title: Aromatase inhibition causes increased amplitude, but not frequency, of hypothalamic-pituitary output in normal women.
abstract: OBJECTIVE
  To better understand the site and mode of action of aromatase inhibitors.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Academic research environment.
  
  
  METHODS
  Five eumenorrheic (without polycystic ovary syndrome), early follicular phase women with a normal body mass index (mean: 20.47±0.68 kg/m2), and 12 normal weight, midreproductive aged, early follicular phase women with a normal body mass index (mean: 20.8±1.7 kg/m2) as historical controls.
  
  
  METHODS
  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.
  
  
  METHODS
  Serum luteinizing hormone (LH) measured by a well-characterized immunofluorometric assay with LH pulse characteristics compared between treated and control groups using t tests.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Obstetrics and Gynecology and Women's Health, Division of Reproductive Endocrinology and Infertility, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kucherov
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Polotsky
authors.forename: Marie
authors.initials: M
authors.lastname: Menke
authors.forename: Barbara
authors.initials: B
authors.lastname: Isaac
authors.forename: Beth
authors.initials: B
authors.lastname: McAvey
authors.forename: Erkan
authors.initials: E
authors.lastname: Buyuk
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Bradford
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hickmon
authors.forename: Beatrice
authors.initials: B
authors.lastname: Babbs
authors.forename: Sarah
authors.initials: S
authors.lastname: Berga
authors.forename: Tammy
authors.initials: T
authors.lastname: Loucks
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
mesh_terms: D000293:Adolescent; D000328:Adult; D001141:Aromatase / Q000378:metabolism / Q000502:physiology; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D000077289:Letrozole; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism*; D011673:Pulsatile Flow / Q000187:drug effects* / Q000502:physiology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology; D055815:Young Adult
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D004958:Estradiol; D000077289:Letrozole; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001141:Aromatase