Natural menstrual cycle and/or oral contraception diversely affect women metabolites. Longitudinal metabolic profiling under constant experimental conditions is thereby realistic to understand such effects. Thus, we investigated volatile organic compounds (VOCs) exhalation throughout menstrual cycles in 24 young and healthy women with- and without oral contraception. Exhaled VOCs were identified and quantified in trace concentrations via high-resolution real-time mass-spectrometry, starting from a menstruation and then repeated follow-up with six intervals including the next bleeding. Repeated measurements within biologically comparable groups were employed under optimized measurement setup. We observed pronounced and substance specific changes in exhaled VOC concentrations throughout all cycles with low intra-individual variations. Certain blood-borne volatiles changed significantly during follicular and luteal phases. Most prominent changes in endogenous VOCs were observed at the ovulation phase with respect to initial menstruation. Here, the absolute median abundances of alveolar ammonia, acetone, isoprene and dimethyl sulphide changed significantly (P-value ≤ 0.005) by 18.22↓, 13.41↓, 18.02↑ and 9.40↓%, respectively. These VOCs behaved in contrast under the presence of combined oral contraception; e.g. isoprene decreased significantly by 30.25↓%. All changes returned to initial range once the second bleeding phase was repeated. Changes in exogenous benzene, isopropanol, limonene etc. and smoking related furan, acetonitrile and orally originated hydrogen sulphide were rather nonspecific and mainly exposure dependent. Our observations could apprehend a number of known/pre-investigated metabolic effects induced by monthly endocrine regulations. Potential in vivo origins (e.g. metabolic processes) of VOCs are crucial to realize such effects. Despite ubiquitous confounders, we demonstrated the true strength of volatolomics for metabolic monitoring of menstrual cycle and contraceptives. These outcomes may warrant further studies in this direction to enhance our fundamental and clinical understanding on menstrual metabolomics and endocrinology. Counter-effects of contraception can be deployed for future noninvasive assessment of birth control pills. Our findings could be translated toward metabolomics of pregnancy, menopause and post-menopausal complications via breath analysis.

译文

自然月经周期和/或口服避孕对女性代谢产物的影响不同。因此,在恒定的实验条件下进行纵向代谢分析对于理解这种影响是现实的。因此,我们调查了24名有或没有口服避孕药的年轻健康女性在整个月经周期中的挥发性有机化合物 (voc) 呼气。从月经开始,然后以六个间隔 (包括下一次出血) 重复随访,通过高分辨率实时质谱法鉴定呼出的voc并以痕量浓度对其进行定量。在优化的测量设置下,在生物学上可比较的组中进行重复测量。我们观察到在所有循环中呼出气VOC浓度的明显变化和物质特异性变化,个体内变化很小。某些血源性挥发物在卵泡期和黄体期发生了显着变化。相对于初次月经,在排卵期观察到内源性voc的最显着变化。肺泡氨、丙酮、异戊二烯和二甲基硫醚的绝对中值丰度 (p值  ≤   0.005) 分别变化18.22 ↓ 、13.41 ↓ 、18.02 ↑ 和9.40 ↓ %。这些voc在联合口服避孕药的存在下表现为相反; 例如异戊二烯显著降低了30.25 ↓ %。一旦第二次出血阶段重复,所有变化都恢复到初始范围。外源苯,异丙醇,柠檬烯等的变化以及与吸烟有关的呋喃,乙腈和口服硫化氢的变化是非特异性的,并且主要取决于暴露。我们的观察结果可能会理解每月内分泌调节引起的许多已知/预先研究的代谢作用。Voc的潜在体内起源 (例如代谢过程) 对于实现这种作用至关重要。尽管混杂因素普遍存在,但我们证明了volatolomics在代谢监测月经周期和避孕药方面的真正优势。这些结果可能需要在这个方向上进行进一步的研究,以增强我们对月经代谢组学和内分泌学的基础和临床理解。避孕的反作用可以用于将来对避孕药进行无创评估。通过呼吸分析,我们的发现可以转化为妊娠,更年期和绝经后并发症的代谢组学。

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