Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men

J Clin Endocrinol Metab. 2002 Apr;87(4):1550-4. doi: 10.1210/jcem.87.4.8397.

Abstract

Recent studies have shown that estrogen (E) likely plays a dominant role in inhibiting bone resorption in normal elderly men. Because both E and T inhibit osteoclast development and activity, stimulate osteoclast apoptosis, and inhibit osteoblast production of IL-6, it is unclear why T is less potent than E in inhibiting bone resorption in vivo. Osteoprotegerin (OPG) binds to and inactivates RANKL, the final mediator of osteoclastogenesis. In vitro, OPG production is stimulated by E, and preliminary data suggest that T has the opposite effect. Thus, we analyzed serum for OPG levels from a study in which 59 elderly men (mean age, 68 yr) were made acutely hypogonadal using a GnRH agonist and were also placed on an aromatase inhibitor to block conversion of androgens to estrogens. They were studied first under conditions of physiologic E and T replacement, and then randomized to no replacement, replacement with E alone, T alone, or both E and T. E alone resulted in an 18.6 +/- 7.9% (mean +/- SEM) increase in serum OPG levels (P < 0.05), whereas T alone tended to decrease OPG levels (by 10.0 +/- 8.5%; P < 0.05 compared with E alone). Using a two-factor ANOVA model, there was a highly significant T effect (P = 0.006) on decreasing serum OPG levels. Serum TNF-alpha, IL-6, and IL-6 soluble receptor levels increased significantly in the men who had both E and T withdrawn, and the increases in TNF-alpha and IL-6sR were absent in the men treated with either E or T. However, due to the variability in these cytokine measurements, the ANOVA models were not significant for E or T effects. Taken together, these data suggest that in vivo, T decreases OPG levels, whereas E tends to have the opposite effect. These differential effects of E vs. T on OPG production may explain, at least in part, why T has weaker effects than E on inhibiting bone resorption in vivo in humans.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Bone Resorption / metabolism
  • Cytokines / blood*
  • Estrogens / pharmacology*
  • Glycoproteins / blood*
  • Gonadal Steroid Hormones / pharmacology*
  • Humans
  • Male
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear / blood*
  • Receptors, Tumor Necrosis Factor
  • Reference Values
  • Testosterone / pharmacology*

Substances

  • Biomarkers
  • Cytokines
  • Estrogens
  • Glycoproteins
  • Gonadal Steroid Hormones
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11B protein, human
  • Testosterone