CNN-Dma

Variation in the UGT2B17 genotype, exemestane metabolism and menopause-related toxicities in the CCTG MAP.3 trial

“…The UGT2B17 gene deletion can lead to increased circulating androgen concentrations that in turn can lead to increased estrogen production through aromatase activity. Several studies have observed higher bone mineral density (marker of increased estrogen exposure) in postmenopausal women with the homozygous UGT2B17 gene deletion compared to women with one or both alleles of the UGT2B17 gene [12][13], and when restricted to women not taking HT [11]. However, to our knowledge, the impact of the UGT2B17 gene deletion on non-bone related menopause symptoms has not been previously described.…”

“…Paradoxically, in the absence of aromatase inhibitors, the UGT2B17 homozygous gene deletion is associated with altered sex steroid metabolism [4,8,10]. Emerging evidence in postmenopausal women has suggested that increasing androgen concentrations may also result in increased estrogen production through aromatase activity, which is of particular importance due to already-low estrogen levels in these women [11][12][13].…”