Breath Volatile Organic Compounds Across the Menstrual Cycle: A Pilot Study Using PTR-TOF–MS

Background Accurate identification of ovulation remains challenging due to pronounced inter- and intra-individual variability of reproductive hormones. Volatile organic compounds (VOCs) in exhaled breath may vary across the menstrual cycle and offer a non-invasive complementary approach to menstrual cycle assessment. Methods In this pilot study, exhaled breath VOCs were measured using proton transfer reaction time-of-flight mass spectrometry in five healthy women across follicular, ovulatory, and luteal phases of a natural menstrual cycle. The VOC profiles were compared between ovulatory and non-ovulatory measurements, and correlations with serum hormone concentrations of estradiol (E2), luteinizing hormone (LH), and progesterone (P) were explored. Results A significant difference between ovulatory and non-ovulatory measurements was observed for the ion m/z 41.04 (p = 0.021). Non-significant trends toward higher concentrations during ovulation were detected for isoprene-related signals. Conclusion Breath VOCs exhibit phase-dependent alterations across the menstrual cycle. The observed increase in the m/z 41.04 signal during ovulation may reflect integrated metabolic adaptations associated with endocrine changes rather than direct surrogates of circulating hormone concentrations.