Changes Observed Among Lipocalin-2, Estrogen, and Osteocalcin Serum Levels in Pre and Postmenopausal Women

Introduction: Menopause is a stage in which women present physiological and metabolic changes, including visceral fat accumulation or lipid profile alterations, responsible for an increased risk of developing cardiovascular diseases, metabolic syndrome, or osteoporosis. Because adipokines, through their corresponding receptors, participate in different metabolic functions, a change in the serum concentration of these proteins is often associated with cardiometabolic impairment. Lipocalin-2 (LCN2) is an adipokine synthesized in several organs whose secretion increases when an inflammatory or infectious process occurs. Estrogen down-regulates lipocalin-2 expression within gonadal adipose tissue, while in bone tissue, this adipokine regulates energy homeostasis in osteoblasts. Considering the latter, as well as the scarce information regarding the role lipocalin-2 plays during menopause, we considered it important to measure the serum levels of lipocalin-2 in females in the pre and postmenopausal stages to assess if there is a change in lipocalin-2 serum levels between these two reproductive stages and also if there is a correlation between this change and those corresponding to other metabolic parameters. Methods: We conducted a prospective cross-sectional study of 79 healthy women, comprising 33 in the premenopausal stage and 46 in the postmenopausal stage, who were not receiving hormonal replacement therapy. To analyze all the biochemical parameters, sera from all subjects were obtained after centrifugation of 5 ml of venous blood samples drawn after an 8-12-hour fasting period. We quantified all biochemical and anthropological parameters according to previously reported methodology. We assessed the circulating levels of adipokines using competitive electro-immunoassay kits. Results: The average age of participants was 52 ± 0.7 years. The mean ± SEM for the Body Mass Index (BMI) within the two groups was 29.5 ± 0.90 kg/m2. Fasting glucose levels were within the normal range in both groups. The rest of the biochemical parameters were higher than the normal range. Osteocalcin levels were higher in postmenopausal women (6.1 ± 0.46 ng/mL) than those reported in women in the premenopausal stage (5.2 ± 0.88 ng/mL) (P ≤ 0.03). In the premenopausal group, the lipocalin-2 circulating concentration was 28 ± 3.4 ng/mL, whereas postmenopausal women presented a reduction in lipocalin-2 circulating levels (18 ± 2.7 ng/mL; P≤ 0.003). Regarding estradiol, the average value in the premenopausal group was 99 ± 18 pg/mL and 19 ± 0.23 pg/mL in the postmenopausal group (P≤ 0.0001). In addition, during post menopause, lipocalin-2 correlated positively with estrogen (r=0.35, P≤ 0.04). Discussion: We found that osteocalcin serum levels increased significantly in postmenopausal women. Moreover, in this group, data analysis showed a statistically significant positive correlation between lipocalin-2 serum concentration and estrogen levels. The latter was unexpected because we initially hypothesized an increment of lipocalin-2 levels due to a decline in estrogen. These results may not be due to a direct molecular interaction among the variables studied but rather a consequence of the metabolic state within the postmenopausal group.