Letrozole Treatment in Normal and GnRH Deficient Women

NCT ID: NCT00351416

Last Updated: 2017-07-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-21

Brief Summary

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.

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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

Letrozole 20 mg orally one time

NAL-GLU GnRH antagonist

Intervention Type: DRUG

5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously

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.

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

Letrozole 20 mg orally one time

NAL-GLU GnRH antagonist

Intervention Type: DRUG

5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously

Interventions

Letrozole

Letrozole 20 mg orally one time

Intervention Type: DRUG

NAL-GLU GnRH antagonist

5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously

Intervention Type: DRUG

Other Intervention Names

aromatase inhibitor; Femara; GnRH antagonist

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Janet E. Hall, MD

Associate Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Janet E Hall, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Reproductive Endocrine Unit, Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

Sundry Department Fund

Identifier Type: OTHER

Identifier Source: secondary_id

2003-P-001895

Identifier Type: -

Identifier Source: org_study_id