Hormone replacement therapy (HRT) reduces the risk for osteoporosis but transiently increases cardiovascular risk for some postmenopausal women. This study investigated the hypothesis that these risks are associated with HRT-induced changes in mononuclear cell secretion of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and associated soluble receptors. Compared to the untreated condition (n=8), estrogen therapy (n=7) and estrogen+progestin therapy (n=7) both caused 2-fold elevations in TNF-α secretion. IL-6 secretion was increased (48%, P=0.04) only by estrogen+progestin therapy. Although soluble receptor secretion was not different among groups, soluble TNF receptor type I and IL-6 receptor secretion were inversely related to plasma follicle stimulating hormone (P<0.05). Both therapies reduced plasma osteocalcin (a marker for osteoporosis) by ∼50% (P<0.002). Plasma C-reactive protein (CRP, a marker for cardiovascular risk) was 3-fold higher in women receiving only estrogen, compared to untreated women (P=0.01), and twice as high as those receiving estrogen+progestin (P=0.045). Simple linear relationships were not observed between cytokine secretion and these markers, but a significant HRT/TNF-α interaction with osteocalcin (P=0.022) and an HRT/IL-6 interaction with CRP (P=0.016) indicated more complex relationships between hormone replacement, cytokine activity, and health risks associated with menopause.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Molecular Biology