Davis Susan R, Turcu Adina F, Robinson Penelope J, Bell Robin J
Women's Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
University of Michigan, Ann Arbor, Michigan.
J Endocr Soc. 2019 Feb 4;3(3):670-677. doi: 10.1210/js.2018-00412. eCollection 2019 Mar 1.
11-Hydroxyandrostenedione (11OHA4), 11-hydroxytestosterone (11OHT), and their respective peripheral derivatives, 11-ketoandrostenedione (11KA4) and 11-ketotesosterone (11KT), have been implicated in androgen-related physiopathology. Little is known of these steroids in postmenopausal women or whether exogenous testosterone therapy influences their levels.
The impact of exogenous testosterone on serum levels of 11-oxygenated steroids was determined in healthy postmenopausal women.
Levels of 19-carbon (C19) steroids were measured by liquid chromatography-tandem mass spectrometry in serum obtained at baseline and at 12 and 26 weeks from 73 healthy postmenopausal women, aged 55 to 65 years, who participated in a randomized, double-blind, placebo-controlled clinical trial assessing the effects of transdermal testosterone on cognitive performance.
Of the 11-oxygenated androgens, 11OHA4 was the most abundant (median, 6.46 nmol/L; range, 1.51 to 23.82 nmol/L), with concentrations several fold greater than its precursor androstenedione (median, 1.38 nmol/L; range, 0.52 to 2.92 nmol/L). Baseline median (range) testosterone and 11KT levels were similar [0.56 (0.23 to 1.48) nmol/L; 0.85 (0.25 to 2.86) nmol/L, respectively). 11OHT was closely correlated with 11KT (Spearman rank correlation coefficient, 0.79; < 0.001) and 11OHA4 correlated with 11KA4 (Spearman rank correlation coefficient, 0.73; < 0.001). Testosterone therapy resulted in an increase in serum testosterone level, whereas all 11-oxygenated androgens remained unchanged throughout the 26 weeks of treatment.
After menopause, the adrenal production of 11-oxygenated derivatives of androstenedione and testosterone contributes importantly to the total circulating androgen pool. Exogenous testosterone does not influence the circulating levels 11-oxygenated C19 steroids.
11-羟雄烯二酮(11OHA4)、11-羟基睾酮(11OHT)及其各自的外周衍生物11-氧代雄烯二酮(11KA4)和11-氧代睾酮(11KT)与雄激素相关的病理生理学有关。对于绝经后女性体内的这些类固醇,以及外源性睾酮治疗是否会影响其水平,人们了解甚少。
确定外源性睾酮对健康绝经后女性血清中11-氧化类固醇水平的影响。
通过液相色谱-串联质谱法测量了73名年龄在55至65岁之间的健康绝经后女性在基线时以及第12周和第26周采集的血清中19碳(C19)类固醇的水平。这些女性参与了一项评估经皮睾酮对认知功能影响的随机、双盲、安慰剂对照临床试验。
在11-氧化雄激素中,11OHA4含量最为丰富(中位数为6.46 nmol/L;范围为1.51至23.82 nmol/L),其浓度比其前体雄烯二酮(中位数为1.38 nmol/L;范围为0.52至2.92 nmol/L)高出数倍。基线时睾酮和11KT的中位数(范围)相似[分别为0.56(0.23至1.48)nmol/L;0.85(0.25至2.86)nmol/L]。11OHT与11KT密切相关(斯皮尔曼等级相关系数为0.79;P<0.001),11OHA4与11KA4相关(斯皮尔曼等级相关系数为0.73;P<0.001)。睾酮治疗导致血清睾酮水平升高,而在整个26周的治疗过程中,所有11-氧化雄激素均保持不变。
绝经后,肾上腺产生的雄烯二酮和睾酮的11-氧化衍生物对总循环雄激素池有重要贡献。外源性睾酮不会影响循环中的11-氧化C19类固醇水平。