Influence of Letrozole and Anastrozole on Total Body Aromatization and Plasma Estrogen Levels in Postmenopausal Breast Cancer Patients Evaluated in a Randomized, Cross-Over Study
Abstract
PURPOSE: To compare the effects of the two novel, potent, nonsteroidal aromatase inhibitors anastrozole and letrozole on total-body aromatization and plasma estrogen levels. PATIENTS AND METHODS: Twelve postmenopausal women with estrogen receptor–positive, metastatic breast cancer were treated with anastrozole 1 mg orally (PO) and letrozole 2.5 mg PO once daily, each given for a time interval of 6 weeks in a randomized sequence. Total-body aromatization was determined before treatment and at the end of each treatment period using a dual-label isotopic technique involving isolation of the metabolites with high-performance liquid chromatography. Plasma levels of estrone (E 1 ), estradiol (E 2 ), and estrone sulfate (E 1 S) were determined in samples obtained before each injection using highly sensitive radioimmunoassays. RESULTS: Pretreatment aromatase levels ranged from 1.68% to 4.27%. On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole (mean percentage inhibition in the whole group, 97.3%) but in none of the 12 patients during treatment with letrozole (> 99.1% suppression in all patients; Wilcoxon, P = .0022, comparing the two drug regimens). Treatment with anastrozole suppressed plasma levels of E 1 , E 2 , and E 1 S by a mean of 81.0%, 84.9%, and 93.5%, respectrively, whereas treatment with letrozole caused a corresponding decrease of 84.3%, 87.8% and 98.0%, respectively. The suppression of E 1 and E 1 S was found to be significantly better during treatment with letrozole compared with anastrozole (P = .019 and .0037, respectively). CONCLUSION: This study revealed letrozole (2.5 mg once daily) to be a more potent suppressor of total-body aromatization and plasma estrogen levels compared with anastrozole (1 mg once daily) in postmenopausal women with metastatic breast cancer.
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Estrogen excess is associated with premature closure of the epiphyses.
“Estrogen excess in turn has been associated with premature closure of the epiphyses, gynecomastia and low gonadotropin and testosterone levels.”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [25]
Estrogen excess is associated with low testosterone levels.
“Estrogen excess in turn has been associated with premature closure of the epiphyses, gynecomastia and low gonadotropin and testosterone levels.”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [25]
Aromatase inhibitors effectively delay epiphysial maturation in boys.
“Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [25]
Estrogen excess is associated with gynecomastia.
“Estrogen excess in turn has been associated with premature closure of the epiphyses, gynecomastia and low gonadotropin and testosterone levels.”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [25]
Estrogen excess is associated with low gonadotropin levels.
“Estrogen excess in turn has been associated with premature closure of the epiphyses, gynecomastia and low gonadotropin and testosterone levels.”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [25]
This approach proved successful in rare conditions such as the aromatase-excess syndrome and high estrogen levels due to Sertoli cell tumors in boys with Peutz-Jeghers syndrome.
“This approach proved successful in rare conditions such as the aromatase-excess syndrome [25] and high estrogen levels due to Sertoli cell tumors in boys with Peutz-Jeghers syndrome [55].”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [25]
Estrogens are essential for epiphysial maturation in boys.
“Estrogens are essential for epiphysial maturation in boys.”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [25]
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- Authors
- Geisler, J., Haynes, B., Anker, G., Dowsett, M., & Lønning, P. E.
- Affiliations
- Haukeland University Hospital (NO)
- Venue
- Journal of Clinical Oncology
- Published
- 2002-02-01
- Volume
- 20
- Issue
- 3
- Pages
- 751-757
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2145819414
- Cited by
- 604
- References
- 37
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 8 · 2023: 15 · 2022: 10 · 2021: 11 · 2020: 14 · 2019: 14 · 2018: 12 · 2017: 18 · 2016: 25 · 2015: 23 · 2014: 26 · 2013: 22 · 2012: 16
- FWCI
- 25.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- letrozole, anastrozole, aromatase inhibitors, aromatization, plasma estrogen, estrone, estradiol, estrone sulfate, metastatic breast cancer, postmenopausal women, estrogen receptor-positive breast cancer, aromatase inhibition
- MeSH terms
- Letrozole, Anastrozole, Aged, Antineoplastic Agents, Aromatase, Breast Neoplasms, Chromatography, High Pressure Liquid, Enzyme Inhibitors, Estradiol, Estrogens, Estrone, Female, Humans, Middle Aged, Nitriles, Radioimmunoassay, Triazoles, Postmenopause, Cross-Over Studies, Antineoplastic Agents, Hormonal, Aromatase Inhibitors
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