Abstract
Purpose
Several clinical studies testify the critical role played by estrogens in male bone metabolism. The aim of our study is to assess the effect of a single injection of testosterone enanthate in a group of hypogonadal men on 17β estradiol serum levels and some bone metabolic parameters.
Method
Twenty-one hypogonadal males were given one testosterone enanthate injection (250 mg). Blood samples were drawn before the injection and after 1, 2 and 3 weeks. The following variables were measured: Total testosterone (TT), 17β estradiol (17β E2), Sex hormone binding globulin, total alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen (CTx).
Results
After testosterone injection, both TT and 17β E2 increased, peaking 1 week after the injection. Individual observation of the response of 17β E2 to testosterone showed that a subgroup (n = 9) failed to respond with any increase in 17β E2 at any of the weekly tests (group E2−), while the remainder (n = 12) showed a significant increase in 17β E2, which reached a mean value three times higher than at baseline (group E2+). The E2− patients reached a TT peak lower than that observed in the E+ group. CTx serum levels declined progressively in the E2+ group, reaching the significance (p = 0.03) at the end of the study, while it did not change in E− group.
Conclusion
This study suggests that a single injection of testosterone might have different effects on the production of endogenous estrogens, and a significant reduction of bone resorption parameters takes place only in the patients who show a significant increase of 17ß estradiol in response to testosterone administration.
Similar content being viewed by others
References
Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C (2004) Androgens and bone. Endocr Rev 25:389–425
Bouillon R, Bex M, Vanderschueren D, Boonen S (2004) Estrogens are essential for male pubertal periosteal bone expansion. J Clin Endocrinol Metab 89:6025–6029
Taes Y, Lapauw B, Vandewalle S, Zmierczak H, Goemaere S, Vanderschueren D, Kaufman JM, T’Sjoen G (2009) Estrogen-specific action on bone geometry and volumetric bone density, longitudinal observations in an adult with complete androgen insensitivity. Bone 45:392–397
Meier C, Nguyen TV, Handelsman DJ, Schindler C, Kushnir MM, Rockwood AL, Meikle AW, Center JR, Eisman JA, Seibel MJ (2008) Endogenous sex hormones and incident fracture risk in older men, the Dubbo Osteoporosis Epidemiology Study. Arch Intern Med 14:47–54
Bjørnerem A, Ahmed LA, Joakimsen RM, Berntsen GK, Fønnebø V, Jørgensen L, Øian P, Seeman E, Straume B (2007) A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men, the Tromso Study. Eur J Endocrinol 157:119–125
Goderie-Plomp HW, van der Klift M, de Ronde W, Hofman A, de Jong FH, Pols HA (2004) Endogenous sex hormones, sex hormone-binding globulin, and the risk of incident vertebral fractures in elderly men and women, the Rotterdam Study. J Clin Endocrinol Metab 89:3261–3269
Amin S, Zhang Y, Felson DT, Sawin CT, Hannan MT, Wilson PW, Kiel DP (2006) Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. Am J Med 119:426–433
Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S (2007) Estrogen prevents bone loss via estrogen receptor α and induction of Fas ligand in osteoclasts. Cell 130:811–823
Martin-Millan M, Almeida M, Ambrogini E, Han L, Zhao H, Weinstein RS, Jilka RL, O’Brien CA, Manolagas SC (2010) The estrogen receptor α in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol 24:323–334
Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C (2004) Androgens and bone. Endocr Rev 25:389–425
Lin IC, Slemp AE, Hwang C, Sena-Esteves M, Nah HD, Kirschner RE (2007) Dihydrotestosterone stimulates proliferation and differentiation of fetal calvarial osteoblasts and dural cells and induces cranial suture fusion. Plast Reconstr Surg 120:1137–1147
Wiren KM, Toombs AR, Semirale AA, Zhang X (2006) Osteoblast and osteocyte apoptosis associated with androgen action in bone, requirement of increased Bax/Bcl-2 ratio. Bone 38:637–651
Garcia AJ, Tom C, Guemes M, Polanco G, Mayorga ME, Wend K, Miranda-Carboni GA, Krum SA (2013) ERα signaling regulates MMP3 expression to induce FasL cleavage and osteoclast apoptosis. J Bone Miner Res 28:283–290
Chen X, Deng Y, Zhou Z, Tao Q, Zhu J, Li X, Chen J, Hou J (2010) 17beta-estradiol combined with testosterone promotes chicken osteoblast proliferation and differentiation by accelerating the cell cycle and inhibiting apoptosis in vitro. Vet Res Commun 34:143–152
Kondoh S, Inoue K, Igarashi K, Sugizaki H, Shirode-Fukuda Y, Inoue E, Yu T, Takeuchi JK, Kanno J, Bonewald LF, Imai Y (2014) Estrogen receptor α in osteocytes regulates trabecular bone formation in female mice. Bone 60:68–77
Gao Y, Huang E, Zhang H, Wang J, Wu N, Chen X, Wang N, Wen S, Nan G, Deng F, Liao Z, Wu D, Zhang B, Zhang J, Haydon RC, Luu HH, Shi LL, He TC (2013) Crosstalk between Wnt/β-catenin and estrogen receptor signaling synergistically promotes osteogenic differentiation of mesenchymal progenitor cells. PLoS One 12:e82436. doi:10.1371/journal.pone.0082436
Börjesson AE, Lagerquist MK, Windahl SH, Ohlsson C (2013) The role of estrogen receptor α in the regulation of bone and growth plate cartilage. Cell Mol Life Sci 70:4023–4037
Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB e Korach KS (1994) Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 331:1056–1061
Morishima A, Grubach MM, Simpson ER, Fischer C, Qin K (1995), Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 80:1841–1845
Carani C, Qin K, Simoni M, faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpsom ER (1997) Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med 337:91–95
Bilezikian JP, Morishima A, Bell J, Grumbach MM (1998) Increase bone mass as a result of estrogentherapy in a man with aromatase deficiency. N Engl J Med 339:599–603
Tenover JS (1992) Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 75:1092–1098
Vermuelen A (1991) Androgens in the aging male. J Clin Endocrinol Metab 73:221–224
Wang C, Swerloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N (2001) Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men. Clin Endocrinol 54:739–750
Leder B (2007) Gonadal steroids and bone metabolism in men. Curr Opin Endocrinol Diabetes Obes 14:241–246
Nuti R, Martini G, Merlotti D, De Paola V, Valleggi F, Gennari L (2007) Bone metabolism in men, role of aromatase activity. J Endocrinol Invest 30(6 Suppl):18–23
Vandenput L, Ohlsson C (2009) Estrogens as regulators of bone health in men. Nat Rev Endocrinol 5:437–443
Vandenput L, Ohlsson C (2010) Sex steroid metabolism in the regulation of bone health in men. J Steroid Biochem Mol Biol 121:582–588
Katznelson L (1998) Therapeutic role of androgens in the treatment of osteoporosis in men. Clin Endocrinol Metab 12:453–470
De Rosa M, Paesano L, Nuzzo V, Zarrilli S, Del Puente A, Oriente P, Lupoli G (2001) Bone mineral density and bone markers in hypogonadotropic and hypergonadotropic hypogonadal men after prolonged testosterone treatment. J Endocrinol Invest 24:246–252
Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK, Zhou XK, Blaho VA, Hla T, Yang P, Kopelovich L, Hudis CA, Dannenberg AJ (2011) Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res 4:329–346
Ghosh S, Hu Y, Li R (2010) Cell density is a critical determinant of aromatase expression in adipose stromal cells. J Steroid Biochem Mol Biol 118:231–236
Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S (2010) The effect of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab 95:3955–3964
Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A (2005) Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol 3:280–293
Nakazawa R, Baba K, Nakano M, Katabami T, Saito N, Takahashi T, Iwamoto T (2006) Hormone profiles after intramuscular injection of testosterone enanthate in patients with hypogonadism. Endocr J 53:305–310
Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S (2000) Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106:1553–1560
Leder BZ, LeBlanc KM, Schoenfeld DA, Eastell R, Finkelstein JS (2003) Differential effects of androgens and estrogens on bone turnover in normal men. J Clin Endocrinol Metab 88:204–210
Duschek EJ, Gooren LJ, Netelenbos C (2004) Effects of raloxifene on gonadotrophins, sex hormones, bone turnover and lipids in healthy elderly men. Eur J Endocrinol 150:539–546
Doran PM, Riggs BL, Atkinson EJ, Khosla S (2001) Effects of raloxifene, a selective estrogen receptor modulator, on bone turnover markers and serum sex steroid and lipid levels in elderly men. J Bone Miner Res 16:2118–2125
Taxel P, Kennedy D, Fall P, Willard A, Shoukri K, Clive J, Raisz LG (2000) The effect of short-term treatment with micronized estradiol on bone turnover and gonadotrophins in older men. Endocr Res 26:381–398
Taxel P, Fall PM, Albertsen PC, Dowsett RD, Trahiotis M, Zimmerman J, Ohannessian C, Raisz LG (2002) The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer. J Clin Endocrinol Metab 87:4907–4913
Masi L, Becherini L, Gennari L, Amedei A, Colli E, Falchetti A, Farci M, Silvestri S, Gonnelli S, Brandi ML (2001) Polymorphism of the aromatase gene in postmenopausal Italian women, distribution and correlation with bone mass and fracture risk. J Clin Endocrinol Metab 86:2263–2269
Salmen T, Heikkinen AM, Mahonen A, Kröger H, Komulainen M, Pallonen H, Saarikoski S, Honkanen R, Mäenpää PH (2003) Relation of aromatase gene polymorphism and hormone replacement therapy to serum estradiol levels, bone mineral density, and fracture risk in early postmenopausal women. Ann Med 35:282–288
Zarrabeitia MT, Hernández JL, Valero C, Zarrabeitia AL, García-Unzueta M, Amado JA, González-Macías J, Riancho JA (2004) A common polymorphism in the 5′-untranslated region of the aromatase gene influences bone mass and fracture risk. Eur J Endocrinol 150:699–704
Conflict of interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Camozzi, V., Bonanni, G., Frigo, A. et al. Effect of a single injection of testosterone enanthate on 17β estradiol and bone turnover markers in hypogonadal male patients. J Endocrinol Invest 38, 389–397 (2015). https://doi.org/10.1007/s40618-014-0183-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-014-0183-5