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
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.
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label
In healthy subjects, the acute changes in FSH, inhibin A, inhibin B and estradiol between the Letrozole and control cycles at each cycle stage
end of control and treatment cycles
Janet E Hall, M.D.
Massachusetts General Hospital
United States: Food and Drug Administration
|Reproductive Endocrine Unit, Massachusetts General Hospital||Boston, Massachusetts 02114|