Journal
FERTILITY AND STERILITY
Volume 95, Issue 6, Pages 2063-2066Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2011.01.158
Keywords
Aromatase inhibitor; hypothalamic-pituitary-gonadal axis; letrozole; luteinizing hormone; ovary; pituitary
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Funding
- NIH [K24 041978, U54 HD058155]
- CTSA [RR 0257-48-50, UL1 RR025750, KL2 RR025749]
- National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [TL1 RR025748]
- NIH Roadmap for Medical Research
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Objective: To better understand the site and mode of action of aromatase inhibitors. Design: Prospective study. Setting: Academic research environment. Patient(s): Five eumenorrheic (without polycystic ovary syndrome), early follicular phase women with a normal body mass index (mean: 20.47 +/- 0.68 kg/m(2)), and 12 normal weight, midreproductive aged, early follicular phase women with a normal body mass index (mean: 20.8 +/- 1.7 kg/m(2)) as historical controls. Intervention(s): 2.5 mg letrozole daily for 7 days, with daily urine collection (first morning void), thrice weekly blood sampling, and 4 hours of blood sampling every 10 minutes. Main Outcome Measure(s): Serumluteinizing hormone (LH) measured by a well-characterized immunofluorometric assay with LH pulse characteristics compared between treated and control groups using t tests. Result(s): Mean LH and LH pulse amplitude more than doubled in the women who had taken letrozole compared with the controls, but the LH pulse frequency did not differ between the women taking letrozole and the controls. Conclusion(s): These results indicate that the release of negative feedback inhibition of estradiol on the hypothalamic-pituitary axis in normal women by aromatase inhibitors creates an amplitude-related increase in endogenous hypothalamic-pituitary drive. The finding that the mean LH and LH pulse amplitude, but not the frequency, increased after letrozole suggests a possible pituitary site of action. (Fertil Steril (R) 2011; 95:2063-6. (C) 2011 by American Society for Reproductive Medicine.)
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