인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Combined oral contraceptives (COCs) are commonly prescribed for the prevention of pregnancy, as well as numerous other non-contraceptive health reasons. COCs act by suppressing the natural hormonal fluctuations of the menstrual cycle that result in ovulation. No studies have investigated the effects of COC use on endogenous estrogen biotransformation and the production of estrogen metabolites. This is important since imbalances in hormone biotransformation (e.g., inefficient methylation by catechol O-methyltransferases; COMT) are implicated in the initiation of breast cancer through the generation of genotoxic metabolites (i.e., estrogen quinones) and reactive oxygen species (ROS), and the depletion of vital antioxidants and metabolic cofactors. Here, we quantified the urinary levels of various estrogen precursors and metabolites in healthy young women who were using COCs containing drospirenone (DRSP) and ethinyl estradiol (EE) (n = 24) and controls (n = 25) via liquid chromatography-tandem mass spectrometry (LC‒MS/MS). In addition, we analysed several circulatory intermediates of the methylation cycle that are linked to the methylation of catechol estrogens via LC‒MS/MS. We found that free urinary estradiol (E2) and estrone (E1) were significantly lower, while 2-methoxyestrone (2-MeOE1) levels were significantly higher in COC users. Excretion of some metabolites including 16-hydroxylation pathway metabolites, glutathione conjugates, and DNA-adducts were also lower in COC users, although total hormone and metabolite excretion levels were not significantly different. Estrone metabolite ratios were higher in COC users, including 2&4-MeOE1:E1, 2&4-OHE1:E1, E1-3-sulphate: E1, and E1-3-glucuronide: E1. There was a positive correlation between 2-hydroxyestrogen and 2-methoxyestrogen levels in controls but not in COC users. In addition, the serum betaine and dimethylglycine (DMG) levels, as well as the betaine: choline ratio, were reduced in COC users, whereas the levels of choline and serine and the DMG: betaine ratio were significantly increased. DMG levels positively correlated with methoxyestrogens and methoxyestrogen: hydroxyestrogen ratios in COC users, while S-adenosylmethionine (SAM) negatively correlated with 2-MeOE2. Our data suggests that the use of EE/DRSP increases the flux of endogenous hormones into the hormone biotransformation pathway, resulting in increased conversion of estrogens (especially E1) into conjugated, catechol, and methylated estrogens but that the latter is limited by methyl-group donor availability. Interestingly, the increased oxidation of estrogens in COC users does not result in increased DNA-adduct formation.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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