# Circulating Gremlin-1 Reflects Age-Associated Metabolic Changes in Women

## TL;DR

This study shows that the protein Gremlin-1 increases with age in women and reflects general metabolic changes rather than being specifically linked to menopause.

## Contribution

The study identifies Gremlin-1 as a marker of systemic aging-related metabolic changes in women.

## Key findings

- Plasma Gremlin-1 levels are significantly higher in postmenopausal women compared to reproductive-aged women.
- Age, not menopause status, is associated with higher Gremlin-1 levels.
- Gremlin-1 shows inverse relationships with IGF-1 and HDL cholesterol, but these are largely due to aging.

## Abstract

Background: Menopause is accompanied by hormonal alterations that are closely linked to changes in body composition, insulin sensitivity, and cardiovascular risk in women. Gremlin-1 has recently been identified as an adipokine involved in metabolic and reproductive aging; however, its associations with endocrine and lipid biomarkers across the menopausal transition remain incompletely defined. Objectives: To evaluate the relationships between plasma Gremlin-1 and IGF-1, HDL cholesterol, estradiol, and age in reproductive-aged and postmenopausal women. Methods: This cross-sectional study included 88 women aged 18–65 years, stratified by menopausal status (reproductive-aged vs. postmenopausal). Plasma concentrations of Gremlin-1, growth hormone, IGF-1, insulin, estradiol (E2), glucose, HbA1c, and a standard lipid profile were measured. Results: Plasma Gremlin-1 concentrations were significantly higher in postmenopausal women compared with reproductive-aged women (p < 0.001). Age (p = 0.013), but not menopause status (p = 0.874), was associated with Gremlin-1 levels. Gremlin-1 showed a strong inverse association with IGF-1 (p = 0.003) and a negative correlation with HDL cholesterol (p = 0.03) in non-obese women; however this association disappeared after adjustment for age. Conclusion: Circulating Gremlin-1 primarily reflects chronological aging and associated endocrine–metabolic changes rather than menopausal status or adiposity per se. While unadjusted associations with metabolic biomarkers are detectable, these relationships are largely attributable to aging. Gremlin-1 may therefore serve as a marker of systemic aging-related endocrine–metabolic remodeling rather than a specific indicator of ovarian aging or adipose tissue dysfunction.