Current Urology Reports

, 15:417 | Cite as

Alternative Treatment Modalities for the Hypogonadal Patient

Men’s Health (R Carrion and C Yang, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Men’s Health


Testosterone (T) deficiency syndrome (TDS) is a prevalent condition, commonly managed with exogenous T. Despite an abundance of T formulations, alternative treatments are often sought for various reasons. To evaluate outcomes of alternative therapies, a PubMed search was performed of all publications that included men with TDS from 1990 through October 2013, with results summarized. Proposed mechanisms of action were also reviewed to provide a pathophysiologic basis for reported outcomes. Nonpharmacologic therapies that increase endogenous T are weight loss, exercise, and varicocelectomy, while medications used off-label include aromatase inhibitors, human chorionic gonadotropin, and selective estrogen receptor modulators. All reported therapies increase T, while changes in estradiol and adverse events vary by therapeutic class. Although limited data preclude direct comparisons between therapies, exercise and weight loss alone or in combination with medications may be considered first line. The role for surgical therapy in TDS remains undefined and requires further study.


Androgen Testosterone Late-onset Aromatase Human chorionic gonadotropin Selective estrogen receptor modulator Anastrozole Clomiphene Enclomiphene Estradiol Luteinizing hormone Varicocele Varicocelectomy Obesity Body mass index Adverse effects Bone mineral density Osteoporosis Osteopenia Letrozole Testolactone 



Adverse events


Aromatase inhibitors


Body mass index






Estrogen receptor alpha


Estrogen receptor beta


Follicle stimulating hormone


Gonadotropin-releasing hormone


Highly active antiretroviral therapy


Human chorionic gonadotropin


Hypothalamic pituitary gonadal axis




Luteinizing hormone


Placebo controlled


Randomized controlled trial


Selective estrogen receptor blockers




Testosterone deficiency syndrome


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med. 2013;173:1465–6.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Spitzer M, Huang G, Basaria S, Travison TG, Bhasin S. Risks and benefits of testosterone therapy in older men. Nat Rev Endocrinol. 2013;9:414–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Bhasin S, Calof OM, Storer TW, Lee ML, Mazer NA, Jasuja R, et al. Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab. 2006;2:146–59.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, et al. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol. 2005;63:381–94.CrossRefGoogle Scholar
  5. 5.
    Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl. 2011;34:528–40.PubMedCrossRefGoogle Scholar
  6. 6.
    Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;15:289–305.PubMedCrossRefGoogle Scholar
  7. 7.
    Bhasin S, Travison TG, Storer TW, Lakshman K, Kaushik M, Mazer NA, et al. Effect of testosterone supplementation with and without a dual 5alpha-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. JAMA. 2012;307:931–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A: Biol Med Sci. 2005;60:1451–7.CrossRefGoogle Scholar
  9. 9.
    Liu PY, Yee B, Wishart SM, Jimenez M, Jung DG, Grunstein RR, et al. The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. J Clin Endocrinol Metab. 2003;88:3605–13.PubMedCrossRefGoogle Scholar
  10. 10.
    Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR. Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. J Androl. 2003;24:299–311.PubMedGoogle Scholar
  11. 11.
    Grimes DA, Lopez LM, Gallo MF, Halpern V, Nanda K, Schulz KF. Steroid hormones for contraception in men. Cochrane Database Syst Rev. 2012;3, CD004316.PubMedGoogle Scholar
  12. 12.
    Boregowda K, Joels L, Stephens JW, Price DE. Persistent primary hypogonadism associated with anabolic steroid abuse. Fertil Steril. 2011;96:e7–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Schnorr JA, Bray MJ, Veldhuis JD. Aromatization mediates testosterone’s short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men. J Clin Endocrinol Metab. 2001;86:2600–6.PubMedGoogle Scholar
  14. 14.
    Hayes FJ, DeCruz S, Seminara SB, Boepple PA, Crowley Jr WF. Differential regulation of gonadotropin secretion by testosterone in the human male: absence of a negative feedback effect of testosterone on follicle-stimulating hormone secretion. J Clin Endocrinol Metab. 2001;86:53–8.PubMedGoogle Scholar
  15. 15.
    Trost LW, Serefoglu E, Gokce A, Linder BJ, Sartor AO, Hellstrom WJ. Androgen deprivation therapy impact on quality of life and cardiovascular health, monitoring therapeutic replacement. J Sex Med. 2013;10 Suppl 1:84–101.PubMedCrossRefGoogle Scholar
  16. 16.
    Vermeulen A, Kaufman JM, Giagulli VA. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metab. 1996;81:1821–6.PubMedGoogle Scholar
  17. 17.••
    Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011–22. DB, PC, RCT, variable dose trial of T versus T with anastrozole. Results demonstrated significantly higher body fat and reduced muscle at highest dose of T with anastrozole. Also demonstrated improved outcomes in sexual desire and function with T alone compared to combined therapy.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Filippi S, Luconi M, Granchi S, Vignozzi L, Bettuzzi S, Tozzi P, et al. Estrogens, but not androgens, regulate expression and functional activity of oxytocin receptor in rabbit epididymis. Endocrinology. 2002;143:4271–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Vignozzi L, Filippi S, Luconi M, Morelli A, Mancina R, Marini M, et al. Oxytocin receptor is expressed in the penis and mediates an estrogen-dependent smooth muscle contractility. Endocrinology. 2004;145:1823–34.PubMedCrossRefGoogle Scholar
  20. 20.
    Van Pottelbergh I, Braeckman L, De Bacquer D, De Backer G, Kaufman JM. Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men. Atherosclerosis. 2003;166:95–102.PubMedCrossRefGoogle Scholar
  21. 21.
    Caulin-Glaser T, Garcia-Cardena G, Sarrel P, Sessa WC, Bender JR. 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circ Res. 1997;81:885–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Rochira V, Madeo B, Zirilli L, Caffagni G, Maffei L, Carani C. Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men. Diabet Med J Br Diabet Assoc. 2007;24:1491–5.CrossRefGoogle Scholar
  23. 23.
    Maffei L, Murata Y, Rochira V, Tubert G, Aranda C, Vazquez M, et al. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment. J Clin Endocrinol Metab. 2004;89:61–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Rochira V, Zirilli L, Madeo B, Maffei L, Carani C. Testosterone action on erythropoiesis does not require its aromatization to estrogen: insights from the testosterone and estrogen treatment of two aromatase-deficient men. J Steroid Biochem Mol Biol. 2009;113:189–94.PubMedCrossRefGoogle Scholar
  25. 25.
    Rhoden EL, Morgentaler A. Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole. Int J Impot Res. 2004;16:95–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Khosla S, Melton 3rd LJ, Atkinson EJ, O’Fallon WM. Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab. 2001;86:3555–61.PubMedCrossRefGoogle Scholar
  27. 27.
    Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest. 2000;106:1553–60.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Piccolella M, Crippa V, Messi E, Tetel MJ, Poletti A. Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells. Pharmacol Res Off J Ital Pharmacol Soc. 2014;79:13–20.Google Scholar
  29. 29.
    Kumar R, Verma V, Sarswat A, Maikhuri JP, Jain A, Jain RK, et al. Selective estrogen receptor modulators regulate stromal proliferation in human benign prostatic hyperplasia by multiple beneficial mechanisms–action of two new agents. Investig New Drugs. 2012;30:582–93.CrossRefGoogle Scholar
  30. 30.
    Amory JK, Wang C, Swerdloff RS, Anawalt BD, Matsumoto AM, Bremner WJ, et al. The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J Clin Endocrinol Metab. 2007;92:1659–65.PubMedCrossRefGoogle Scholar
  31. 31.
    Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci U S A. 1993;90:11162–6.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Toda K, Okada T, Takeda K, Akira S, Saibara T, Shiraishi M, et al. Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17beta-oestradiol to aromatase gene (Cyp19) knockout mice. J Endocrinol. 2001;168:455–63.PubMedCrossRefGoogle Scholar
  33. 33.•
    Allan CM, Couse JF, Simanainen U, Spaliviero J, Jimenez M, Rodriguez K, et al. Estradiol induction of spermatogenesis is mediated via an estrogen receptor-{alpha} mechanism involving neuroendocrine activation of follicle-stimulating hormone secretion. Endocrinology. 2010;151:2800–10. Important manuscript describing role of ER-α in maintaining spermatogenesis. This likely accounts for improvements and/or maintenance of spermatogenesis achieved with SERMs.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Lardone MC, Castillo P, Valdevenito R, Ebensperger M, Ronco AM, Pommer R, et al. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure. Int J Androl. 2010;33:650–60.PubMedGoogle Scholar
  35. 35.
    Lima N, Cavaliere H, Knobel M, Halpern A, Medeiros-Neto G. Decreased androgen levels in massively obese men may be associated with impaired function of the gonadostat. Int J Obes Relat Metab Disord J Int Assoc Study Obes. 2000;24:1433–7.CrossRefGoogle Scholar
  36. 36.
    Pastuszak AW, Mittakanti H, Liu JS, Gomez L, Lipshultz LI, Khera M. Pharmacokinetic evaluation and dosing of subcutaneous testosterone pellets. J Androl. 2012;33:927–37.PubMedCrossRefGoogle Scholar
  37. 37.
    Hammoud A, Gibson M, Hunt SC, Adams TD, Carrell DT, Kolotkin RL, et al. Effect of Roux-en-Y gastric bypass surgery on the sex steroids and quality of life in obese men. J Clin Endocrinol Metab. 2009;94:1329–32.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.••
    Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol Eur Fed Endocr Soc. 2013;168:829–43. Systematic review and meta-analysis of trials evaluating the impact of weight loss on T.CrossRefGoogle Scholar
  39. 39.
    Khoo J, Tian HH, Tan B, Chew K, Ng CS, Leong D, et al. Comparing effects of low- and high-volume moderate-intensity exercise on sexual function and testosterone in obese men. J Sex Med. 2013;10:1823–32.PubMedCrossRefGoogle Scholar
  40. 40.
    Cadore EL, Lhullier FL, Alberton CL, Almeida AP, Sapata KB, Korzenowski AL, et al. Salivary hormonal responses to different water-based exercise protocols in young and elderly men. J Strength Cond Res Natl Strength Cond Assoc. 2009;23:2695–701.CrossRefGoogle Scholar
  41. 41.
    Cadore EL, Lhullier FL, Brentano MA, da Silva EM, Ambrosini MB, Spinelli R, et al. Hormonal responses to resistance exercise in long-term trained and untrained middle-aged men. J Strength Cond Res Natl Strength Cond Assoc. 2008;22:1617–24.CrossRefGoogle Scholar
  42. 42.
    Ahtiainen JP, Pakarinen A, Kraemer WJ, Hakkinen K. Acute hormonal responses to heavy resistance exercise in strength athletes versus nonathletes. Can J Appl Physiol Rev Can Physiol Appl. 2004;29:527–43.CrossRefGoogle Scholar
  43. 43.
    Hough J, Corney R, Kouris A, Gleeson M. Salivary cortisol and testosterone responses to high-intensity cycling before and after an 11-day intensified training period. J Sports Sci. 2013;31:1614–23.PubMedCrossRefGoogle Scholar
  44. 44.
    Wahl P, Mathes S, Kohler K, Achtzehn S, Bloch W, Mester J. Acute metabolic, hormonal, and psychological responses to different endurance training protocols. Horm Metab Res Hor Stoffwechs Horm Metab. 2013;45:827–33.CrossRefGoogle Scholar
  45. 45.
    Su LM, Goldstein M, Schlegel PN. The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles. J Urol. 1995;154:1752–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Cayan S, Kadioglu A, Orhan I, Kandirali E, Tefekli A, Tellaloglu S. The effect of microsurgical varicocelectomy on serum follicle stimulating hormone, testosterone and free testosterone levels in infertile men with varicocele. BJU Int. 1999;84:1046–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Sathya Srini V, Belur Veerachari S. Does varicocelectomy improve gonadal function in men with hypogonadism and infertility? Analysis of a prospective study. Int J Endocrinol. 2011;2011:916380.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Zohdy W, Ghazi S, Arafa M. Impact of varicocelectomy on gonadal and erectile functions in men with hypogonadism and infertility. J Sex Med. 2011;8:885–93.PubMedCrossRefGoogle Scholar
  49. 49.
    Hsiao W, Rosoff JS, Pale JR, Powell JL, Goldstein M. Varicocelectomy is associated with increases in serum testosterone independent of clinical grade. Urology. 2013;81:1213–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Hsiao W, Rosoff JS, Pale JR, Greenwood EA, Goldstein M. Older age is associated with similar improvements in semen parameters and testosterone after subinguinal microsurgical varicocelectomy. J Urol. 2011;185:620–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Younes AK. Improvement of sexual activity, pregnancy rate, and low plasma testosterone after bilateral varicocelectomy in impotence and male infertility patients. Arch Androl. 2003;49:219–28.PubMedGoogle Scholar
  52. 52.
    Tanrikut C, Goldstein M, Rosoff JS, Lee RK, Nelson CJ, Mulhall JP. Varicocele as a risk factor for androgen deficiency and effect of repair. BJU Int. 2011;108:1480–4.PubMedCrossRefGoogle Scholar
  53. 53.
    Burnett-Bowie SA, Roupenian KC, Dere ME, Lee H, Leder BZ. Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol. 2008;70:116–23.CrossRefGoogle Scholar
  54. 54.
    Dougherty RH, Rohrer JL, Hayden D, Rubin SD, Leder BZ. Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels. Clin Endocrinol. 2005;62:228–35.CrossRefGoogle Scholar
  55. 55.
    Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C. Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. J Clin Endocrinol Metab. 2004;89:1174–80.PubMedCrossRefGoogle Scholar
  56. 56.
    Leder BZ, Finkelstein JS. Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men. Osteoporos Int. 2005;16:1487–94.PubMedCrossRefGoogle Scholar
  57. 57.
    Holbrook JM, Cohen PG. Aromatase inhibition for the treatment of idiopathic hypogonadotropic hypogonadism in men with premature ejaculation. South Med J. 2003;96:544–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Loves S, Ruinemans-Koerts J, de Boer H. Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol Eur Fed Endocr Soc. 2008;158:741–7.CrossRefGoogle Scholar
  59. 59.
    de Boer H, Verschoor L, Ruinemans-Koerts J, Jansen M. Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism. Diabetes Obes Metab. 2005;7:211–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Zumoff B, Miller LK, Strain GW. Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone. Metab Clin Exp. 2003;52:1126–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Burnett-Bowie SA, McKay EA, Lee H, Leder BZ. Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels. J Clin Endocrinol Metab. 2009;94:4785–92.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Tsujimura A, Matsumiya K, Miyagawa Y, Takao T, Fujita K, Takada S, et al. Comparative study on evaluation methods for serum testosterone level for PADAM diagnosis. Int J Impot Res. 2005;17:259–63.PubMedCrossRefGoogle Scholar
  63. 63.••
    Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol. 2013;189:647–50. Treated men undergoing T therapy with HCG with resultant preserved spermatogenesis.PubMedCrossRefGoogle Scholar
  64. 64.
    Anderson RA, Wu FC. Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate. J Clin Endocrinol Metab. 1996;81:896–901.PubMedGoogle Scholar
  65. 65.
    FDA. Human chorionic gonadotropin adverse effects. 2013.Google Scholar
  66. 66.
    Kurosawa T, Hiroi H, Momoeda M, Inoue S, Taketani Y. Clomiphene citrate elicits estrogen agonistic/antagonistic effects differentially via estrogen receptors alpha and beta. Endocr J. 2010;57:517–21.PubMedCrossRefGoogle Scholar
  67. 67.
    Chua ME, Escusa KG, Luna S, Tapia LC, Dofitas B, Morales M. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology. 2013;1:749–57.PubMedCrossRefGoogle Scholar
  68. 68.
    Tenover JS, Bremner WJ. The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men. J Androl. 1991;12:258–63.PubMedGoogle Scholar
  69. 69.
    Guay AT, Bansal S, Heatley GJ. Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo-controlled trial with clomiphene citrate. J Clin Endocrinol Metab. 1995;80:3546–52.PubMedGoogle Scholar
  70. 70.
    Guay AT, Jacobson J, Perez JB, Hodge MB, Velasquez E. Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit? Int J Impot Res. 2003;15:156–65.PubMedCrossRefGoogle Scholar
  71. 71.•
    Da Ros CT, Averbeck MA. Twenty-five milligrams of clomiphene citrate presents positive effect on treatment of male testosterone deficiency—a prospective study. Int Braz J Urol Off J Braz Soc Urol. 2012;38:512–8. Largest prospective trial of clomiphene citrate alone. Demonstrated improve quality of life without improvemen in lipids or fasting glucose levels.CrossRefGoogle Scholar
  72. 72.
    Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012;110:573–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012;110:1524–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Shabsigh A, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, et al. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med. 2005;2:716–21.PubMedCrossRefGoogle Scholar
  75. 75.
    Shand B, Gilchrist N, Blackwell T, March R. The hemorheological effects of raloxifene in postmenopausal women with osteoporosis. Results of a 3-year placebo-controlled clinical trial. Clin Hemorheol Microcirc. 2002;26:249–55.PubMedGoogle Scholar
  76. 76.•
    Mechlin CW, Frankel J, McCullough A. Coadministration of anastrozole sustains therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion. J Sex Med. 2014;11:254–61. Retrospective analysis of T with anastrozole. Demonstrated improved duration of therapeutic T levels with the addition of anastrozole.PubMedCrossRefGoogle Scholar
  77. 77.
    Herzog AG, Farina EL, Drislane FW, Schomer DL, Smithson SD, Fowler KM, et al. A comparison of anastrozole and testosterone versus placebo and testosterone for treatment of sexual dysfunction in men with epilepsy and hypogonadism. Epilepsy Behav. 2010;17:264–71.PubMedCrossRefGoogle Scholar
  78. 78.
    Young LA, Neiss MB, Samuels MH, Roselli CE, Janowsky JS. Cognition is not modified by large but temporary changes in sex hormones in men. J Clin Endocrinol Metab. 2010;95:280–8.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Herzog AG, Klein P, Jacobs AR. Testosterone versus testosterone and testolactone in treating reproductive and sexual dysfunction in men with epilepsy and hypogonadism. Neurology. 1998;50:782–4.PubMedCrossRefGoogle Scholar
  80. 80.
    Richardson D, Goldmeier D, Frize G, Lamba H, De Souza C, Kocsis A, et al. Letrozole versus testosterone. a single-center pilot study of HIV-infected men who have sex with men on highly active anti-retroviral therapy (HAART) with hypoactive sexual desire disorder and raised estradiol levels. J Sex Med. 2007;4:502–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Rolf C, von Eckardstein S, Koken U, Nieschlag E. Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study. Eur J Endocrinol Eur Fed Endocr Soc. 2002;146:505–11.CrossRefGoogle Scholar
  82. 82.
    Takao T, Tsujimura A, Nakayama J, Matsuoka Y, Miyagawa Y, Takada S, et al. Lower urinary tract symptoms after hormone replacement therapy in Japanese patients with late-onset hypogonadism: a preliminary report. Int J Urol Off J Japan Urol Assoc. 2009;16:212–4.Google Scholar
  83. 83.•
    Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost. J Sex Med. 2010;7:269–76. Demonstrated improved cost effectiveness of clomiphene citrate over topical T therapies with equivalent efficacy.PubMedCrossRefGoogle Scholar
  84. 84.
    Kaminetsky J, Werner M, Fontenot G, Wiehle RD. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. J Sex Med. 2013;10:1628–35.PubMedCrossRefGoogle Scholar
  85. 85.
    Wiehle R, Cunningham GR, Pitteloud N, Wike J, Hsu K, Fontenot GK, et al. Testosterone restoration by enclomiphene citrate in men with secondary hypogonadism: pharmacodynamics and pharmacokinetics. BJU Int. 2013. SB, RCT, variable dose study of enclomiphene versus T. Results demonstrated similar improvements in T (at 25 mg dose of enclomiphene) with more consistently maintained therapeutic levels among those receiving enclomiphene.Google Scholar
  86. 86.
    Steinberger E, Ayala C, Hsi B, Smith KD, Rodriguez-Rigau LJ, Weidman ER, et al. Utilization of commercial laboratory results in management of hyperandrogenism in women. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinologist. 1998;4:1–10.Google Scholar
  87. 87.
    Brambilla DJ, O’Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol. 2007;67:853–62.CrossRefGoogle Scholar
  88. 88.
    Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536–59.PubMedCrossRefGoogle Scholar
  89. 89.
    Brambilla DJ, Matsumoto AM, Araujo AB, McKinlay JB. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab. 2009;94:907–13.PubMedCentralPubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Mayo ClinicRochesterUSA
  2. 2.Baylor College of MedicineHoustonUSA
  3. 3.Baylor ClinicHoustonUSA

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