Menstrual cycle phase and hormonal contraceptive use influence circulating proforms of atrial natriuretic peptide, adrenomedullin, and the vasopressin proxy copeptin in healthy women

BACKGROUND: Cardiovascular disease is the main cause of mortality among women. However, the menstrual cycle and hormonal contraception are often overlooked in research. This study investigates whether concentrations of common cardiovascular biomarkers (natriuretic peptides, adrenomedullin, and copeptin) change during a menstrual cycle and with hormonal contraception use.

METHODS: Concentrations of cardiovascular biomarkers in 2 prospective cohorts were measured. In The Menstrual Cycle Study, blood samples were collected throughout a menstrual cycle, and in The Contraception Study, blood samples were collected from women using different contraceptive methods.

RESULTS: Blood samples from 19 women (The Menstrual Cycle study) and 638 women (The Contraception Study) were analyzed. Concentrations of mid-regional (MR)-pro-atrial natriuretic peptide (proANP) are highest during the early follicular phase (Delta %: median: 111.5 %, IQR: 100.6-115.9 %) and lowest during the mid-luteal phase (median: 88.0 %, IQR: 80.4-103.2 %) (P = .02). When compared to women with natural cycles, median concentrations of MR-proANP were reduced by 19.3 % in those using combined oral contraceptives (COC)/vaginal contraceptive ring and by 18.2 % in progestin-users. Additionally, copeptin concentrations were reduced by 11.9 % in COC/vaginal contraceptive ring-users, while MR-proadrenomedullin (proADM) concentrations were reduced by 15.4 % in COC/vaginal contraceptive ring-users and 11.5 % in progestin-users compared to non-users.

CONCLUSIONS: MR-proANP concentrations vary across the menstrual cycle with the highest concentrations during the early follicular phase. Furthermore, concentrations of MR-proANP, copeptin, and MR-proADM are affected by hormonal contraception. Our findings underscore the necessity to consider menstrual cycle phases and use of hormonal contraception in clinical assessment of premenopausal women when using cardiovascular biomarkers.