Abstract
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.
Highlights
The natural endocrine regulation in young and healthy adult women during their menstrual cycle is an everlasting clinical interest[1,2]
What are the effects of natural menstrual cycle onto exhaled breath volatile organic compounds (VOCs) concentrations in young and healthy women?
Observed changes in endogenous and blood-borne VOCs were assignable to the ovulation phase in the cohort without contraception
Summary
The natural endocrine regulation in young and healthy adult women during their menstrual cycle is an everlasting clinical interest[1,2]. Real-time mass-spectrometric (MS) techniques e.g. proton transfer reaction (PTR)-Time of flight (ToF)-MS30,31 along with end-tidal/alveolar sampling[32,33] have enabled online monitoring of immediate physiological changes within split-seconds[34,35,36]. These studies showed that concentration changes may be more important than the presence of unique breath VOC biomarkers. We follow-up changes in exhaled VOC concentrations from young and healthy women during their normal menstrual cycles and throughout the cycles undergoing combined oral contraception by applying high-resolution PTR-ToF-MS. What are the effects of natural menstrual cycle onto exhaled breath VOC concentrations in young and healthy women?
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