MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone

Abstract

Evidence has been accumulating that, in men, some of the biological actions traditionally attributed to testosterone acting via the androgen receptor may in fact be dependent on its aromatization to estradiol (E2). In men, E2 circulates at concentrations exceeding those of postmenopausal women, and estrogen receptors are expressed in many male reproductive and somatic tissues. Human studies contributing evidence for the role of E2 in men comprise rare case reports of men lacking aromatase or a functional estrogen receptor alpha, short-term experiments manipulating sex steroid milieu in healthy men, men with organic hypogonadism or men with prostate cancer treated with androgen deprivation therapy (ADT) and from observational studies in community-dwelling men. The collective evidence suggests that, in men, E2 is an important hormone for hypothalamic–pituitary–testicular axis regulation, reproductive function, growth hormone insulin-like growth factor-1 axis regulation, bone growth and maintenance of skeletal health, body composition and glucose metabolism and vasomotor stability. In other tissues, particularly brain, elucidation of the clinical relevance of E2 actions requires further research. From a clinical perspective, the current evidence supports the use of testosterone as the treatment of choice in male hypogonadism, rather than aromatase inhibitors (which raise testosterone and lower E2), selective androgen receptor modulators and selective estrogen receptor modulators (with insufficiently understood tissue-specific estrogenic effects). Finally, E2 treatment, either as add-back to conventional ADT or as sole mode of ADT could be a useful strategy for men with prostate cancer.

Inter-correlations Among Clinical, Metabolic, and Biochemical Parameters and Their Predictive Value in Healthy and Overtrained Male Athletes: The EROS-CORRELATIONS Study

“…Hence, the balance between testosterone and estradiol might be more important than either testosterone or estradiol alone. This is extensively supported by the literature, since the T:E ratio predicts multiple outcomes, including cardiovascular changes (29,30), while many of the neuroprotective and psychological effects of estradiol in males are mediated by testosterone (32)(33)(34), which requires a balance between these hormones to obtain the health benefits. The unaltered balance is more precisely assessed by the T:E ratio, rather than each hormone alone.…”

“…Although estradiol alone did not predict body metabolism or composition parameters, it independently predicted lower anger. Although estradiol receptors are widely distributed in the brain (29,33,34), their effects on mood in males are still unclear. Body water content was the only predictor of fat oxidation, which supports the premise that good hydration status, particularly within the cells, is a key requirement for proper fat oxidation, as water is part of this pathway (35)(36)(37), while dehydration slightly impaired fat burning.…”

“…Level of hydration is a key characteristic for the overall health status in humans, since water is a major participant of multiple reactions of metabolism and thermoregulation (37). Hydration, measured by the % of body water in relation to total body weight, was associated with multiple parameters (20,22,34), including both characteristics of body metabolism(the predictedto-measured BMR ratio and fat oxidation), which is reasonable since water boosts fat metabolism (35,36,93,94,96) and overall metabolic rate (35,94,(96)(97)(98)(99), being considered as a potential thermogenic (35,36,93,94,(96)(97)(98).…”

Late‐onset hypogonadism: metabolic impact

“…Observational evidence associating circulating estradiol with diabesity is however scant and contradictory, in part because of the collinearity of circulating testosterone (the substrate) with estradiol (the product). Further, estradiol was measured by immunoassay in the majority of studies, which lacks accuracy in quantifying the relatively low circulating estradiol concentrations in men (Russell & Grossmann, 2019).…”

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

“…Androgen deprivation therapy, which is achieved by medical or surgical castration as well as by estrogen therapy, has been widely used in the treatment of prostate cancer for many decades [19]. Moreover, male-to-female transsexual patients use estrogen therapy to adapt their physical bodies to those of the female sex [20,21]. Though estrogen therapy can induce gynecomastia in men, its transdermal or parenteral route of administration was reported to reduce the risk of toxicity [22,23].…”