The hypogonadal-obesity cycle: role of aromatase in modulating the testosterone-estradiol shunt--a major factor in the genesis of morbid obesity

Med Hypotheses. 1999 Jan;52(1):49-51. doi: 10.1054/mehy.1997.0624.


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.

MeSH terms

  • Aromatase / metabolism*
  • Aromatase Inhibitors
  • Enzyme Inhibitors / therapeutic use
  • Estradiol / metabolism*
  • Humans
  • Hypogonadism / complications
  • Hypogonadism / drug therapy
  • Hypogonadism / metabolism*
  • Male
  • Models, Biological
  • Obesity, Morbid / complications
  • Obesity, Morbid / etiology*
  • Obesity, Morbid / metabolism*
  • Testosterone / metabolism*


  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Testosterone
  • Estradiol
  • Aromatase