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Ovulation DisorderPhase 4NCT01999569

The Role of Estrogen in Luteinizing Hormone Surge and Ovulation

A Phase 4 study testing Letrozole in people with Ovulation Disorder and Ovarian Cysts, run by Wake Forest University Health Sciences at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for
Ovulation Disorder, Ovarian Cysts
What is being tested?
Letrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Apr 2007to May 2008
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Women's Institute at Carolinas Medical Center

    Charlotte, North Carolina, 28204

Other trials in United States

About this study

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.

Read the 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.

Being tested
Letrozole
Medical subject headings
Ovarian Cysts

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LetrozoleDrug

    Also called Femara

    Letrozole administered daily through the time of ovulation.

Study groups in NCT01999569
Study groupRoleWhat they receive
ControlNo interventionControl cycle. No intervention.
LetrozoleExperimental5mg daily
Receives: Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Progesterone Level Greater Than 1.5 ng/mL

    Serum progesterone ng/mL drawn during cycle days twelve through 22

    Measured: Cycle days 12-22

Secondary outcomes (2)

  1. Number of Participants With a Positive LH Test

    Urine ovulation tests assessed

    Measured: Cycle days 10-18

  2. Number of Participants With Follicular Development

    Ovulation; elevated progesterone

    Measured: Cycle day 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2013 (estimated)
  2. Study startApr 2007
  3. Primary completionMay 2008
  4. Study completionMay 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Single group
Masking
Triple blind
Who is masked
Care provider, Investigator, Outcomes assessor
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01999569
Sponsor's protocol ID
LH-2013
Status last verified
Oct 2021
First submitted
26 Nov 2013
Last updated
22 Apr 2022
Data monitoring committee
No
Individual data sharing
No

Publications

  • Christensen A, Bentley GE, Cabrera R, Ortega HH, Perfito N, Wu TJ, Micevych P. Hormonal regulation of female reproduction. Horm Metab Res. 2012 Jul;44(8):587-91. doi: 10.1055/s-0032-1306301. Epub 2012 Mar 21.

    PubMed 22438212

  • Morioka N, Zhu C, Brannstrom M, Woessner JF, LeMaire WJ. Mechanism of mammalian ovulation. Prog Clin Biol Res. 1989;294:65-85.

    PubMed 2657783

  • Goh HH, Ratnam SS. The LH surge in humans: its mechanism and sex difference. Gynecol Endocrinol. 1988 Jun;2(2):165-82. doi: 10.3109/09513598809023624.

    PubMed 3055821

  • Laven JS, Fauser BC. What role of estrogens in ovarian stimulation. Maturitas. 2006 Jul 20;54(4):356-62. doi: 10.1016/j.maturitas.2006.04.022. Epub 2006 Jun 19.

    PubMed 16782289

  • Casper RF, Mitwally MF. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab. 2006 Mar;91(3):760-71. doi: 10.1210/jc.2005-1923. Epub 2005 Dec 29.

    PubMed 16384846

  • Mitwally MF, Casper RF. Aromatase inhibition reduces the dose of gonadotropin required for controlled ovarian hyperstimulation. J Soc Gynecol Investig. 2004 Sep;11(6):406-15. doi: 10.1016/j.jsgi.2004.03.006.

    PubMed 15350255

  • Burstein HJ, Griggs JJ, Prestrud AA, Temin S. American society of clinical oncology clinical practice guideline update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Oncol Pract. 2010 Sep;6(5):243-6. doi: 10.1200/JOP.000082. Epub 2010 Aug 6.

    PubMed 21197188

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Letrozole in people with Ovulation Disorder and Ovarian Cysts, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Progesterone Level Greater Than 1.5 ng/mL (time frame: Cycle days 12-22). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01999569, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.

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