Effect of Menstrual Cycle and Menopause on Human Gastric Electrophysiology

Abstract

Chronic gastroduodenal symptoms disproportionately affect females of childbearing age; however, the effect of menstrual cycling on gastric electrophysiology is poorly defined. To establish the effect of the menstrual cycle on gastric electrophysiology, healthy subjects underwent non-invasive Body Surface Gastric Mapping (BSGM; 8x8 array), with validated symptom logging App (Gastric Alimetry, New Zealand). Participants were premenopausal females in follicular (n=26) and luteal phases (n=18). Postmenopausal females (n=30) and males (n=51) were controls. Principal gastric frequency (PGF), BMI-adjusted amplitude, Gastric Alimetry Rhythm Index (GA-RI), fasted-fed amplitude ratio (ff-AR), meal response curves, and symptom burden were analysed. Menstrual cycle-related electrophysiological changes were then transferred to an established anatomically-accurate computational gastric fluid dynamics model (meal viscosity 0.1 Pas), to predict the impact on gastric mixing and emptying. PGF was significantly higher in the luteal vs. follicular phase (mean 3.21 cpm, SD (0.17) vs. 2.94 cpm, SD (0.17), p<0.001) and vs. males (3.01 cpm, SD (0.2), p<0.001). In the computational model, this translated to 8.1% higher gastric mixing strength and 5.3% faster gastric emptying for luteal versus follicular phases. Postmenopausal females also exhibited higher PGF than females in the follicular phase (3.10 cpm, SD (0.24) vs. 2.94 cpm, SD (0.17), p=0.01), and higher BMI-adjusted amplitude (40.7 uV (33.02-52.58) vs. 29.6 uV (26.15-39.65), p<0.001), GA-RI (0.60 (0.48-0.73) vs. 0.43 (0.30-0.60), p=0.005), and ff-AR (2.51 (1.79-3.47) vs. 1.48 (1.21-2.17), p=0.001) than males. There were no differences in symptoms. These results define variations in gastric electrophysiology with regard to human menstrual cycling and menopause.

Nausea and Gastric Myoelectrical Activity are Influenced by Hormonal Contraception in Chronic Gastroduodenal Disorders

“…The most notable change was in Principal Gastric Frequency, which was elevated with exogenous hormone delivery, particularly in formulations containing significant quantities of progestogen. This finding is consistent with a separate study recently performed by our group, which showed that similar elevations in gastric frequency occur normally during the luteal phase of the menstrual cycle in women not taking hormonal contraception when circulating progesterone is also elevated (38). Taken together, these data likely explain why females exhibit higher overall gastric frequencies than males in normative range datasets (25).…”

“…While our study did not specifically address causality, a causal link can be reasonably postulated between hormonal contraception and nausea due to consistent and coherent evidence across adjacent literature, including temporal and dose-response relationships, as well as biological plausibility (35,36). For example, nausea and vomiting are commonly observed during fluctuations or surges in female sex hormones, as seen in menstrual cycling (18,37,38), pregnancy (39,40), as a side-effect of initiating hormonal contraception in healthy women (41,42); (43–46), and following the administration of emergency contraceptives (43–46). Symptoms have also been noted to fluctuate across the menstrual cycle in patients with gastroparesis, being heightened in the luteal phase (18).…”

“…While the changes in gastric frequency related to contraception use may appear modest, it should be noted that physiological homeostasis maintains PGF in a very tight range (2.65-3.35 cycles per minute) and thus a difference of 0.1 cpm, particularly after adjustment for age and multiple comparisons, reflects a relevant difference between the groups. It should be noted that the median PGF for all groups remained within a normal range (25), and the differences themselves are therefore unlikely to directly induce gastroduodenal symptoms; however, they may lead to small physiological increases in gastric mixing and emptying (38). In addition, while gastric dysrhythmias have previously been associated with both exogenous female sex hormone administration and nausea (20), dysrhythmias were not observed to be specifically associated with hormonal contraception use in our current study, as measured by the validated ‘Rhythm Index’ metric by the Gastric Alimetry System (see Supplementary Figure 1 ) (26).…”

Short‐ and long‐term reproducibility of body surface gastric mapping using the Gastric Alimetry® system

“…However, research has shown no significant differences in the results of EGG 56 or BSGM 57 for calorie‐matched meals with different compositions. In addition, we did not account for menstrual cycle variability in premenopausal female subjects, with elevations in Principal Gastric Frequency recently shown to occur during the luteal phase 58 . Future research is needed to investigate the effect of the menstrual cycle on the reproducibility of the Gastric Alimetry metrics.…”