Background/Aims: Previous studies on the effects of estrogen on sclerostin regulation were conducted in postmenopausal women in humans or animals following estrogen treatment or induced estrogen deficiency. The aim of this study was to evaluate the effects of sex hormones on serum sclerostin levels in premenopausal women with normal menstrual cycles. Methods: A prospective observational clinical study. 80 voluntary premenopausal women were recruited for the study. Data from 31 patients were available for the statistical analysis. Serum sclerostin, free estradiol, free testosterone, and progesterone levels were measured during the menstruation, late follicular and mid-luteal phases. The unique protocol IDs were BEAH FTR-4 and NCT01418924 at ClinicalTrials.gov ID. Results: Serum sclerostin values were 1.03 ± 0.58 ng/ml during the menstruation phase, 1.0 ± 0.36 ng/ml during the late follicular phase, and 1.18 ± 0.67 ng/ml during the mid-luteal phase (p = 0.543). There was no significant relationship between serum levels of sex steroids and sclerostin. Conclusions: Previous studies have not investigated the impact of sex hormone fluctuations on serum sclerostin levels during the menstrual cycle. The present study shows that serum sclerostin levels were not affected by sex steroids in premenopausal women with normal menstrual cycles.

Keywords:
Sclerostin, Premenopause, Estrogen, Progesterone, Androgen
1.
Moester MJ, Papapoulos SE, Löwik CW, van Bezooijen RL: Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 2010;87:99-107.
2.
Agholme F, Aspenberg P: Wnt signaling and orthopedics, an overview. Acta Orthop 2011;82:125-130.
3.
Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, et al: Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 2008;23:860-869.
4.
Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, et al: Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001;10:537-543.
5.
Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, et al: Mechanical stimulation of bone in vivo reduces osteocyte expression of SOST/sclerostin. J Biol Chem 2008;283:5866-5875.
6.
Moustafa A, Sugiyama T, Saxon LK, Zaman G, Sunters A, et al: The mouse fibula as a suitable bone for the study of functional adaptation to mechanical loading. Bone 2009;44:930-935.
7.
Suva LJ: Sclerostin and the unloading of bone. J Bone Miner Res 2009;24:1649-1650.
8.
Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, et al: Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 2010;95:2248-2253.
9.
Lin C, Jiang X, Dai Z, Guo X, Weng T, et al: Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/β-catenin signaling. J Bone Miner Res 2009;24:1651-1661.
10.
Price JS, Sugiyama T, Galea GL, Meakin LB, Sunters A, et al: Role of endocrine and paracrine factors in the adaptation of bone to mechanical loading. Curr Osteoporos Rep 2011;9:76-82.
11.
Mabilleau G, Mieczkowska A, Edmonds ME: Treatment thiazolidinediones induce osteocyte apoptosis and increase sclerostin expression. Diabet Med 2010;27:925-932.
12.
Zaman G, Saxon LK, Sunters A, Hilton H, Underhill P, et al: Loading-related regulation of gene expression in bone in the contexts of estrogen deficiency, lack of estrogen receptor-α and disuse. Bone 2010;46:628-642.
13.
Chung YE, Lee SH, Lee SY, Kim SY, Kim HH, et al: Long-term treatment with raloxifene, but not bisphosphonates, reduces circulating sclerostin levels in postmenopausal women. Osteoporos Int 2012;23:1235-1243.
14.
Mödder UI, Clowes JA, Hoey K, Peterson JM, McCready L, et al: Regulation of circulating sclerostin levels by sex steroids in women and in men. J Bone Miner Res 2011;26:27-34.
15.
Mödder UI, Roforth MM, Hoey K, McCready LK, Peterson JM, et al: Effects of estrogen on osteoprogenitor cells and cytokines/bone-regulatory factors in postmenopausal women. Bone 2011;49:202-207.
16.
Callewaert F, Bakker A, Schrooten J, Van Meerbeek B, Verhoeven G, et al: Androgen receptor disruption increases the osteogenic response to mechanical loading in male mice. J Bone Miner Res 2010;25:124-131.
17.
Van Hooff MH, Voorhorst FJ, Kaptein MB, Hirasing RA, Koppenaal C, et al: Predictive value of menstrual cycle pattern, body mass index, hormone levels and polycystic ovaries at age 15 years for oligo-amenorrhoea at age 18 years. Hum Reprod 2004;19:383-392.
18.
Gower BA, Nyman L: Associations among oral estrogen use, free testosterone concentration, and lean body mass among postmenopausal women. J Clin Endocrinol Metab 2000;85:4476-4480.
19.
Miller KK, Rosner W, Lee H, Hier J, Sesmilo G, et al: Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods. J Clin Endocrinol Metab 2004;89:525-533.
20.
Huber C, Collishaw S, Mosley JR, Reeve J, Noble BS: Selective estrogen receptor modulator inhibits osteocyte apoptosis during abrupt estrogen withdrawal: implications for bone quality maintenance. Calcif Tissue Int 2007;81:139-144.
21.
Seo SK, Yang HI, Lim KJ, Jeon YE, Choi YS, Cho S, Lee BS: Changes in serum levels of cartilage oligomeric matrix protein after estrogen and alendronate therapy in postmenopausal women. Gynecol Obstet Invest 2012;4:143-150.
22.
Mirza FS, Padhi ID, Raisz LG, Lorenzo JA: Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 2010;95:1991-1997.
23.
Mödder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, et al: Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 2011;26:373-379.
24.
Miro F, Parker SW, Aspinall LJ, Coley J, Perry PW, et al: Relationship between follicle-stimulating hormone levels at the beginning of the human menstrual cycle, length of the follicular phase and excreted estrogens: the FREEDOM study. J Clin Endocrinol Metab 2004;89:3270-3275.
25.
Barnett JB, Woods MN, Lamon-Fava S, Schaefer EJ, McNamara JR, et al: Plasma lipid and lipoprotein levels during the follicular and luteal phases of the menstrual cycle. J Clin Endocrinol Metab 2004;89:776-782.
26.
Wells G, Herrington DM: The Heart and Estrogen/Progestin Replacement Study: what have we learned and what questions remain? Drugs Aging 1999;15:419-422.
27.
Stevenson JC: A woman's journey through the reproductive, transitional and postmenopausal periods of life: impact on cardiovascular and musculo-skeletal risk and the role of estrogen replacement. Maturitas 2011;70:197-205.
28.
Lasley BL, Santoro N, Randolf JF, Gold EB, Crawford S, et al: The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity. J Clin Endocrinol Metab 2002;87:3760-3767.
29.
Barbieri RL: Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 1992;166:740-745.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.