A Review on Testosterone: Estradiol Ratio—Does It Matter, How Do You Measure It, and Can You Optimize It?

There is a natural balance between the major sex steroids, testosterone and estradiol, controlled by gonadal secretion and peripheral conversion by aromatase. This balance is impacted by a variety of inborn and acquired conditions, and, more recently, by a growing use of exogenous testosterone therapy and off-label aromatase use under the guise of "men's health." We summarize reported testosterone:estradiol ratios, both naturally occurring and with pharmacologic manipulation and consider the ramifications of significant changes in these ratios. However, significant limitations exist in terms of steroid separation and measurement techniques, timing of samples, and lack of consistency from one assay to another, as well as definition of normative data. Limited data on the testosterone:estradiol ratio in men exists, particularly due to the scan data on concurrent estradiol values in men receiving testosterone therapy or aromatase inhibitors. Nonetheless, there seems to be a range of apparently beneficial values of the testosterone: estradiol radio at between 10 and 30, calculated as: testosterone in ng/dL/estradiol in pg/mL. Higher values appear to be associated with improved spermatogenesis and reduced bone density while lower values are associated with thyroid dysfunction. While there is growing awareness of the significance of the testosterone:estradiol ratio, and a sense of a desired range, the optimal value has not yet been determined. Further work is needed to clarify the measurement strategies and clearly-defined outcome measures related to the testosterone:estradiol ratio.