Cekan S Z, Beksac M S, Wang E, Shi S, Masironi B, Landgren B M, Diczfalusy E
Contraception. 1986 Apr;33(4):327-45. doi: 10.1016/0010-7824(86)90095-8.
Twenty normally menstruating women volunteered for a study in which plasma samples were collected daily during an entire menstrual cycle. On the same days, samples of morning urine were also collected, as well as random samples of urine voided at the visit to the Outpatient Clinic. Progesterone (P), estradiol (E2) and lutropin (LH) were assayed in plasma, and pregnanediol-3-glucuronide (PdG), estrone-glucuronide (E1G), estriol-16-glucuronide (E3G), P, and E2 were measured in urine using radioimmunoassays. Progesterone in urine was assayed both with and without preceding chromatography. All urinary glucuronides and progesterone exhibited cyclic patterns similar to those of E2 or P in plasma. Seven-fold increases from early follicular to luteal phase values (for PdG and urinary P; the latter both with and without chromatography), or to peak levels (for E1G and E3G) were observed. The difference between the baseline and peak levels was less distinct (approximately 5-fold) for E2 in urine. The day-to-day coefficient of variation of early follicular phase values decreased from 40% to 25% by calculating the ratios of the glucuronides or P to creatinine (C). The peaks of estrogen glucuronides were delayed mostly by 1 day in comparison to the peaks of E2 in plasma. The urinary peaks of estrogens were in most cases more closely clustered around the day of the LH-peak when the measurements were corrected for C. For the determination of the first significant rise of steroid levels in a cycle, the calculation of a sustained rise (leading to a significant cumulative sum - CUSUM) was found superior when compared to other recommended indices, such as a 50% increase over the mean of 3 preceding values, or the increase over the baseline level plus 2 standard deviations. Sustained rises were calculated for all indices studied (including the ratio of urinary E1G to PdG). The ratio of E1G to C in morning urine gave consistently the most compact distribution of sustained rises. It is concluded that daily measurements of urinary PdG (or P) and E1G (or, possibly, E2) could substitute the serial assays of P and E2 in peripheral blood in the retrospective assessment of the ovarian functionn. The day-to-day variation can be significantly reduced, if results are expressed per concentration of C. For the prediction of ovulation or fertile period, the best index of urinary steroids appears to be the sustained rise in the ratio of E1G to C. However, this "best" method is still not good enough in terms of overall reliability and practicability.
20名月经周期正常的女性自愿参与一项研究，在整个月经周期中每天采集血浆样本。在同一天，还采集晨尿样本以及门诊就诊时随机排出的尿液样本。采用放射免疫分析法测定血浆中的孕酮（P）、雌二醇（E2）和促黄体生成素（LH），并测定尿液中的孕二醇 - 3 - 葡萄糖醛酸苷（PdG）、雌酮 - 葡萄糖醛酸苷（E1G）、雌三醇 - 16 - 葡萄糖醛酸苷（E3G）、P和E2。尿液中的孕酮在进行色谱分析前后均进行测定。所有尿液中的葡萄糖醛酸苷和孕酮均呈现出与血浆中E2或P相似的周期性模式。观察到从卵泡早期到黄体期的值（对于PdG和尿液中的P，后者进行色谱分析前后）增加了7倍，或达到峰值水平（对于E1G和E3G）。尿液中E2的基线水平与峰值水平之间的差异较小（约5倍）。通过计算葡萄糖醛酸苷或P与肌酐（C）的比值，卵泡早期值的每日变异系数从40%降至25%。与血浆中E2的峰值相比，雌激素葡萄糖醛酸苷的峰值大多延迟1天。当测量值校正C后，雌激素的尿液峰值在大多数情况下更紧密地聚集在LH峰值日周围。对于确定一个周期中类固醇水平的首次显著升高，与其他推荐指标（如比前三个值的平均值增加50%，或比基线水平增加加上2个标准差）相比，计算持续升高（导致显著的累积和 - CUSUM）被发现更优越。对所有研究的指标（包括尿液中E1G与PdG的比值）都计算了持续升高。晨尿中E1G与C的比值始终给出最紧凑的持续升高分布。得出结论，在回顾性评估卵巢功能时，每日测定尿液中的PdG（或P）和E1G（或可能的E2）可以替代外周血中P和E2的系列测定。如果按C的浓度表示结果，每日变异可以显著降低。对于预测排卵或排卵期，尿液类固醇的最佳指标似乎是E1G与C比值的持续升高。然而，就总体可靠性和实用性而言，这种“最佳”方法仍不够好。
