Aromatase inhibitors and mood disturbances

Rocha-Cadman, Xiomara; Massie, Mary Jane; Hamel, Katherine Du

doi:10.1017/s1478951512000636

Cited by 25 publications

(13 citation statements)

References 10 publications

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“…However, the length of life of the SERM-treated women is about the same as that of AI-treated women (5). At this point, the regimens remain unsettled (146), and concerns have been raised regarding cardiovascular complications of AIs (8,164) and mood disturbances (116). Since decreased estrogen has been implicated in cardiovascular disease and depression, the marked effect of AIs compared with partial agonist SERMs is in keeping with present knowledge (see above).…”

Section: Aromatase Inhibitorsmentioning

confidence: 64%

Aromatase: Contributions to Physiology and Disease in Women and Men

2016

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Aromatase (estrogen synthetase; EC 1.14.14.1) catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. Aromatase is most widely known for its roles in reproduction and reproductive system diseases, and as a target for inhibitor therapy in estrogen-sensitive diseases including cancer, endometriosis, and leiomyoma (141, 143). However, all tissues contain estrogen receptor-expressing cells, the majority of genes have a complete or partial estrogen response element that regulates their expression (61), and there are plentiful nonreceptor effects of estrogens (79); therefore, the effect of aromatase through the provision of estrogen is almost universal in terms of health and disease. This review will provide a brief but comprehensive overview of the enzyme, its role in steroidogenesis, the problems that arise with its functional mutations and mishaps, the roles in human physiology of aromatase and its product estrogens, its current clinical roles, and the effects of aromatase inhibitors. While much of the story is that of the consequences of the formation of its product estrogens, we also will address alternative enzymatic roles of aromatase as a demethylase or nonenzymatic actions of this versatile molecule. Although this short review is meant to be thorough, it is by no means exhaustive; rather, it is meant to reflect the cutting-edge, exciting properties and possibilities of this ancient enzyme and its products.

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Section: Aromatase Inhibitorsmentioning

confidence: 64%

Aromatase: Contributions to Physiology and Disease in Women and Men

2016

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“…Aromatase is crucial in mediating the effects of testosterone on the hippocampus, amygdala, and cortex . This specific role was used as the rationale for the small studies and case reports that demonstrated that treatment with letrozole has negative effects on cognitive and affective functions . A systematic review of relevant studies with sufficient power, on the other hand, revealed no major cognitive alternations due to aromatase inhibition .…”

Section: Introductionmentioning

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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“…A meta-analyses of 911 breast cancer patients treated with various AI treatments or TAM compared to control women further revealed that those treated with AI or TAM showed similar verbal learning and memory impairments ( 146 ). Treatment of breast cancer patients with the AI, An, has also been associated with memory deficiencies, especially in verbal memory, mood disturbances, somnolence, anxiety, fatigue, and hot flashes in some studies ( 14 , 147 – 149 ).…”

Section: Human Aromatase Studiesmentioning

confidence: 99%

Cognitive Effects of Aromatase and Possible Role in Memory Disorders

2018

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Diverse cognitive functions in many vertebrate species are influenced by local conversion of androgens to 17β-estradiol (E2) by aromatase. This enzyme is highly expressed in various brain regions across species, with some inter-species variation in terms of regional brain expression. Since women with breast cancer and men and women with other disorders are often treated with aromatase inhibitors (AI), these populations might be especially vulnerable to cognitive deficits due to low neuroE2 synthesis, i.e., synthesis of E2 directly within the brain. Animal models have been useful in deciphering aromatase effects on cognitive functions. Consequences of AI administration at various life cycle stages have been assessed on auditory, song processing, and spatial memory in birds and various aspects of cognition in rodent models. Additionally, cognitive deficits have been described in aromatase knockout (ArKO) mice that systemically lack this gene throughout their lifespan. This review will consider evidence to date that AI treatment in male and female rodent models, birds, and humans results in cognitive impairments. How brain aromatase regulates cognitive function throughout the lifespan, and gaps in current knowledge will be considered, along with future directions to better define how aromatase might guide learning and memory from early development through the geriatric period. Better understanding the importance of E2 synthesis on neurobehavioral responses at various ages will likely aid in the discovery of therapeutic strategies to prevent potential cognitive deficits, including Alzheimer's Disease, in individuals treated with AI or those possessing CYP19 gene polymorphisms, as well as cognitive effects of normal aging that may be related to changes in brain aromatase activity.

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Aromatase inhibitors and mood disturbances

Cited by 25 publications

References 10 publications

Aromatase: Contributions to Physiology and Disease in Women and Men

Aromatase: Contributions to Physiology and Disease in Women and Men

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

Cognitive Effects of Aromatase and Possible Role in Memory Disorders

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