Aromatase Inhibition Causes Increased Amplitude, but Not Frequency, of Hypothalamic-pituitary Output in Normal Women

Overview

Journal Fertil Steril

Specialty Reproductive Medicine

Date 2011 Mar 1

PMID 21353673

Citations 5

Authors

Alexander Kucherov

Alex J Polotsky

Marie Menke

Barbara Isaac

Beth McAvey

Erkan Buyuk

Andrew P Bradford

Cheryl Hickmon

Beatrice Babbs

Sarah Berga

Tammy Loucks

Nanette Santoro

Affiliations

Soon will be listed here.

Abstract

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/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.

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): Serum luteinizing 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.

Citing Articles

Plasticity of Anterior Pituitary Gonadotrope Cells Facilitates the Pre-Ovulatory LH Surge.

Clay C, Cherrington B, Navratil A Front Endocrinol (Lausanne). 2021; 11:616053.

PMID: 33613451 PMC: 7890248. DOI: 10.3389/fendo.2020.616053.

Aromatase Inhibition Ameliorates Decreased LH Output Found in Obese Women.

Jones K, Ryan S, Carlson N, Chosich J, Bradford A, Santoro N Reprod Sci. 2020; 27(4):1018-1023.

PMID: 32046430 PMC: 7142050. DOI: 10.1007/s43032-019-00105-5.

Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys.

Kenealy B, Keen K, Garcia J, Kohlenberg L, Terasawa E Proc Natl Acad Sci U S A. 2017; 114(52):13804-13809.

PMID: 29229849 PMC: 5748216. DOI: 10.1073/pnas.1716097115.

Extraovarian gonadotropin negative feedback revealed by aromatase inhibition in female marmoset monkeys.

Kraynak M, Flowers M, Shapiro R, Kapoor A, Levine J, Abbott D Am J Physiol Endocrinol Metab. 2017; 313(5):E507-E514.

PMID: 28679622 PMC: 5792143. DOI: 10.1152/ajpendo.00058.2017.

Profound reduction of ovarian estrogen by aromatase inhibition in obese women.

Ross L, Polotsky A, Kucherov A, Bradford A, Lesh J, Chosich J Obesity (Silver Spring). 2014; 22(6):1464-9.

PMID: 24482405 PMC: 4037337. DOI: 10.1002/oby.20713.

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