Impact of menopausal hormonal and nonhormonal therapy on cytokine production with pe-ripheral blood cells in postmenopausal women

Objective. To comparatively analyze the levels of cytokines (TNF-α, IL-6, and IFN-γ) in the serum and peripheral blood cell culture supernatants of women using the drugs of menopausal hormonal (Πβ-estradiol 1 mg + dydrogesterone 5 mg) and nonhormonal (genistein 60 mg) therapy and to study the relationship of their concentrations to the serum levels of pregnancy-associated α -glycoprotein (PAG). Subjects and methods. The levels of cytokines (TNF-α, IL-6, and IFN-γ) and PAG in the serum and cell culture supernatants (spontaneous and mitogen-induced cytokine production) were determined in 15 healthy women and 40 patients with moderate menopausal syndrome, who received hormonal (17ß-estradiol 1 mg + dydrogesterone 5 mg) and nonhormonal (genistein 60 mg) therapy for 3-6 months and for 2-5 years. Results. It was ascertained that there were increases in the stimulation index of TNF-α and IFN-γ and in mitogen-activated IFN-γ synthesis and a decrease in spontaneous IL-6 synthesis when a hormonal drug was used for 3-6 months. The administration of a nonhormonal drug for the same period reduced mitogen-induced synthesis and stimulation index for TNF-α. The use of a hormonal drug for 2-5 years failed to affect the functional activity of blood cells and the production of the study cytokines. Serum PAG concentrations were elevated in 26.3% of the women taking a hormonal drug for 3-6 months and in 40% of those using the same agent for 2-5 years. A correlation was established between blood PAG levels and mitogen-induced cytokine production: it was positive with TNF-α (r = 0.41; p = 0.037) and negative with IFN-γ (r = -0.4; p = 0.03) in the use of hormonal drugs regardless of its duration. Conclusion. The found correlations between the levels of cytokines (TNF-α and IFN-γ) in the mitogen-induced culture supernatants and the concentrations of the pregnancy protein PAG in the serum could identify a group at risk for oncoproliferative processes in the estrogen-dependent organs during menopausal hormonal therapy for more than 2 years.

menopausal syndrome, menopausal hormonal and nonhormonal therapy, cytokines, pregnancy-associated α-glycoprotein