绝经后不同阶段内源性雄激素与胰岛素抵抗的相关性研究

Study on relationship between endogenous androgens and insulin resistance at the different stages of postmenopause

目的探讨绝经后早期、晚期内源性雄激素水平及活性变化与胰岛素抵抗之间的相关性。方法募集2009年9月至2011年9月在复旦大学附属妇产科医院就诊的绝经后早期妇女（绝经时间≤5年）105例（绝经后早期组）、绝经后晚期妇女（绝经时间≥10年）107例（绝经后晚期组），并进一步根据体质指数（BMI）分为正常体质量者（BMI〈24kg／m^2）和超重者（BMI≥24kg／m^2）。采用全自动生化分析仪测定空腹血糖（FBG）水平；采用全自动化学发光仪测定睾酮、硫酸脱氢表雄酮（DHEA—S）、性激素结合球蛋白（SHBG）及空腹胰岛素（FINS）水平，并计算游离雄激素指数（FAI，代表雄激素活性）和稳态模型胰岛素抵抗指数（HOMA—IR）；采用偏相关分析法、多元线性回归法分析SHBG、FAI、睾酮、DHEA—S与胰岛素抵抗的相关性。结果绝经后晚期组妇女FINS[（7．9±6．6）mU／L]、HOMA—IR（2．1±1．9）高于绝经后早期组[FINS水平为（6．6±4．0）mU／L、HOMA—IR为1．7±1．1]，而绝经后晚期组DHEA—S为（0．9±0．5）mg／L，低于绝经后早期组的（1．1±0．5）mg／L，两组上述各指标间分别比较，差异均有统计学意义（P〈0．05）。两组妇女中，超重者HOMA．IR（绝经后早期组为2．2±1．0；绝经后晚期组为2．8±2．6）、FINS[绝经后早期组（6．9±2．9）mU／L；绝经后晚期组（10．2±9．3）mU／L]高于正常体质量者HOMA-IR（绝经后早期组为1．2±0．9；绝经后晚期组为1．6±1．1）、FINS[绝经后早期组（4．6±2．0）mU／L；绝经后晚期组（6．4±3．6）mU／L]，差异有统计学意义（P〈0．05）。绝经后早期组妇女中，超重者SHBG[（52±37）nmol／L]低于正常体质量者[（71±37）nmol／L]，而超重者FAI（2．5±2．1）高于正常体质量者（1．3±1．1）；在绝经后晚期组妇女中，超重者DHEA—S为（1．0±0．5）mg／L，高于正常体质量者的（0．8±0．4）m∥L，分别比较差异均有统计学意义（P〈0．05）。绝经后早期组妇女SHBG与FINS、HOMA—IR呈负相关（β值分别为-0．386、-0．553，P均〈0．05），DHEA—S与FBG呈正相关（β=0．348，P〈0．05）；绝经后晚期妇女FAI与FBG呈正相关（β=0．505，P〈0．05）。结论绝经后雄激素活性相对升高与胰岛素抵抗风险增加有关，这种相关性在绝经后不同阶段表现有所不同，主要表现为在绝经后早期SHBG与胰岛素抵抗风险增加呈负相关，DHEA—S与血糖升高风险呈正相关；在绝经后晚期，FAI与血糖升高风险呈正相关。

Objective To investigate the relationship between insulin resistance and endogenous androgens at early and late phase of postmenopause. Methods A total of 105 women with early postmenopause （≤5 years since menopause） and 107 women with late postmenopause （≥10 years since menopause） were enrolled in this study. In the mean time, those women were classified into normal weight [ body mass index （BMI）, BMI 〈 24 kg/m^2] group and overweight （BMI≥24 kg/m^2 ） group. Sex hormonebinding globulin （ SHBG）, testosterone （ T ）, dehydroepiandrosterone-sulfate （ DHEA-S ）, fasting blood glucose（ FBG）, fasting insulin （FINS）levels were measured and then calculated free androgen index（FAI） and homeostatic model assessment of insulin resistance （HOMA-IR）. The relationship between sex hormones and insulin resistance was analyzed by partial correlation and multiple linear regression analyses. Results Compared to early postmenopausal women, late postmenopausal women had higher FINS [ （7.9 ＋6. 6） mU/L versus （6. 6 ＋4. 0） mU/L] and HOMA-IR（2. 1 ±1.9 versus 1.7 ± 1.1 ）, but they had lower DHEA-S [ （0. 9 ＋ 0. 5 ） mg/L versus （ 1. l ± O. 5 ） mg/L, all P 〈 0. 05 ） ]. Both in early postmenopausal and late postmenopausal groups, overweight women had higher HOMA-IR （ early group,2. 2 ±1.0 versus 1.2 ± 0.9;late group,2. 8 ±2.6 versus 1.6 ± 1.1）and FINS early group[ （6.9 ＋2.9） mU/L versus （4.6 ＋ 2. O） mU/L] ;late group [ （ 10. 2 ＋ 9. 3） mU/L versus （6. 4 ＋ 3.6） mU/L] than those at women with normal weight group （ all P 〈 O. 05 ）. In early postmenopausal group, overweight women had lower SHBG [ （52 ± 37） nmol/L versus （71 ＋ 37 ） nmol/L]and higher FAI（ 2. 5 ± 2. 1 ） versus （ 1.3 ＋ 1.1 ） than those at normal weight women group（ all P 〈 0. 05 ）. In late postmenopausal group, overweight women had higher DHEA-S （ 1.0 ± 0. 5 ） mg/L versus （0. 8 ± O. 4） mg/L （ P 〈 O. 05 ）. The analyses suggested that in early postmenopausal group, SHBG was correlated negatively with FINS and HOMA-IR （β = - 0. 386, P 〈 0. 05 ; β = -0. 553,P 〈0. 05）, DHEA-S was correlated positively with FBG （β = 0. 348, P 〈 O. 05） in early postmenopausal group. FAI was correlated positively with FBG in late postmenopausal group （β= O. 505, P 〈 0. 05）. Conclusions The increased androgenic activities are associated with insulin resistance after of menopause. These correlations are different at different stages of postmenopause, which SHBG levels correlate with high risk of insulin resistance and DHEA-S levels correlates with high blood glucose levels at early postmenopause and FAI correlates with high blood glucose levels at late postmenopause.