaluate the statistical significance of the mean values of the pharmacokinetic parameters. The McNemar test was used to assess the difference in LH surge and follicular development before and after letrozole administration. A standard of statistical significance (alpha) of 0.05 was used in all cases. The SAS System (SAS Institute, Cary, NC) was used for all analyses.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patient having regular menstrual cycles between 26-30 days
  • Ages 18-40
  • Patient must not be sexually active during the study period, or if so must be using a reliable form of non-hormonal birth control including tubal ligation or vasectomy, non-hormonal intrauterine contraceptive device (IUD), or condoms with spermicide.
  • Willing to participate in study and available for all monitoring visits.
  • IRB consent

Exclusion Criteria:

  • Patient must NOT have used hormonal contraception three months or less prior to study.
  • Irregular menstrual cycles (<26 days or >30 days within the last 6 months.
  • Untreated thyroid dysfunction or hyperprolactinemia
  • Pregnancy (current or within 3 months) or breastfeeding
  • Allergy or contraindication to letrozole
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01999569

Locations
United States, North Carolina
Women's Institute at Carolinas Medical Center
Charlotte, North Carolina, United States, 28204
Sponsors and Collaborators
Carolinas Healthcare System
Investigators
Principal Investigator: Brad S Hurst, MD Carolinas Healthcare System
  More Information

Publications:
Responsible Party: Brad Hurst, Director of Assisted Reproduction, Carolinas Healthcare System
ClinicalTrials.gov Identifier: NCT01999569     History of Changes
Other Study ID Numbers: LH-2013
Study First Received: November 26, 2013
Last Updated: August 4, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Ovarian Cysts
Cysts
Ovarian Diseases
Neoplasms
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Estrogens
Hormones
Letrozole
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 11, 2014