|
|
|
| Effect of sex hormones on male osteoporosis: a review |
| GAO Zengjie1,2, ZHANG Wangming1, FAN Zhiliang2, LI Lailai2, CHAI Yihui2
|
1. Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, Guizhou 550014, China;
2. Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China |
|
|
|
|
Abstract The incidence of fragility fractures and related mortality caused by male osteoporosis (OP) are both higher than in females. Male bone health was regulated by a sophisticated network involving both androgens and estrogens. Androgens can directly promote bone formation and inhibit bone resorption through androgen receptors on osteoblasts and osteocytes. They can also be converted into estrogens via the action of aromatase and subsequently regulate bone metabolism through estrogen receptors. Declining sex hormone levels, an imbalance in the estrogen-to-androgen ratio, and the resulting disruption in bone metabolic pathways collectively contribute to the development and progression of male OP. Moreover, androgens cannot fully compensate for the bone metabolic imbalance induced by estrogen deficiency. This article reviewed research on the role and mechanism of sex hormones in male OP, as well as studies related to the risks of sex hormone therapy for OP, so as to provide the references for improving control and treatment strategies of male OP.
|
|
Received: 16 June 2025
Revised: 29 October 2025
Published: 25 December 2025
|
|
|
|
|
|
[1] HUANG C F,HO C J,LIN S Y,et al.Asia-Pacific consensus for the management of osteoporosis in men[J].Osteoporos Int,2025,36(7):1105-1114.
[2] NASO C M,LIN S Y,SONG G,et al.Time trend analysis of osteoporosis prevalence among adults 50 years of age and older in the USA,2005-2018[J].Osteoporos Int,2025,36(3):547-554.
[3] DE MARTINIS M,SIRUFO M M,POLSINELLI M,et al.Gender differences in osteoporosis:a single-center observational study[J].World J Mens Health,2021,39(4):750-759.
[4] SEBO Z L,RODEHEFFER M S.Testosterone metabolites differentially regulate obesogenesis and fat distribution[J/OL].Mol Metab,2021,44[2025-10-29] .https://doi.org/10.1016/j.molmet.2020.101141.
[5] LAN K C,WEI K T,LIN P W,et al.Targeted activation of androgen receptor signaling in the periosteum improves bone fracture repair[J/OL].Cell Death Dis,2022,13(2)[2025-10-29] .https://doi.org/10.1038/s41419-022-04595-1.
[6] AMANO T.Late-onset hypogonadism:current methods of clinical diagnosis and treatment in Japan[J].Asian J Androl,2025,27(4):447-453.
[7] CORONA G,VENA W,PIZZOCARO A,et al.Testosterone supplementation and bone parameters:a systematic review and meta-analysis study[J].J Endocrinol Invest,2022,45(5):911-926.
[8] THEODORAKIS N,FERETZAKIS G,VAMVAKOU G,et al.Testosterone therapy for functional hypogonadism in middle-aged and elderly males:current evidence and future perspectives[J].Hormones(Athens),2024,23(4):801-817.
[9] SHI V,MORGAN E F.Estrogen and estrogen receptors mediate the mechanobiology of bone disease and repair[J/OL].Bone,2024,188[2025-10-29] .https://doi.org/10.1016/j.bone.2024.117220.
[10] TIAN X,ZHANG B.The association between sex hormones and bone mineral density in US females[J/OL].Sci Rep,2025,15(1)[2025-10-29] .https://doi.org/10.1038/s41598-025-89985-z.
[11] JIN H,CHEN M,WANG X,et al.Estrogen deficiency impairs double-negative T cell function and activates NF-κB in postmenopausal osteoporosis[J/OL].Biochem Biophys Res Commun,2025,776[2025-10-29] .https://doi.org/10.1016/j.bbrc.2025.152212.
[12] TENUTA M,HASENMAJER V,GIANFRILLI D,et al.Testosterone and male bone health:a puzzle of interactions[J].J Clin Endocrinol Metab,2025,110(7):2121-2135.
[13] GRIGORYAN S,CLINES G A.Hormonal control of bone architecture throughout the lifespan:implications for fracture prediction and prevention[J].Endocr Pract,2024,30(7):687-694.
[14] WANG Z X,CHEN K,WU C C,et al.An emerging role of Prevotella histicola on estrogen deficiency-induced bone loss through the gut microbiota-bone axis in postmenopausal women and in ovariectomized mice[J].Am J Clin Nutr,2021,114(4):1304-1313.
[15] FENG C,XU Z,TANG X,et al.Estrogen-related receptor α:a significant regulator and promising target in bone homeostasis and bone metastasis[J/OL].Molecules,2022,27(13)[2025-10-29] .https://doi.org/10.3390/molecules27133976.
[16] 李娜,代晓霞.Runx2在骨形成中的作用及调控[J].国外医学(医学地理分册),2018,39(4):353-356.
LI N,DAI X X.Role and regulation of Runx2 in bone formation[J].Foreign Med Sci(Sect Medgeogr),2018,39(4):353-356.(in Chinese)
[17] BASHEER B,ILA V,BARROS R,et al.Management of adverse effects in testosterone replacement therapy[J/OL].Int Braz J Urol,2025,51(3)[2025-10-29] .https://doi.org/10.1590/S1677-5538.IBJU.2025.9904.
[18] MELLSTRÖM D,VANDENPUT L,MALLMIN H,et al.Older men with low serum estradiol and high serum SHBG have an increased risk of fractures[J].J Bone Miner Res,2008,23(10):1552-1560.
[19] CALLEWAERT F,SINNESAEL M,GIELEN E,et al.Skeletal sexual dimorphism:relative contribution of sex steroids,GH-IGF1,and mechanical loading[J].J Endocrinol,2010,207(2):127-134. |
|
|
|
