Overview

This trial is active, not recruiting.

Conditions kallmann's syndrome, hypogonadotropic hypogonadism, healthy volunteers
Treatments letrozole, nal-glu gnrh antagonist, gnrh
Phase phase 2/phase 3
Sponsor Massachusetts General Hospital
Collaborator National Institutes of Health (NIH)
Start date July 2004
End date December 2011
Trial size 70 participants
Trial identifier NCT00351416, 2003-P-001895, Sundry Department Fund

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model parallel assignment
Masking open label
Arm
(Other)
Early-follicular phase of the menstrual cycle
letrozole
Letrozole 20mg orally one time
nal-glu gnrh antagonist
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
gnrh
For GnRH-deficient subjects only: 75 ng/kg GnRH IV
(Other)
Late follicular phase of the menstrual cycle
letrozole
Letrozole 20mg orally one time
nal-glu gnrh antagonist
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
gnrh
For GnRH-deficient subjects only: 75 ng/kg GnRH IV
(Other)
Luteal phase of the menstrual cycle
letrozole
Letrozole 20mg orally one time
nal-glu gnrh antagonist
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
gnrh
For GnRH-deficient subjects only: 75 ng/kg GnRH IV

Primary Outcomes

Measure
In healthy subjects, the acute changes in FSH, inhibin A, inhibin B and estradiol between the Letrozole and control cycles at each cycle stage
time frame: end of control and treatment cycles
The average LH, FSH, inhibin A, inhibin B, estradiol and progesterone in the control and treatment cycles
time frame: end of control and treatment cycles
The number of pulses in 8 hrs and LH pulse amplitude will be compared in the control and treatment cycle
time frame: after each 16-hour admission
The percent suppression of LH will be compared in the control and Letrozole cycles
time frame: after each 16-hour admission

Eligibility Criteria

Female participants from 18 years up to 40 years old.

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 GnRH Deficient Subjects will meet the following criteria: - 18 to 40 years of age - good general health - on no gonadal replacement for at least 1 month before the study - GnRH deficiency (idiopathic hypogonadotropic hypogonadism or Kallmann's Syndrome, secondary hypothalamic amenorrhea, acquired hypogonadotropic hypogonadism) - normal TSH, prolactin and hemoglobin - use of double-barrier contraception or abstinence during the cycle of Letrozole administration - 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

Additional Information

Official title Letrozole Treatment in Normal and GnRH Deficient Women
Principal investigator Janet E Hall, M.D.
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 inhibin to FSH regulation. Using normal subjects and GnRH-deficient subjects receiving replacement GnRH allows us to compare the effect of relative estradiol blockade at the pituitary (GnRH deficient subjects) vs the pituitary and hypothalamus (normal subjects), thus determining the direct site of estradiol action. 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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2013.
Information provided to ClinicalTrials.gov by Massachusetts General Hospital.