Sex differences in the serum level of endogenous ligands for estrogen receptor β in the elderly population

Animal studies suggest that estrogen receptor β (ERβ)-agonists, but not ERα-agonists, are antidepressants. Several endogenous ligands for ERβ have been proposed, including 5α-androstane-3β, 17β-diol (3βAdiol), Androstenediol (Δ5-diol), and 7α-hydroxydehydroepiandrosterone (7α-OH-DHEA). The aim of this study was to determine the serum and salivary levels of natural ERβ ligands in men and women with and without past depressive episodes in the elderly population. DHEA (a precursor of 3βAdiol, Δ5-diol, and 7α-OH-DHEA), 17β-estradiol (E2), and cortisol (F) were also measured. Samples were collected from 51 subjects and liquid chromatography tandem mass spectrometry was used for measurement. Comparisons were made between groups based on sex and depression history. E2, 3βAdiol, and Δ5-diol levels were significantly lower in women than in men regardless of depression history. There were no significant differences between men and women in DHEA or 7α-OH-DHEA levels. DHEA was significantly lower in women with depression than in women without depression. Reduced DHEA levels may be related to depression vulnerability in women. Further studies are needed to determine the mechanism underlying sex differences in the prevalence of depression and increased risk of depression during menopause. Not only E2 but also two other estrogenic steroids (3βAdiol and Δ5-diol) should be involved in these studies.