Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Letrozole Treatment in Normal and GnRH Deficient Women

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Janet E. Hall, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00351416
First received: July 10, 2006
Last updated: March 16, 2017
Last verified: March 2017
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
Drug: Letrozole
Drug: NAL-GLU GnRH antagonist
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
This is a physiologic study designed to investigate the relative roles of estradiol and inhibin A or inhibin B in the control of FSH secretion during normal menstrual cycles using an aromatase inhibitor. Subjects serve as their own control with no intervention in cycle 1 and letrozole administration in cycle 2. Subjects are studied in the early follicular phase or the late follicular phase.
Masking: No masking
Primary Purpose: Other
Official Title: Letrozole Treatment in Normal and GnRH Deficient Women

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • FSH Level [ Time Frame: matched cycle day ]
    Difference in FSH peak following letrozole administration compared with control cycle


Enrollment: 15
Study Start Date: July 2004
Estimated Study Completion Date: December 2018
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
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
  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: NCT00351416

Locations
United States, Massachusetts
Reproductive Endocrine Unit, Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Institutes of Health (NIH)
Investigators
Principal Investigator: Janet E Hall, M.D. Massachusetts General Hospital
  More Information

Responsible Party: Janet E. Hall, MD, Associate Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00351416     History of Changes
Other Study ID Numbers: 2003-P-001895
Sundry Department Fund ( Other Identifier: MGH-REU Department Fund )
Study First Received: July 10, 2006
Results First Received: March 16, 2017
Last Updated: March 16, 2017
Individual Participant Data  
Plan to Share IPD: No
Plan Description: Once published, de-identified individual level data will be shared upon request to the PI.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Massachusetts General Hospital:
GnRH deficiency
GnRH antagonist
Letrozole
GnRH
FSH
LH
Inhibins

Additional relevant MeSH terms:
Prolactin Release-Inhibiting Factors
Aromatase Inhibitors
Letrozole
LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 25, 2017