Clinical Use of Aromatase Inhibitors in Adult Males

Tan, Ronny; Guay, André T.

doi:10.1002/smrj.23

Cited by 23 publications

(8 citation statements)

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“…To the best of our knowledge, this is the first experiment analyzing the behaviour of middle‐aged animals treated with an aromatase inhibitor, which confirms clinical studies showing subtle or no effects of letrozole on brain functions in women. Furthermore, these results should be taken into account in the context of the recent efforts to establish letrozole as a treatment approach for hypogonadism in elderly men …”

Section: Discussionmentioning

confidence: 99%

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Borbélyová

Domonkos

Csongová

et al. 2017

Clin Exp Pharma Physio

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Aromatase catalyzes the conversion of testosterone to estradiol and is involved in the physiological effects of sex hormones on brain function. Animal experiments have shown that the aromatase inhibitor, letrozole, can induce anxiety in young ovariectomized females that are used as a model of aging. Whether or not these effects would be similar in intact middle-aged animals is unknown. The aim of our study was to analyze the effects of letrozole on anxiety in middle-aged rats of both sexes. Fifteen month old male and female rats were treated daily with either letrozole or vehicle for 2 weeks. The elevated plus maze was used to test anxiety-like behaviour. Sex differences were found not only in plasma concentrations of testosterone but also in the effects of letrozole treatment on plasma testosterone (P<.05). The interaction between sex and treatment was also proven in locomotor activity (P<.05) and time spent in the open arms of the elevated plus maze (P<.05). Letrozole-treated male rats spent 95% less time in the open arms of the elevated plus maze than the control rats did (P<.05) suggesting an anxiogenic effect of aromatase inhibition. This difference was not found between letrozole-treated and vehicle-treated females. In contrast to previous experiments on young animals, letrozole seems to induce anxiety in male but not in female middle-aged rats. This sex-specific effect might be related to sex differences of oestrogen and androgen signalling in aging brains. These results should be taken into account in clinical applications of letrozole, especially in men.

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Section: Discussionmentioning

confidence: 99%

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Borbélyová

Domonkos

Csongová

et al. 2017

Clin Exp Pharma Physio

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“…(Kaminetsky et al, 2013; Kim et al, 2016; Wiehle et al, 2014) The use of aromatase inhibitors also has been proposed for men with hypogonadism associated with hyperestrogenemia, including subsets of men with late-onset and obesity-associated hypogonadotropic hypogonadism. (de Boer et al, 2005; Tan et al, 2014; Zumoff et al, 2003) However, as appreciation grows of the critical metabolic roles of estrogens in men, caution may be warranted in the pursuit of such anti-estrogen based approaches to treatment of male hypogonadism. Similarly, use of selective androgen receptor modulators for treatment of hypogonadism has been proposed,(Bhattacharya et al, 2016; Thirumalai et al, 2017) but this strategy may not fully restore estradiol signaling and, therefore, fail to optimize metabolic health in hypogonadal men.…”

Section: Implications For Clinical Practicementioning

confidence: 99%

Estrogens and Body Weight Regulation in Men

Rubinow

2017

Advances in Experimental Medicine and Biology

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Our understanding of the metabolic roles of sex steroids in men has evolved substantially over recent decades. Whereas testosterone once was believed to contribute to metabolic risk in men, the importance of adequate androgen exposure for the maintenance of metabolic health has been demonstrated unequivocally. A growing body of evidence now also supports a critical role for estrogens in metabolic regulation in men. Recent data from clinical intervention studies indicate that estradiol may be a stronger determinant of adiposity than testosterone in men, and even short-term estradiol deprivation contributes to fat mass accrual. The following chapter will outline findings to date regarding the mechanisms whereby estrogens contribute to the regulation of body weight and adiposity in men. It will present emergent clinical data as well as preclinical findings that reveal mechanistic insights into estrogen-mediated regulation of body composition. Findings in both males and females will be reviewed, to draw comparisons and to highlight knowledge gaps regarding estrogen action specifically in males. Finally, the clinical relevance of estrogen exposure in men will be discussed, particularly in the context of a rising global prevalence of obesity and expanding clinical use of sex steroid-based therapies in men.

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“…In sexually mature men, AI can be used to assist with low sperm count and motility, which often contributes to infertility ( Schlegel, 2012 ; Borbelyova et al, 2017 ). In later adulthood, males often experience a slow, but steady decline in serum T, thus increasing their ratio of E2 to T, which may result in enlarged or painful breasts in men ( Tan et al, 2014 ). This can be treated with an AI to reduce the amount of androgens being converted to E2 and ultimately increase serum T concentrations that naturally decline with age ( Tan et al, 2014 ; Borbelyova et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Shay

Vieira‐Potter

Rosenfeld

2018

Front. Mol. Neurosci.

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Aromatase is the enzyme responsible for converting testosterone to estradiol. In mammals, aromatase is expressed in the testes, ovaries, brain, and other tissues. While estrogen is traditionally associated with reproduction and sexual behavior in females, our current understanding broadens this perspective to include such biological functions as metabolism and cognition. It is now well-recognized that aromatase plays a vital lifetime role in brain development and neurobehavioral function in both sexes. Thus, ongoing investigations seek to highlight potentially vital sex differences in the role of aromatase, particularly regarding its centrally mediated effects. To characterize the role of aromatase in mediating such functions, effects of aromatase inhibitor (AI) treatments on humans and animal models have been determined. Aromatase knockout (ArKO) mice that systemically lack the enzyme have also been employed. Humans possessing mutations in the gene encoding aromatase, CYP19, have also provided critical insight into how aromatase affects brain function in a possible sex-dependent manner. A better understanding of how AIs, used to treat breast cancer and other clinical conditions, may detrimentally affect neurobehavioral responses will likely promote development of future therapies to combat these effects. Herein, we will provide a critical review of the current knowledge of sex differences in aromatase regulation of various neurobehavioral functions. Although many species have been used to better understand the functions of aromatase, this review focuses on rodent models and humans. Critical gaps in our present understanding of this area will be considered, and important future research directions will be discussed.

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Clinical Use of Aromatase Inhibitors in Adult Males

Cited by 23 publications

References 100 publications

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Sex‐dependent effects of letrozole on anxiety in middle‐aged rats

Estrogens and Body Weight Regulation in Men

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

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