Natural menstrual rhythm and oral contraception diversely affect exhaled breath compositions

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.

On-Line Analysis of Exhaled Breath

“…Several factors have been found to influence breath composition. This includes body position 24 , daytime 275 , oral/nasal breathing 276 , exhalation strength 277 , upper-airway restrictions 278 and even menstrual cycles 279 . Even when the sampling protocol is perfectly uniform, technical variability over time can add noise to the data or lead to false discoveries when the measurements are not randomly assigned.…”

Exhaled breath compositions under varying respiratory rhythms reflects ventilatory variations: translating breathomics towards respiratory medicine

“…Previously, we employed continuous VOC profiling to track minute but significant physiological fluctuations under varying respiratory flow, -exhalation kinetics, -forced expiration 15 and under increased upper-airway resistances 16 . Thus, while VOC profiling enabled us to model complex physiological and metabolic variability 17 , we realised that any normal but unsupervised physiological effects during sampling may override the actual pathophysiological impression in obtained data. This may lead us to clinical misinterpretation of results.…”

Changes of Exhaled Volatile Organic Compounds in Postoperative Patients Undergoing Analgesic Treatment: A Prospective Observational Study

“…Gut bacteria regulate the activity of ß-glucuronidase and ß-lyase enzymes [ 24 ], which reversibly control the methylation process. Administrations of non-steroidal anti-inflammatory drugs [ 25 ], morphine [ 26 ], steroids, and contraceptives [ 27 ] downregulate the natural activity of these enzymes and may cause dysbiosis of gut microbiota [ 28 ]. The decrease of volatile sulfur compounds may therefore be related to the downregulation of the methylation process by the administered analgesic therapy.…”

“…Therefore, potential biases caused by unphysiological breathing maneuvers [ 47 , 48 ], restrictions in the sampling system [ 49 ], or storage effects can be avoided. This kind of direct sampling technique was investigated in any depth [ 50 , 51 , 52 ], has been proven to be reliable, and has successfully been applied in several (clinical) studies [ 13 , 27 , 53 ]. As the patients of this study were breathing normally at respiratory rates between 10 and 18 breaths per minute, ventilation rates did not vary significantly during the measurements.…”