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  • Review Article
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Estrogens as regulators of bone health in men

Nature Reviews Endocrinology volume 5, pages 437–443 (2009)Cite this article

Abstract

Bone metabolism is influenced by sex steroids during growth and adulthood in both men and women. Although this influence is well described in women, the relative importance of androgens and estrogens in the regulation of the male skeleton remains uncertain. Even though estradiol has been considered the 'female hormone', levels of serum estradiol in elderly men are higher than those in postmenopausal women. Estradiol levels are more strongly associated with BMD, bone turnover and bone loss than testosterone levels are in adult men. Case reports of young men with estrogen resistance or aromatase deficiency also suggest a crucial role for estradiol in regulation of skeletal growth in men. Moreover, serum levels of both estrogens and androgens are inversely associated with the risk of fracture in aging men. A large, prospective, population-based study showed that levels of serum estradiol predict the risk of fracture, independently of serum testosterone. Evidence suggests that a threshold level of estradiol exists below which the male skeleton is impaired; rates of bone loss and fracture seem to be increased and bone maturation delayed in men with estradiol levels below this threshold. On the basis of these findings, we propose that not only androgens, but also estrogens, are important regulators of bone health in men.

Key Points

  • Sex steroids influence growth and maintenance of the skeleton in both men and women

  • Serum levels of estradiol are higher in aging men than in postmenopausal women

  • Studies of men with estrogen resistance or aromatase deficiency demonstrated the importance of estrogens in skeletal maturation and growth-plate closure in men, which led to a paradigm shift

  • Cross-sectional and longitudinal studies showed that serum levels of estrogens are more strongly associated with BMD and bone loss than levels of androgens are in adult and aging men

  • Serum levels of both androgens and estrogens are inversely associated with incident fractures in elderly men

  • Recent evidence suggests that a threshold level exists for estradiol in adult men; subthreshold levels are associated with increased fracture risk, bone loss and delayed bone maturation

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Figure 1: Bioavailable estradiol levels in three groups of men (young, aged 22–39 years; middle-aged, aged 40–59 years; and elderly, aged 60–90 years) and in premenopausal and postmenopausal women from Rochester, MN.
Figure 2: Proposed estradiol threshold levels for bone health in men.
Figure 3: Effects of serum sex-steroid levels on fracture risk in elderly men in the MrOS Sweden study.59

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Acknowledgements

The authors' own work cited in this Review was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, The ALF–LUA research grant in Gothenburg, the Lundberg Foundation, and the Torsten and Ragnar Söderberg's Foundation.

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  1. Department of Internal Medicine, Center for Bone Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Liesbeth Vandenput & Claes Ohlsson

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Correspondence to Claes Ohlsson.

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Vandenput, L., Ohlsson, C. Estrogens as regulators of bone health in men. Nat Rev Endocrinol 5, 437–443 (2009). https://doi.org/10.1038/nrendo.2009.112

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