Preliminary report: effect of adrenal androgen and estrogen on bone maturation and bone mineral density
Abstract
To clarify the independent physiological roles of adrenal androgen and estrogen on bone growth, we compared the lumbar spine bone mineral density (BMD) in prepubertal girls with virilizing congenital adrenal hyperplasia (CAH) (n = 17) and girls with central precocious puberty (CPP) (n = 18). When BMD was analyzed according to chronologic age, no significant differences were found between CPP and CAH patients. However, when adjusted to bone age, BMD was statistically higher in CAH than in CPP subjects. This finding suggests that adrenal androgen, as well as estrogen, plays an important role in increasing BMD. Adrenal androgen may act on bone not only as androgen, but as estrogen after having been metabolized into an aromatized bone-active compound in peripheral tissues, such as bone and fat. Therefore, adrenal androgen may have a more important role in increasing BMD than previously realized.
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A few studies have reported normal or even high BMD, but most have shown low BMD at all or at least some sites in patients with CAH.
“A few studies have reported normal (704-709) or even high BMD (710), but most have shown low BMD at all or at least some sites (209,217,360,646,711-722).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [707]
Cites
Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994) · New England Journal of Medicine · doi:10.1056/nejm199410203311604 · Cited by 2,471 · see citing works
Morishima, A., Grumbach, M. M., Simpson, E. R., Fisher, C., & Qin, K. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.12.8530621 · Cited by 1,416 · see citing works
Increases in Bone Density During Treatment of Men with Idiopathic Hypogonadotropic Hypogonadism*
Finkelstein, J. S., Klibanski, A., Neer, R. M., Doppelt, S. H., Rosenthal, D. I., Segre, G. V., & Crowley, W. F. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-69-4-776 · Cited by 354 · see citing works
Zelissen, P. M. J., CROUGHS, R. J. M., van Rijk, P. P., & Raymakers, J. A. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-120-3-199402010-00005 · Cited by 220 · see citing works
Gonadal and Adrenal Androgens Are Potent Regulators of Human Bone Cell Metabolism In Vitro
Kasperk, C. H., Wakley, G. K., Hierl, T., & Ziegler, R. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.3.464 · Cited by 196 · see citing works
Aromatase in bone cell: Association with osteoporosis in postmenopausal women
Nawata, H., Tanaka, S., Tanaka, S., Takayanagi, R., Sakai, Y., Yanase, T., Ikuyama, S., & Haji, M. (1995) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(95)00031-t · Cited by 185 · see citing works
Peak bone mineral accrual and age at menarche in adolescent girls: A 6-year longitudinal study
McKay, H. A., Bailey, D. A., Mirwald, R. L., Davison, K. S., & Faulkner, R. A. (1998) · The Journal of Pediatrics · doi:10.1016/s0022-3476(98)70112-x · Cited by 153 · see citing works
Bone mineral density and body composition in congenital adrenal hyperplasia.
Cameron, F. J., Kaymakci, B., Byrt, E. A., Ebeling, P. R., Warne, G. L., & Wark, J. D. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.7.7608286 · Cited by 114 · see citing works
Hyams, J. S., & Carey, D. E. (1988) · The Journal of Pediatrics · doi:10.1016/s0022-3476(88)80260-9 · Cited by 109 · see citing works
Effect of testosterone on bone density and bone metabolism in adolescent male hypogonadism
Arisaka, O., Arisaka, M., Nakayama, Y., Fujiwara, S., & Yabuta, K. (1995) · Metabolism · doi:10.1016/0026-0495(95)90046-2 · Cited by 71 · see citing works
Self-citationBone mineral density during treatment of central precocious puberty
Neely, E. K., Bachrach, L. K., Hintz, R. L., Habiby, R. L., Slemenda, C. W., Feezle, L. K. S.-D., & Pescovitz, O. H. (1995) · The Journal of Pediatrics · doi:10.1016/s0022-3476(95)70182-6 · Cited by 66 · see citing works
Japanese Specific Bone Age Standard on the TW2
Murata, M. (1993) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.2.supple3_35 · Cited by 57 · see citing works
NAKAYAMA, Y., Arisaka, O., Shimura, N., Tokita, A., & Yamashiro, Y. (1998) · Endocrine Journal · doi:10.1507/endocrj.45.suppl_s183 · Cited by 11 · see citing works
Self-citationBone Mineralization and Bone Maturation in Precocious Puberty
Arisaka, O. (1997) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1997.02170380105019 · Cited by 7 · see citing works
Self-citationHosaka, A., & Arisaka, O. (1992) · Journal of Bone and Mineral Metabolism · doi:10.1007/bf02378981 · Cited by 3 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
Claahsen - van der Grinten, H. L., Speiser, P. W., Ahmed, S. F., Arlt, W., Auchus, R. J., Falhammar, H., Flück, C. E., Guasti, L., Huebner, A., Kortmann, B. B. M., et al. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab016 · Cited by 556 · see citing works
Lorenz‐Depiereux, B., Bastepe, M., Benet‐Pagès, A., Amyere, M., Wagenstaller, J., Mueller-Barth, U., Badenhoop, K. W. J., Kaiser, S., Rittmaster, R. S., Shlossberg, A. H., et al. (2006) · Nature Genetics · doi:10.1038/ng1868 · Cited by 528 · see citing works
Yılmaz, D. Ç., Ersoy, B., Bilgin, E. S., Gümüşer, G., Onur, E., & Dündar, E. P. (2005) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-005-0631-6 · Cited by 163 · see citing works
Fractures and bone mineral density in adult women with 21-hydroxylase deficiency
Falhammar, H., Filipsson, H., Holmdahl, G., Janson, P.-O., Nordenskjöld, A., Hagenfeldt, K., & Thorén, M. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0744 · Cited by 151 · see citing works
Stikkelbroeck, N. M. M. L., Oyen, W. J. G., van der Wilt, G.-J., Hermus, A. R. M. M., & Otten, B. J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021074 · Cited by 138 · see citing works
Clinical outcomes in the management of congenital adrenal hyperplasia
Falhammar, H., & Thorén, M. (2012) · Endocrine · doi:10.1007/s12020-011-9591-x · Cited by 106 · see citing works
King, J. A., Wisniewski, A. B., Bankowski, B. J., Carson, K. A., Zacur, H. A., & Migeon, C. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0745 · Cited by 101 · see citing works
Chakhtoura, Z., Bachelot, A., Samara-Boustani, D., Ruiz, J.-C., Donadille, B., Dulon, J., Christin-Maître, S., Bouvattier, C., Raux-Demay, M.-C., Bouchard, P., et al. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0887 · Cited by 90 · see citing works
Bone mineral density, bone markers, and fractures in adult males with congenital adrenal hyperplasia
Falhammar, H., Filipsson Nyström, H., Wedell, A., Brismar, K., & Thorén, M. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0865 · Cited by 82 · see citing works
Sciannamblo, M., Russo, G., Cuccato, D., Chiumello, G., & Mora, S. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2823 · Cited by 82 · see citing works
Remer, T., Boye, K. R., Hartmann, M. F., Neu, C. M., Schöenau, E., Manz, F., & Wudy, S. A. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.8.1539 · Cited by 62 · see citing works
Rangaswamaiah, S., Gangathimmaiah, V., Nordenstrom, A., & Falhammar, H. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00493 · Cited by 59 · see citing works
Long-Term Outcome of Patients With Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency
Mnif, M. F., Kamoun, M., Mnif, F., Charfi, N., Kallel, N., Naceur, B. B., Rekik, N. M., Abid, M., Mnif, Z., Sfar, M. H., et al. (2012) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31824369e4 · Cited by 49 · see citing works
Glucocorticoid-Induced Osteoporosis in Children with 21-Hydroxylase Deficiency
Ventura, A., Brunetti, G., Colucci, S. C., Oranger, A., Ladisa, F., Cavallo, L., Grano, M., & Faienza, M. F. (2012) · BioMed Research International · doi:10.1155/2013/250462 · Cited by 45 · see citing works
Claahsen-van der Grinten, H. L., Noordam, K., Borm, G. F., & Otten, B. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1701 · Cited by 42 · see citing works
Challenges in treatment of patients with non-classic congenital adrenal hyperplasia
Adriaansen, B. P. H., Schröder, M. A. M., Span, P. N., Sweep, F. C. G. J., van Herwaarden, A. E., & der Grinten, H. L. C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1064024 · Cited by 40 · see citing works
Khalid, W., Maqbool, Z., Arshad, M. S., Kousar, S., Akram, R., Siddeeg, A., Ali, A., Qin, H., Aziz, A., Saeed, A., et al. (2022) · International Journal of Food Properties · doi:10.1080/10942912.2022.2070643 · Cited by 24 · see citing works
RetractedLong‐term health consequences of congenital adrenal hyperplasia
Pofi, R., Ji, X., Krone, N. P., & Tomlinson, J. (2023) · Clinical Endocrinology · doi:10.1111/cen.14967 · Cited by 24 · see citing works
Remer, T., Manz, F., Hartmann, M. F., Schöenau, E., & Wudy, S. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1375 · Cited by 24 · see citing works
Congenital adrenal hyperplasia: transitional care
Hughes, I. A. (2004) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2004.03.015 · Cited by 22 · see citing works
Bachelot, A., Chakhtoura, Z., Samara‐Boustani, D., Dulon, J., Touraine, P. A., & Polak, M. (2010) · International Journal of Pediatric Endocrinology · doi:10.1155/2010/326275 · Cited by 23 · see citing works
The pathogenesis of osteoporosis in older women and men: a review
Enriori, P. J., & Enriori, C. L. (2002) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(02)00144-9 · Cited by 15 · see citing works
Çetinkaya, S. Ç., & Kara, C. (2011) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2011.189 · Cited by 14 · see citing works
Vandewalle, S., Taes, Y., Fiers, T., Toye, K. R. C., Caenegem, E. V., Kaufman, J., & Schepper, J. D. (2014) · Bone · doi:10.1016/j.bone.2014.09.002 · Cited by 12 · see citing works
Dayem, S. M. A. E., Anwar, G. M., Salama, H. M., Kamel, A. F., & Emara, N. A. (2010) · Archives of Medical Science · doi:10.5114/aoms.2010.13516 · Cited by 12 · see citing works
Adrenal Steroid Hormones and Metaphyseal Bone in Children
Remer, T., Boye, K. R., Hartmann, M. F., Neu, C. M., Schöenau, E., Manz, F., & Wudy, S. A. (2004) · Hormone Research in Paediatrics · doi:10.1159/000081349 · Cited by 11 · see citing works
Gao, Y., Wang, O., Guan, W., Wu, X., Mao, J., Wang, X., Yu, W., & Nie, M. (2020) · Clinical Endocrinology · doi:10.1111/cen.14391 · Cited by 11 · see citing works
Bone mineral density in young adult women with congenital adrenal hyperplasia
Jyotsna, V., Raizada, N., Upadhyay, A. D., & Gupta, N. C. (2015) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.172283 · Cited by 10 · see citing works
Bachelot, A., Chakhtoura, Z., Samara‐Boustani, D., Dulon, J., Touraine, P. A., & Polak, M. (2010) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2010-326275 · Cited by 9 · see citing works
Yang, T., Chen, Y., Liang, W.-H., Chang, C., Tai, L.-C., Chang, S.-P., & Ng, H. (2007) · Journal of the Chinese Medical Association · doi:10.1016/s1726-4901(09)70358-2 · Cited by 7 · see citing works
Genton, L., Raguso, C. A., Berney, T., Hans, D. B., Morel, P., & Pichard, C. (2003) · Gut · doi:10.1136/gut.52.5.659 · Cited by 7 · see citing works
Sun, X., Wu, Y., Lü, L., Xia, W., Zhang, L., Chen, S., Nie, M., Zheng, G., Su, W., Zhu, H., et al. (2023) · Calcified Tissue International · doi:10.1007/s00223-023-01132-w · Cited by 5 · see citing works
Hypothalamic–Pituitary–Adrenal Axis: Congenital Adrenal Hyperplasia
Pasterski, V., & Hughes, I. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00070-5 · Cited by 5 · see citing works
Ünal, S., Alikaşifoğlu, A., Özön, A., Gonc, N. E., & Kandemir, N. (2020) · The Turkish Journal of Pediatrics · doi:10.24953/turkjped.2020.03.002 · Cited by 5 · see citing works
Kenny, A. M., & Raisz, L. G. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-388-0_11 · Cited by 5 · see citing works
Kim, K., Kyung, S., Jang, M., Ji, S., Lee, D. H., Yoon, H. M., & Kim, N. (2023) · Journal of Imaging Informatics in Medicine · doi:10.1007/s10278-023-00849-2 · Cited by 4 · see citing works
Antoniazzi, F., Monti, E., Gaudino, R., Cavarzere, P., Zaffanello, M., Brugnara, M., Perlini, S., Maines, E., Gallo, M. C., Corso, S. D., et al. (2010) · Expert Review of Endocrinology & Metabolism · doi:10.1586/eem.09.82 · Cited by 3 · see citing works
Fava, D., Casirati, A., Angelelli, A., Calevo, M. G., Pepino, C., Pepe, A., Maiorano, N. G., Acquarone, L., Repetto, A., Santucci, C., et al. (2026) · Journal of the Endocrine Society · doi:10.1210/jendso/bvag023 · Cited by 2 · see citing works
Platnick, C., Choi, Y. J., Narongkiatikhun, P., Bekelman, N. J., Rountree-Jablin, C., Birznieks, C. L., Sell, E., Tommerdahl, K. L., de Boer, I. H., Shah, V. N., et al. (2025) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2024-0254 · Cited by 2 · see citing works
Congenital Adrenal Hyperplasia in Adults
Falhammar, H. (2010) · Figshare · Cited by 2 · see citing works
Kanazawa, S. (2002) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.11.11 · Cited by 2 · see citing works
Self-citationGorrigan, R. J., Todd, B., Honour, J. W., & Hindmarsh, P. C. (2026) · JCEM Case Reports · doi:10.1210/jcemcr/luag036 · Cited by 1 · see citing works
Silva, R. S., Fontoura, M., Severo, M., Lucas, R., & Santos, A. C. (2022) · European Journal of Pediatrics · doi:10.1007/s00431-022-04442-7 · Cited by 1 · see citing works
Another issue in traditional medical therapy for congenital adrenal hyperplasia
Arisaka, O., Numata, M., Hoshi, M., & Kanazawa, S. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.118424 · Cited by 1 · see citing works
Self-citationKanazawa, S., Kojima, M., Koyama, S., & Arisaka, O. (2004) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.13.79
Self-citationArisaka, O., Kanno, H., Negishi, M., Kojima, M., Nishikura, K., Numata, M., Kanazawa, S., Nitta, A., Kuribayashi, T., & Kano, K. (2002) · Metabolism · doi:10.1053/meta.2002.35590
Self-citationNermoen, I. (2013) · NORA - Norwegian Open Research Archives
Ghaemi, N., Malek, A., Setare, S. H., & Shaye, Z. A. (2021) · DOAJ (DOAJ: Directory of Open Access Journals) · doi:10.22038/ijp.2021.54310.4294
Sun, X., Wu, Y., Lü, L., Xia, W., Zhang, L., Chen, S., Nie, M., Zheng, G., Su, W., Zhu, H., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1587674/v1
ElBakry, N. M., Khalf, A., Ameen, M., & Mahgoob, M. H. (2025) · Cureus · doi:10.7759/cureus.83778
- Authors
- Arisaka, O., Hoshi, M., Kanazawa, S., Numata, M., Nakajima, D., Kanno, S., Negishi, M., Nishikura, K., Nitta, A., Imataka, M., Kuribayashi, T., & Kano, K.
- Affiliations
- Dokkyo University (JP)
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 50
- Issue
- 4
- Pages
- 377-379
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2089052804
- Cited by
- 50
- References
- 15
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 3 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 4
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- estrogen, bone mineral density, skeletal maturation, congenital adrenal hyperplasia, central precocious puberty, prepubertal girls, bone age, aromatization, sex steroids
- MeSH terms
- Adrenal Glands, Adrenal Hyperplasia, Congenital, Age Determination by Skeleton, Androgens, Bone Development, Child, Estrogens, Female, Humans, Puberty, Precocious, Absorptiometry, Photon, Bone Density
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