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The hypogonadal-obesity cycle: Role of aromatase in modulating the testosterone-estradiol shunt—A major factor in the genesis of morbid obesity
Abstract
Massive obesity in males is associated with decreased total and free testosterone levels as well as elevated estradiol levels. The decrease in testosterone occurs without the compensatory increases in gonadotropin and a progressive hypogonadotropic hypogonadal cycle develops. During the hypogonadal state, there is a preferential deposition of abdominal adipose tissue. With the increasing fatty-tissue accumulation, there is an increase of aromatase activity that is associated with a greater conversion of testosterone to estradiol (testosterone-estradiol shunt). This results in further depression of testosterone concentrations and leads to the increased preferential deposition of abdominal fat that, in turn, leads to a progressive hypogonadal state. Testalactone, an aromatase inhibitor, interrupts this cycle and repairs the depressed testosterone concentrations and decreases estradiol levels. This increases the testosterone levels and reverses the preferential deposition of abdominal fat, while increasing muscle protein and fat-free mass.
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“The first risk factor is constituted by adipose tissue expansion correlated to weight gain, which is linked to an overexpression of the enzyme aromatase. This enzyme converts Testosterone into Estradiol (Testosterone-Estradiol shunt) [15].”
From MOSH Syndrome (Male Obesity Secondary Hypogonadism): Clinical Assessment and Possible Therapeutic Approaches (2018) · cites this paper as [15]
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Metadata
- Authors
- Cohen, P. G.
- Corresponding author
- Cohen, P.G.
- Venue
- Medical Hypotheses
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 52
- Issue
- 1
- Pages
- 49-51
- ISSN
- 0306-9877 (ISSN-L)
- OpenAlex
- W1964441320
- Cited by
- 245
- References
- 13
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 12 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 16 · 2019: 24 · 2018: 15 · 2017: 14 · 2016: 7 · 2015: 16 · 2014: 12 · 2013: 17 · 2012: 9
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Hypotheses (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- aromatase, male obesity, hypogonadism, estradiol, abdominal fat deposition, aromatase inhibitors, fat-free mass, muscle proteins
- MeSH terms
- Aromatase, Enzyme Inhibitors, Estradiol, Humans, Hypogonadism, Male, Models, Biological, Obesity, Morbid, Testosterone, Aromatase Inhibitors
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