Department of Obstetrics and Gynaecology, University Hospital of Oulu, PL 23 90029 OYS, Oulu, Finland.
Hum Reprod. 2012 Nov;27(11):3279-86. doi: 10.1093/humrep/des309. Epub 2012 Aug 29.
Are self-reported menstrual disorders associated with hyperandrogenaemia and metabolic disturbances as early as in adolescence?
Menstrual disorders at the age 16 are a good marker of hyperandrogenaemia, and an adverse lipid profile was associated with higher androgen levels.
Hyperandrogenism per se has been suggested to be a significant metabolic risk factor in women and a cause of physical and psychological morbidity in adolescent girls. A weak positive correlation has been described between hyperandrogenaemia and obesity in adolescent girls, but the clinical consequences are still poorly understood. Hyperandrogenism and insulin resistance are also key features of polycystic ovary syndrome (PCOS), and women with PCOS are consequently at an increased risk of developing type 2 diabetes mellitus and/or metabolic syndrome, and may have increased cardiovascular morbidity. Our findings confirm that the association between menstrual disorders, hyperandrogenism, obesity and metabolic risks is already evident in adolescence.
This population-based, cross-sectional study used postal questionnaires to targeting 15-16-year-old girls in the Northern Finland Birth Cohort 1986 (n= 4567).
There were 3669 girls who answered the postal questionnaire and out of 3373 girls who also underwent clinical examinations and blood tests, 2448 were included in the analyses. The questionnaire included one question about the regularity and length of the menstrual cycle: 'Is your menstrual cycle (the interval from the beginning of one menstrual period to the beginning of the next period) often (more than twice a year) longer than 35 days?' The girls who answered 'yes' to this question were considered to be suffering from menstrual disorders and were classified as 'symptomatic'. The girls who answered 'no' were defined as 'non-symptomatic'.
There were 709 (29%) girls who reported menstrual disorders (symptomatic girls) and 1739 who had regular periods (non-symptomatic girls). In the whole population and in both study groups, there were significant correlations between body mass index (BMI) (and waist-to-hip ratio), hyperandrogenaemia and metabolic parameters. Symptomatic girls exhibited significantly higher serum concentrations of testosterone (P= 0.010), lower levels of sex hormone-binding globulin (P =0.042) and higher free androgen indices [FAIs; geometric mean 3.38 (interquartile range (IQR): 2.27, 5.18) versus 3.08 (IQR: 2.15, 4.74), P= 0.002]. The two groups had comparable BMI and insulin sensitivity, and serum levels of glucose, insulin and lipids. There was a significant linear trend towards higher FAI values in the higher BMI quartiles in both symptomatic and non-symptomatic girls. In the whole population, there was a statistically significant linear decrease in high-density lipoprotein concentrations (P < 0.001) and higher triglyceride concentrations (P =0.004) in the upper FAI quartile.
Information regarding menstrual disorders in adolescence is a good marker of hyperandrogenaemia and may be an early risk factor for the development of PCOS in adulthood. The association between obesity, hyperandrogenism and metabolic risks is already evident in adolescence, which strengthens the importance of noting menstrual disorders at an early stage. BIAS, LIMITATIONS, GENERALIZABILITY: The cross-sectional nature of the study does not allow us to draw conclusions concerning the metabolic risks of this population in later life. The diagnosis of menstrual disorders was based on a questionnaire, suggesting a risk of information bias in reporting the symptoms. This study was not designed to diagnose PCOS, as ultrasonography was not available and there was no clinical evaluation of hyperandrogenism (i.e. hirsutism). However, we were able to take into account potential confounding factors in the analyses.
STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the Finnish Medical Society Duodecim, the North Ostrobothnia Regional Fund, the Academy of Finland (project grants 104781, 120315, 129269, 1114194, SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643) and the Medical Research Council, UK (PrevMetSyn/SALVE). None of the authors have any conflict of interest to declare.
青春期少女的自我报告的月经紊乱是否与高雄激素血症和代谢紊乱有关？
16 岁时的月经紊乱是高雄激素血症的良好标志物，而不良的血脂谱与更高的雄激素水平相关。
雄激素过多症本身已被认为是女性的重要代谢危险因素，也是青春期少女身体和心理发病的原因。已经描述了青春期少女中高雄激素血症与肥胖之间存在弱正相关，但临床后果仍知之甚少。高雄激素血症和胰岛素抵抗也是多囊卵巢综合征（PCOS）的关键特征，因此患有 PCOS 的女性发生 2 型糖尿病和/或代谢综合征的风险增加，并且可能心血管发病率增加。我们的研究结果证实，青春期少女中月经紊乱、高雄激素血症、肥胖和代谢风险之间的关联已经很明显。
这是一项基于人群的横断面研究，使用邮寄问卷针对 1986 年芬兰北部出生队列的 15-16 岁女孩（n=4567）。
有 3669 名女孩回答了邮寄问卷，在 3373 名接受临床检查和血液检查的女孩中，有 2448 名女孩纳入了分析。问卷中包含一个关于月经周期规律性和长度的问题：“您的月经周期（从一次月经开始到下一次月经开始的间隔）是否经常（超过两年一次）长于 35 天？”回答“是”的女孩被认为患有月经紊乱，并被归类为“症状性”。回答“否”的女孩被定义为“非症状性”。
有 709 名（29%）女孩报告了月经紊乱（症状性女孩），1739 名女孩月经规律（非症状性女孩）。在整个人群和两个研究组中，体重指数（BMI）（和腰臀比）、高雄激素血症和代谢参数之间都存在显著相关性。症状性女孩的血清睾酮浓度显著升高（P=0.010），性激素结合球蛋白水平降低（P=0.042），游离雄激素指数升高[FAI；几何平均值 3.38（四分位距（IQR）：2.27，5.18）与 3.08（IQR：2.15，4.74），P=0.002]。两组的 BMI 和胰岛素敏感性以及血清葡萄糖、胰岛素和脂质水平相当。在症状性和非症状性女孩中，BMI 四分位数越高，FAI 值呈显著线性升高趋势。在整个人群中，高密度脂蛋白浓度呈统计学显著下降（P<0.001），FAI 四分位数越高，甘油三酯浓度越高（P=0.004）。
青春期少女的月经紊乱信息是高雄激素血症的良好标志物，可能是成年后患 PCOS 的早期危险因素。肥胖、高雄激素血症和代谢风险之间的关联在青春期已经很明显，这加强了早期注意月经紊乱的重要性。
偏倚、局限性、普遍性：研究的横断面性质不允许我们得出关于该人群以后生活中的代谢风险的结论。月经紊乱的诊断基于问卷调查，因此在报告症状时存在信息偏倚的风险。本研究的目的不是诊断 PCOS，因为没有进行超声检查，也没有对高雄激素血症（即多毛症）进行临床评估。然而，我们能够在分析中考虑到潜在的混杂因素。
研究资金/利益冲突：这项工作得到了芬兰医学协会 Duodecim、北奥斯特罗波西亚地区基金、芬兰科学院（项目资助 104781、120315、129269、1114194、SALVE）、奥卢大学医院、生物中心、奥卢大学、芬兰（75617）、欧洲委员会（欧盟-BLCS，框架 5 奖 QLG1-CT-2000-01643）和英国医学研究委员会的支持。作者均无任何利益冲突。
