Menstrual cycle rhythmicity: metabolic patterns in healthy women

Abstract

The menstrual cycle is an essential life rhythm governed by interacting levels of progesterone, estradiol, follicular stimulating, and luteinizing hormones. To study metabolic changes, biofluids were collected at four timepoints in the menstrual cycle from 34 healthy, premenopausal women. Serum hormones, urinary luteinizing hormone and self-reported menstrual cycle timing were used for a 5-phase cycle classification. Plasma and urine were analyzed using LC-MS and GC-MS for metabolomics and lipidomics; serum for clinical chemistries; and plasma for B vitamins using HPLC-FLD. Of 397 metabolites and micronutrients tested, 208 were significantly (p < 0.05) changed and 71 reached the FDR 0.20 threshold showing rhythmicity in neurotransmitter precursors, glutathione metabolism, the urea cycle, 4-pyridoxic acid, and 25-OH vitamin D. In total, 39 amino acids and derivatives and 18 lipid species decreased (FDR < 0.20) in the luteal phase, possibly indicative of an anabolic state during the progesterone peak and recovery during menstruation and the follicular phase. The reduced metabolite levels observed may represent a time of vulnerability to hormone related health issues such as PMS and PMDD, in the setting of a healthy, rhythmic state. These results provide a foundation for further research on cyclic differences in nutrient-related metabolites and may form the basis of novel nutrition strategies for women.

Plasma Trimethylamine N-Oxide and Its Precursors: Population Epidemiology, Parent–Child Concordance, and Associations with Reported Dietary Intake in 11- to 12-Year-Old Children and Their Parents

“…Conversely, both betaine and l -carnitine exhibited differences between menstruating and nonmenstruating adult women. Previous work identified menstrual metabolic rhythmicity for several metabolites (e.g., acylcarnitines, amino acids) involved in key metabolic pathways and proposed that these differences reflect fluctuations in anabolic requirements in response to menstrual hormonal changes (e.g., variations in demands for β-oxidation and energy utilization) ( 63 ). Nevertheless, we had limited numbers of females reporting menstruation status and larger studies are needed to determine the effect of menstruation on TMAO concentrations.…”

Inflammatory Markers in Dysmenorrhea and Therapeutic Options

“…The first half of the menstrual cycle consists of menstruation and the follicular phase during which an increase in estrogen concentration takes place. In the second half of the cycle, in the luteal phase, the peak of progesterone secretion occurs, and then, if fertilization did not happen, approximately 3 days before the onset of menstrual bleeding, the level of progesterone decreases [8]. In women, the menstrual cycle lasts 24-35 days, on average 28 days [7].…”

Menstrual Cycle Changes in Vagally-Mediated Heart Rate Variability Are Associated with Progesterone: Evidence from Two Within-Person Studies

“…After a primary peak of P4 and a secondary peak of E2 levels, both E2 and P4 withdraw premenstrually and a new cycle begins. Longitudinal and experimental work shows that the menstrual cycle can modulate affective and behavioral outcomes (e.g., [21][22][23][24]) as well as physiological functions, like nutritional metabolism (e.g., [25,26]) and vagally-mediated HRV (e.g., [27]). Intra-individual variations in vagally-mediated HRV across the menstrual cycle with their potential implications for female daily functioning and well-being have therefore been the subject of various empirical studies.…”