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Letrozole Treatment in Normal and GnRH Deficient Women


Phase 2/Phase 3
18 Years
40 Years
Open (Enrolling)
Female
Kallmann's Syndrome, Hypogonadotropic Hypogonadism, Healthy Volunteers

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Trial Information

Letrozole Treatment in Normal and GnRH Deficient Women


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Outcome 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

Outcome Time Frame:

end of control and treatment cycles

Safety Issue:

No

Principal Investigator

Janet E Hall, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital

Authority:

United States: Food and Drug Administration

Study ID:

2003-P-001895

NCT ID:

NCT00351416

Start Date:

July 2004

Completion Date:

December 2011

Related Keywords:

  • Kallmann's Syndrome
  • Hypogonadotropic Hypogonadism
  • Healthy Volunteers
  • GnRH deficiency
  • GnRH antagonist
  • Letrozole
  • GnRH
  • FSH
  • LH
  • Inhibins
  • Hypogonadism
  • Kallmann Syndrome

Name

Location

Reproductive Endocrine Unit, Massachusetts General HospitalBoston, Massachusetts  02114