Estrogen and the Male Skeleton

Khosla, Sundeep; Melton, L. Joseph; Riggs, B. Lawrence

doi:10.1210/jcem.87.4.8417

Cited by 308Bone health and osteoporosis researchHormonal and reproductive studiesEstrogen and related hormone effects

Estrogen and the Male Skeleton

Khosla, Sundeep, Melton, L. Joseph, Riggs, B. Lawrence·2002·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jcem.87.4.8417

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Abstract

Because estrogen (E) and T are the major sex steroids in women and men, respectively, the traditional view had been that E primarily regulated bone turnover in women and T played the analogous role in men. The description of ER- deficient and aromatase-deficient males, however, initiated a major shift in our thinking on the relative roles of T and E in regulating the male skeleton, because these individuals all had unfused epiphyses, high bone turnover, and osteopenia. Similar, albeit less striking, findings were noted in mouse models with knock-out of either the ER-alpha or the aromatase genes. Although these human experiments of nature and mouse knock-out models clearly demonstrated an important role for E in the growth and maturation of the male skeleton, they did not define the role of E vs. T in regulating the adult male skeleton. The past several years have witnessed an accumulation of evidence from observational as well as direct interventional studies that now clearly indicates that E plays a major, and likely dominant, role in bone metabolism in men. These data also suggest that a threshold level of bioavailable (or non-SHBG bound) E is needed for skeletal E sufficiency in the male, and that with aging, an increasing percentage of elderly men begin to fall below this level. It is this subset of men who may be at greatest risk for the development of age-related bone loss and osteoporosis. Moreover, these men may also be the ones most likely to respond favorably to treatment with selective E receptor modulators, or perhaps even to T replacement, because the skeletal effects of the latter may be mediated largely via aromatization to E.

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Estradiol levels may be more important for skeletal health in men than testosterone levels, based on evidence from aromatase-deficient men, disrupted estrogen signaling, and observational studies.
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Authors: Khosla, S., Melton, L. J., & Riggs, B. L.
Affiliations: Mayo Clinic (US)
Corresponding author: Khosla, Sundeep
ORCID: Khosla, Sundeep
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2002-04-01
Volume: 87
Issue: 4
Pages: 1443-1450
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jcem.87.4.8417
OpenAlex: W1999519119
Cited by: 308
References: 59
Citations by year: 2026: 4 · 2025: 2 · 2024: 8 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 10 · 2016: 5 · 2015: 3 · 2014: 10 · 2013: 12 · 2012: 13
FWCI: 28.89
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (P01AG004875)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR027065)
Topics: Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords: estrogen, male skeleton, bone metabolism, bone turnover, aromatase, estrogen receptor alpha, testosterone, sex steroids, epiphyseal fusion, osteopenia, older men, age-related bone loss, osteoporosis, selective estrogen receptor modulators, testosterone replacement therapy, aromatization
MeSH terms: Animals, Bone and Bones, Estrogens, Humans, Male, Osteoporosis, Sex Characteristics

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Estrogen and the Male Skeleton

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