Fluctuations in Metabolites and Bone Markers Across the Menstrual Cycle in Eumenorrheic Women and Oral Contraceptive Users

Abstract

Context: Little is known about changes in circulating metabolites during the menstrual cycle and how use of oral contraceptives (OCs) affects these changes.

Objectives: To study fluctuations in circulating metabolite and bone marker levels during the menstrual/pill cycle in eumenorrheic women and OC users.

Methods: Plasma samples were collected from 28 eumenorrheic women and 10 OC users at 7 to 9 time points across a menstrual/pill cycle. Longitudinal and cross-sectional analyses were performed to examine the cycle- and OC-induced variations in the plasma metabolite and bone turnover marker levels.

Results: In eumenorrheic women, plasma levels of alanine, glutamine, threonine, and tyrosine varied significantly across the menstrual cycle, and all dropped to the lowest level around day 21 of the menstrual cycle. These amino acid concentrations were negatively correlated with fluctuations in progesterone and/or estrogen levels. A between-group analysis showed that plasma levels of alanine, glutamine, glycine, proline, and tyrosine were lower in OC users than in nonusers. Concomitantly, plasma C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (PINP) levels were lower in OC users. Intriguingly, when all data were pooled, variations in CTX and PINP levels were positively correlated with fluctuations in proline and glycine concentrations (r > 0.5 or 0.3 < r < 0.5, P < 0.05).

Conclusions: The menstrual cycle and the use of OCs alter plasma levels of metabolites and bone turnover markers in young women. While the impact of these findings remains to be established, the lower glycine level among OC users and the accompanying lower CTX level supports that the use of OCs lowers collagen turnover in young women and may thereby have long-term implications for bone health among OC users.

Trial registration: ClinicalTrials.gov NCT03832972.

Keywords: CTX; NMR metabolomics; PINP; collagen markers; hormonal contraception; plasma amino acid variations.