Hyperestrogenism The Elephant in Klinefelter’s Syndrome

Photo Credit: William Daigneault

What is clear is that a condition of relative hyperestrogenism is present in these patients, since the estradiol/testosterone ratio is altered thanks to the lower concentrations of total serum testosterone in presence of normal serum estradiol. Accordingly, the results of this study confirm unequivocally the significant reduction in total serum testosterone in men with KS compared to controls which seems to be also responsible for the significant, higher estradiol/testosterone ratio in men with KS compared to control subjects.

Relative Hyperestrogenism in Klinefelter Syndrome


With this in view, the most important result of this study is the finding of a significant increase of the estradiol/testosterone ratio in men with KS compared to control
subjects, suggesting a clinical condition of testosterone deficiency coupled with relative estrogen excess. Currently, only a few studies provided direct evidence on the unbalanced estradiol/testosterone ratio in men with KS. This imbalance in circulating sex steroids is a peculiar characteristic of men with KS in whom serum estradiol is in the highest quartile of the normal range notwithstanding low circulating levels of its precursor testosterone.

Probably, the activity and expression of the aromatase enzyme is increased in these patients, but information about the underlying mechanism is still not available in the literature. It is known that elevated serum LH levels may increase aromatase activity leading to a relative increase of estradiol secretion from the testes, but to what extent this mechanism operates in men with KS is not known. There is only indirect evidence by in vitro study.

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