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Background:Estradiol (E2) has been shown to exert beneficial effects on males, particularly for metabolic outcomes. However, these benefits tend to be more evident when accompanied by concurrent increase in testosterone (T) levels, when the increase of E2 is secondary to the increase of T. Oppositely to its benefits in healthy males, when under metabolic and inflammatory diseases, E2 has been reported to be a marker of worse prognosis, once E2 is unproportionally high compared to testosterone in pathological conditions, which results in hypogonadism. The collective analysis of T and E2 shows that the balance between these two hormones determines whether increase in E2 levels is physiological or pathological, demonstrated by balanced T and E2, i.e., intact T:E2 ratio compared to healthy males, and disrupted balance between T and E2, with impaired T:E2 ratio, respectivey. Hence, it seems that the dual relationship between E2 and health markers in males is based on the balance, or ratio, between T and E2. The objective of the present study is to propose a ratio between T and E2(testosterone-to-estradiol ratio, or T:E ratio) as a better predictor of health outcomes than testosterone or estradiol alone, and to differentiate health from pathological states within this single marker, from a review of the literature. Methods:We systematically searched for articles using the following criteria: 1. Any of the combinations of the expressions “testosterone” (AND) ”estradiol” (AND) “male(s)” (OR) ”men” (OR) “masculine”, or “testosterone-to-estradiol” (OR) “testosterone:estradiol” (OR) “estradiol-to-testosterone ratio” (OR) “estradiol:testosterone” (AND) “male(s)” (OR) ”men” (OR) “masculine”, to be present in the title and/or abstract; 2. Fully written in English; 3. Performed in humans; 4. Throughout the literature until Jan 30th 202020; and 5. Original researches.Results:We selected 39 articles, from which 27 were performed in healthy males, and 11 under metabolic or inflammatory conditions. Benefits of E2 in healthy males occurred irrespective of T for bone mass and quality, and anger levels. Benefits that were better identified when E2 and T were evaluated together include better libido, improved cognitive functions, improved well-being and other mood states, increased muscle mass, enhanced loss of fat mass, quality, increased basal metabolic rate, increased fat oxidation, and reduced cardiovascular markers, including reduced maximal intimal-media carotids thickness, when T:E ratio was > 13.7. In pathological states, increased estradiol was associated to increased risk of disease-specific complications, and worse quality of life, particularly when T:E was < 9.5. T:E ratio was also able to accurately identify healthy athletes from those affected by any sport-related metabolic conditions.Conclusion:Testosterone-to-estradiol (T:E) ratio is likely a more precise predictor of metabolic-related health outcomes in both healthy and pathological states, compared to testosterone or estradiol alone.

journal of the endocrine society

SAT-LB8 The Testosterone-To-Estradiol Ratio, Rather Than Testosterone or Estradiol Alone, Is a More Precise Marker of Metabolic-Related Outcomes in Males: Insights From a Systematic Review