Letrozole Treatment in Normal and GnRH Deficient Women

June 28, 2017 updated by: Janet E. Hall, MD, Massachusetts General Hospital

This research study involves the use of the drugs Letrozole, GnRH, and NAL-GLU GnRH antagonist. Letrozole is a drug that is approved by the U.S. Food and Drug Administration (FDA) for use in breast cancer treatment that has been found to block the formation of estrogen. The NAL-GLU GnRH antagonist is a drug that temporarily blocks the action of GnRH. GnRH is a hormone that the body makes that stimulates other hormones that then control the function of the ovary.

The purpose is to study the effects of the administration of letrozole in women with GnRH deficiency at the same time that they receive gonadotropin-releasing hormone (GnRH). In addition, administration of letrozole and NAL-GLU GnRH antagonist in healthy women with normal menstrual cycles will be done to evaluate the role of estrogen in the control of the hormone FSH, or Follicle Stimulating Hormone, in the female reproductive cycle. A better understanding of FSH control may help in the development of new treatments for women with difficulty conceiving.

Study Overview

Status

Unknown

Conditions

Detailed Description

The negative feedback control of FSH is crucial for the precise regulation of follicular development in the female. An important component of this feedback is exerted by estrogen. Letrozole will be used to block aromatase and therefore estradiol production in normal and GnRH deficient females. These studies will dissect the relative roles of estradiol and inhibin on FSH secretion at the pituitary and hypothalamus.

The aromatase inhibitors block aromatization of androgens to estrogens, allowing us to examine the relative contribution of estradiol and the inhibins to FSH regulation. The use of a submaximal dose of a GnRH antagonist will allow us to estimate the overall amount of GnRH secreted (hypothalamic contribution) with and without aromatase inhibition.

A more thorough understanding of estrogen and inhibin feedback on FSH will improve our understanding of the failure of follicle development in subsets of patients with infertility, such as polycystic ovary syndrome, in which FSH levels are normal but follicles fail to develop. Study of FSH control will also help us understand the failure of negative feedback on FSH, which can result in multiple follicular development and multiple gestation and its associated costs and risks. Thus, these studies may afford new therapeutic options for conception in infertile patients while simultaneously providing new methods to avoid the risks of multiple gestations.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Reproductive Endocrine Unit, Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 38 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

Healthy Normal Subjects will meet the following criteria:

  • 18 to 35 years of age
  • good general health
  • on no medications including any hormonal drug products for at least 3 months before the study
  • regular menstrual cycles every 25-35 days with ovulation documented by a luteal phase progesterone > 3 ng/ml
  • no evidence of androgen excess
  • normal TSH, prolactin and hemoglobin
  • use of double-barrier contraception, permanent sterilization or abstinence during the cycle of study.
  • Negative pregnancy test (serum) at the beginning of each cycle of study
  • Normal Liver Function Test

Exclusion Criteria:

  • History of liver and/or kidney disease
  • Substance or alcohol abuse
  • Hormone dependent neoplasia including breast cancer
  • Women who are trying to become pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aromatase inhibitor EFP

Letrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and

Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted.

Letrozole 20 mg orally one time
Other Names:
  • Femara
  • aromatase inhibitor
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
Other Names:
  • GnRH antagonist
Experimental: Aromatase inhibitor LFP

Letrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2.

Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted.

Letrozole 20 mg orally one time
Other Names:
  • Femara
  • aromatase inhibitor
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
Other Names:
  • GnRH antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FSH Level
Time Frame: EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm
Difference in FSH peak following letrozole administration compared with control cycle
EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 21, 2004

Primary Completion (Actual)

June 29, 2009

Study Registration Dates

First Submitted

July 10, 2006

First Submitted That Met QC Criteria

July 10, 2006

First Posted (Estimate)

July 12, 2006

Study Record Updates

Last Update Posted (Actual)

July 27, 2017

Last Update Submitted That Met QC Criteria

June 28, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Once published, de-identified individual level data will be shared upon request to the PI.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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