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Chapter 12 - Endocrine Causes of Male Infertility – Diagnosis and Treatment

from Section 2 - Clinical Evaluation of the Infertile Male

Published online by Cambridge University Press:  08 July 2023

Larry I. Lipshultz
Affiliation:
Baylor College of Medicine, Texas
Stuart S. Howards
Affiliation:
University of Virginia
Craig S. Niederberger
Affiliation:
University of Illinois, Chicago
Dolores J. Lamb
Affiliation:
Weill Cornell Medical College, New York
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Summary

Infertility is generally defined as the inability to achieve conception after 12 months of regular unprotected sexual intercourse (World Health Organization (WHO)) [1]. It is estimated that approximately one-third of infertility cases are due to male factor infertility, another one-third due to female factor infertility, and the remainder due to combined male and female factors or unexplained cause(s). A recent large cross-sectional study suggests that about 10.1 percent of men experience infertility [2], and in a birth cohort study, in men aged 38 years, male infertility ranged from 14.4 to 21.8 percent [3]. Endocrine causes of male infertility are surprisingly infrequent, given that fertility is dependent on an intact hypothalamic–pituitary–testicular (HPT) axis (see Chapter 4) for adequate spermatogenesis. Systemic endocrine diseases and disturbances of the HPT axis comprise approximately 2 to 5 percent of causes of male infertility [4, 5]. Though uncommon, endocrine causes of infertility are important to diagnose, as specific treatment is available in most cases to ameliorate the clinical symptoms of hypogonadism and, in some instances, for treatment of infertility. Understanding the underlying endocrine etiology of infertility allows for shared decision-making in the management of a couple with infertility; furthermore, certain conditions may have serious health consequences if left untreated. Evaluation of endocrine causes is essential when investigating male factor infertility.

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Publisher: Cambridge University Press
Print publication year: 2023

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References

Further Reading

Barratt, CLR, Bjorndahl, L, De Jonge, CJ, et al. The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities. Hum Reprod Update 2017;23:660–80.Google Scholar
Bhasin, S, Brito, JP, Cunningham, GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2018;103:1715–44.CrossRefGoogle ScholarPubMed
Dwyer, AA, Raivio, T, Pitteloud, N. Gonadotrophin replacement for induction of fertility in hypogonadal men. Best Pract Res Clin Endocrinol Metab 2015;29:91103.CrossRefGoogle ScholarPubMed
Nieschlag, E, Ferlin, A, Gravholt, CH, et al. The Klinefelter syndrome: current management and research challenges. Andrology 2016;4:545–9.Google Scholar
Stamou, MI, Georgopoulos, NA. Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metabolism 2018;86:124–34.Google Scholar

References

Barratt, CLR, Bjorndahl, L, De Jonge, CJ, et al. The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance-challenges and future research opportunities. Hum Reprod Update 2017;23:660–80.CrossRefGoogle ScholarPubMed
Datta, J, Palmer, MJ, Tanton, C, et al. Prevalence of infertility and help seeking among 15 000 women and men. Hum Reprod 2016;31:2108–18.CrossRefGoogle ScholarPubMed
van Roode, T, Dickson, NP, Righarts, AA, Gillett, WR. Cumulative incidence of infertility in a New Zealand birth cohort to age 38 by sex and the relationship with family formation. Fertil Steril 2015;103:10538.e2.CrossRefGoogle Scholar
Jarow, JP. Endocrine causes of male infertility. Urol Clin North Am 2003;30:8390.Google Scholar
Snyder, PJ. Hypogonadotropic hypogonadism: gonadotropin therapy. Curr Ther Endocrinol Metab 1994;5:300–3.Google Scholar
Moore, AM, Coolen, LM, Porter, DT, Goodman, RL, Lehman, MN. KNDy cells revisited. Endocrinology 2018;159:3219–34.CrossRefGoogle ScholarPubMed
Stamou, MI, Georgopoulos, NA. Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metabolism 2018;86:124–34.Google Scholar
Stamatiades, GA, Kaiser, UB. Gonadotropin regulation by pulsatile GnRH: signaling and gene expression. Mol Cell Endocrinol 2018;463:131–41.Google Scholar
de Kretser, DM, Buzzard, JJ, Okuma, Y, et al. The role of activin, follistatin and inhibin in testicular physiology. Mol Cell Endocrinol 2004;225:5764.Google Scholar
Namwanje, M, Brown, CW. Activins and inhibins: roles in development, physiology, and disease. Cold Spring Harb Perspect Biol 2016;8:a021881.CrossRefGoogle ScholarPubMed
Page, ST. Physiologic role and regulation of intratesticular sex steroids. Curr Opin Endocrinol Diabetes Obes 2011;18:217–23.CrossRefGoogle ScholarPubMed
Coviello, AD, Bremner, WJ, Matsumoto, AM, et al. Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen. J Androl 2004;25:931–8.CrossRefGoogle Scholar
Wang, C, Festin, MP, Swerdloff, RS. Male hormonal contraception: where are we now? Curr Obstet Gynecol Rep 2016;5:3847.CrossRefGoogle ScholarPubMed
Wang, C, Swerdloff, RS. Hormonal approaches to male contraception. Curr Opin Urol 2010;20:520–4.Google Scholar
Wilson, JD. Androgen abuse by athletes. Endocr Rev 1988;9:181–99.CrossRefGoogle ScholarPubMed
Handelsman, DJ. Testosterone: use, misuse and abuse. Med J Aust 2006;185:436–9.Google Scholar
Horton, R. Sex steroid production and secretion in the male. Andrologia 1978;10:183–94.Google Scholar
Horton, R, Shinsako, J, Forsham, PH. Testosterone production and metabolic clearance rates with volumes of distribution in normal adult men and women. Acta Endocrinol (Copenh) 1965;48:446–58.Google Scholar
Carreau, S, Wolczynski, S, Galeraud-Denis, I. Aromatase, oestrogens and human male reproduction. Philos Trans R Soc Lond B Biol Sci 2010;365:1571–9.Google Scholar
Carreau, S, Bouraima-Lelong, H, Delalande, C. Role of estrogens in spermatogenesis. Front Biosci (Elite edition) 2012;4:111.CrossRefGoogle ScholarPubMed
Muttukrishna, S, Yussoff, H, Naidu, M, et al. Serum anti-Mullerian hormone and inhibin B in disorders of spermatogenesis. Fertil Steril 2007;88:516–18.Google Scholar
Andersen, JM, Herning, H, Witczak, O, Haugen, TB. Anti-Mullerian hormone in seminal plasma and serum: association with sperm count and sperm motility. Hum Reprod 2016;31:1662–7.Google Scholar
Toulis, KA, Iliadou, PK, Venetis, CA, et al. Inhibin B and anti-Mullerian hormone as markers of persistent spermatogenesis in men with non-obstructive azoospermia: a meta-analysis of diagnostic accuracy studies. Hum Reprod Update 2010;16:713–24.Google Scholar
Bhasin, S, Brito, JP, Cunningham, GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2018;103:1715–44.Google Scholar
Ottesen, AM, Aksglaede, L, Garn, I, et al. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy. Am J Med Genet A 2010;152A:1206–12.Google Scholar
Griffin, JE, Punyashthiti, K, Wilson, JD. Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance. J Clin Invest 1976;57:1342–51.CrossRefGoogle ScholarPubMed
Imperato-McGinley, J, Guerrero, L, Gautier, T, Peterson, RE. Steroid 5 alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974;186:1213–15.CrossRefGoogle Scholar
Imperato-McGinley, J, Peterson, RE. Male pseudohermaphroditism: the complexities of male phenotypic development. Am J Med 1976;61:251–72.Google Scholar
Imperato-McGinley, J, Zhu, YS. Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol 2002;198:51–9.Google Scholar
Auchus, RJ. Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. J Steroid Biochem Mol Biol 2017;165:71–8.CrossRefGoogle ScholarPubMed
McPhaul, MJ, Marcelli, M, Zoppi, S, Griffin, JE, Wilson, JD. Genetic basis of endocrine disease. 4. The spectrum of mutations in the androgen receptor gene that causes androgen resistance. J Clin Endocrinol Metab 1993;76:1723.Google Scholar
Boehm, U, Bouloux, PM, Dattani, MT, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 2015;11:547–64.Google Scholar
Hatipoglu, N, Kurtoglu, S. Micropenis: etiology, diagnosis and treatment approaches. J Clin Res Pediatr Endocrinol 2013;5:217–23.Google Scholar
Tsang, S. When size matters: a clinical review of pathological micropenis. J Pediatr Health Care 2010;24:231–40.CrossRefGoogle ScholarPubMed
Prader, A. Testicular size: assessment and clinical importance. Triangle 1966;7:240–53.Google Scholar
Marshall, WA, Tanner, JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:1323.Google Scholar
Tanner, JM, Whitehouse, RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51:170–9.Google Scholar
Wang, C, Swerdloff, RS. Limitations of semen analysis as a test of male fertility and anticipated needs from newer tests. Fertil Steril 2014;102:1502–7.Google Scholar
Collomp, K, Baillot, A, Forget, H, Coquerel, A, Rieth, N, Vibarel-Rebot, N. Altered diurnal pattern of steroid hormones in relation to various behaviors, external factors and pathologies: a review. Physiol Behav 2016;164:6885.CrossRefGoogle ScholarPubMed
Bremner, WJ, Vitiello, MV, Prinz, PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab 1983;56:1278–81.Google Scholar
Diver, MJ, Imtiaz, KE, Ahmad, AM, Vora, JP, Fraser, WD. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol (Oxf) 2003;58:710–17.Google Scholar
Taieb, J, Mathian, B, Millot, F, et al. Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography-mass spectrometry in sera from 116 men, women, and children. Clin Chem 2003;49:1381–95.Google Scholar
Wang, C, Catlin, DH, Demers, LM, Starcevic, B, Swerdloff, RS. Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 2004;89:534–43.Google Scholar
Rosner, W, Auchus, RJ, Azziz, R, Sluss, PM, Raff, H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007;92:405–13.CrossRefGoogle ScholarPubMed
Rosner, W, Vesper, H. Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab 2010;95:4542–8.CrossRefGoogle ScholarPubMed
Vesper, HW, Botelho, JC. Standardization of testosterone measurements in humans. J Steroid Biochem Mol Biol 2010;121:513–19.Google Scholar
Vesper, HW, Botelho, JC, Shacklady, C, Smith, A, Myers, GL. CDC project on standardizing steroid hormone measurements. Steroids 2008;73:1286–92.Google Scholar
Travison, TG, Vesper, HW, Orwoll, E, et al. Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the United States and Europe. J Clin Endocrinol Metab 2017;102:1161–73.CrossRefGoogle ScholarPubMed
Wu, FC, Tajar, A, Beynon, JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010;363:123–35.Google Scholar
Ohlsson, C, Wallaschofski, H, Lunetta, KL, et al. Genetic determinants of serum testosterone concentrations in men. PLoS Genet 2011;7:e1002313.Google Scholar
Snyder, PJ, Rudenstein, RS, Gardner, DF, Rothman, JG. Repetitive infusion of gonadotropin-releasing hormone distinguishes hypothalamic from pituitary hypogonadism. J Clin Endocrinol Metab 1979;48:864–8.CrossRefGoogle ScholarPubMed
Bhasin, S, Ellenberg, SS, Storer, TW, et al. Effect of testosterone replacement on measures of mobility in older men with mobility limitation and low testosterone concentrations: secondary analyses of the Testosterone Trials. Lancet Diab Endocrinol 2018;6:879–90.Google Scholar
Wu, FC, Tajar, A, Pye, SR, et al. Hypothalamic–pituitary–testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 2008;93:2737–45.Google Scholar
Krausz, C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab 2011;25:271–85.Google Scholar
Aksglaede, L, Link, K, Giwercman, A, Jorgensen, N, Skakkebaek, NE, Juul, A. 47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management. Am J Med Genetics C Semin Medical Genetics 2013;163C:5563.Google Scholar
Aiman, J, Griffin, JE, Gazak, JM, Wilson, JD, MacDonald, PC. Androgen insensitivity as a cause of infertility in otherwise normal men. N Engl J Med 1979;300:223–7.Google Scholar
Basaria, S. Androgen abuse in athletes: detection and consequences. J Clin Endocrinol Metab 2010;95:1533–43.Google Scholar
Lanfranco, F, Kamischke, A, Zitzmann, M, Nieschlag, E. Klinefelter’s syndrome. Lancet 2004;364:273–83.Google Scholar
Simpson, JL, de la Cruz, F, Swerdloff, RS, et al. Klinefelter syndrome: expanding the phenotype and identifying new research directions. Genet Med 2003;5:460–8.CrossRefGoogle ScholarPubMed
Bojesen, A, Juul, S, Gravholt, CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 2003;88:622–6.Google Scholar
Niewoehner, CB, Nuttal, FQ. Gynecomastia in a hospitalized male population. Am J Med 1984;77:633–8.Google Scholar
Rohayem, J, Nieschlag, E, Zitzmann, M, Kliesch, S. Testicular function during puberty and young adulthood in patients with Klinefelter’s syndrome with and without spermatozoa in seminal fluid. Andrology 2016;4:1178–86.CrossRefGoogle Scholar
Wikstrom, AM, Dunkel, L, Wickman, S, Norjavaara, E, Ankarberg-Lindgren, C, Raivio, T. Are adolescent boys with Klinefelter syndrome androgen deficient? A longitudinal study of Finnish 47,XXY boys. Pediatr Res 2006;59:854–9.Google Scholar
Dunkel, L, Siimes, MA, Bremner, WJ. Reduced inhibin and elevated gonadotropin levels in early pubertal boys with testicular defects. Pediatr Res 1993;33:514–18.Google Scholar
Wikstrom, AM, Dunkel, L. Klinefelter syndrome. Best Pract Res Clin Endocrinol Metab 2011;25:239–50.Google Scholar
Wikstrom, AM, Raivio, T, Hadziselimovic, F, Wikstrom, S, Tuuri, T, Dunkel, L. Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion. J Clin Endocrinol Metab 2004;89:2263–70.Google Scholar
Aksglaede, L, Wikstrom, AM, Rajpert-De Meyts, E, Dunkel, L, Skakkebaek, NE, Juul, A. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update 2006;12:3948.Google Scholar
Bojesen, A, Host, C, Gravholt, CH. Klinefelter’s syndrome, type 2 diabetes and the metabolic syndrome: the impact of body composition. Mol Hum Reprod 2010;16:396401.Google Scholar
Kanakis, GA, Nieschlag, E. Klinefelter syndrome: more than hypogonadism. Metabolism 2018;86:135–44.Google Scholar
Bojesen, A, Birkebaek, N, Kristensen, K, et al. Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone. Osteoporos Int 2011;22:1441–50.Google Scholar
Bojesen, A, Gravholt, CH. Klinefelter syndrome in clinical practice. Nat Clin Pract Urol 2007;4:192204.Google Scholar
Bojesen, A, Kristensen, K, Birkebaek, NH, et al. The metabolic syndrome is frequent in Klinefelter’s syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 2006;29:1591–8.Google Scholar
Nieschlag, E, Ferlin, A, Gravholt, CH, et al. The Klinefelter syndrome: current management and research challenges. Andrology 2016;4:545–9.Google Scholar
Schlegel, PN, Palermo, GD, Goldstein, M, et al. Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia. Urology 1997;49:435–40.Google Scholar
Tuttelmann, F, Werny, F, Cooper, TG, Kliesch, S, Simoni, M, Nieschlag, E. Clinical experience with azoospermia: aetiology and chances for spermatozoa detection upon biopsy. Int J Androl 2011;34:291–8.Google Scholar
Corona, G, Pizzocaro, A, Lanfranco, F, et al. Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update 2017;23:265–75.Google Scholar
Ramasamy, R, Ricci, JA, Palermo, GD, Gosden, LV, Rosenwaks, Z, Schlegel, PN. Successful fertility treatment for Klinefelter’s syndrome. J Urol 2009;182:1108–13.Google Scholar
Ohlander, SJ, Lindgren, MC, Lipshultz, LI. Testosterone and Male Infertility. Urol Clin North Am 2016;43:195202.Google Scholar
Carreau, S, Bouraima-Lelong, H, Delalande, C. Estrogen, a female hormone involved in spermatogenesis. Adv Med Sci 2012;57:31–6.Google Scholar
Raman, JD, Schlegel, PN. Aromatase inhibitors for male infertility. J Urol 2002;167:624–9.Google Scholar
Schlegel, PN. Aromatase inhibitors for male infertility. Fertil Steril 2012;98:1359–62.CrossRefGoogle ScholarPubMed
Fawzy, F, Hussein, A, Eid, MM, El Kashash, AM, Salem, HK. Cryptorchidism and fertility. Clin Med Insights Reprod Health 2015;9:3943.CrossRefGoogle ScholarPubMed
Virtanen, HE, Toppari, J. Cryptorchidism and fertility. Endocrinol Metab Clin North Am 2015;44:751–60.Google Scholar
Ghirri, P, Ciulli, C, Vuerich, M, et al. Incidence at birth and natural history of cryptorchidism: a study of 10,730 consecutive male infants. J Endocrinol Invest 2002;25:709–15.Google Scholar
Virtanen, HE, Toppari, J. Epidemiology and pathogenesis of cryptorchidism. Hum Reprod Update 2008;14:4958.Google Scholar
Virtanen, HE, Bjerknes, R, Cortes, D, et al. Cryptorchidism: classification, prevalence and long-term consequences. Acta Paediatr 2007;96:611–16.Google Scholar
Lane, C, Boxall, J, MacLellan, D, Anderson, PA, Dodds, L, Romao, RLP. A population-based study of prevalence trends and geospatial analysis of hypospadias and cryptorchidism compared with non-endocrine mediated congenital anomalies. J Pediatr Urol 2017;13:284.e1–7.Google Scholar
Gore, AC, Chappell, VA, Fenton, SE, et al. EDC-2: The Endocrine Society’s Second Scientific Statement on endocrine-disrupting chemicals. Endocr Rev 2015;36:E1150.Google Scholar
Kolon, TF, Herndon, CD, Baker, LA, et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol 2014;192:337–45.Google Scholar
Yong, EL, Loy, CJ, Sim, KS. Androgen receptor gene and male infertility. Hum Reprod 2003;9:17.Google Scholar
Wilson, JD, Harrod, MJ, Goldstein, JL, Hemsell, DL, MacDonald, PC. Familial incomplete male pseudohermaphroditism, type 1. Evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome. N Engl J Med 1974;290:1097–103.Google Scholar
Griffin, JE, Leshin, M, Wilson, JD. Androgen resistance syndromes. Am J Physiol 1982;243:E81–7.Google ScholarPubMed
Hiort, O, Holterhus, PM. Androgen insensitivity and male infertility. Int J Androl 2003;26:1620.Google Scholar
Ferlin, A, Bartoloni, L, Rizzo, G, Roverato, A, Garolla, A, Foresta, C. Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility. Mol Hum Reprod 2004;10:417–21.CrossRefGoogle ScholarPubMed
Casella, R, Maduro, MR, Misfud, A, Lipshultz, LI, Yong, EL, Lamb, DJ. Androgen receptor gene polyglutamine length is associated with testicular histology in infertile patients. J Urol 2003;169:224–7.Google Scholar
Rochira, V, Balestrieri, A, Madeo, B, et al. Congenital estrogen deficiency: in search of the estrogen role in human male reproduction. Mol Cell Endocrinol 2001;178:107–15.Google Scholar
Hamilton, KJ, Hewitt, SC, Arao, Y, Korach, KS. Estrogen hormone biology. Curr Top Dev Biol 2017;125:109–46.Google Scholar
Simpson, ER. Genetic mutations resulting in estrogen insufficiency in the male. Mol Cell Endocrinol 1998;145:55–9.Google Scholar
Bulun, SE. Aromatase and estrogen receptor alpha deficiency. Fertil Steril 2014;101:323–9.Google Scholar
Smith, EP, Boyd, J, Frank, GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man [see comments] [published erratum appears in N Engl J Med 1995;332:131]. N Engl J Med 1994;331:1056–61.Google Scholar
Aschim, EL, Giwercman, A, Stahl, O, et al. The RsaI polymorphism in the estrogen receptor-beta gene is associated with male infertility. J Clin Endocrinol Metab 2005;90:5343–8.Google Scholar
Bordin, BM, Moura, KK. Association between RsaI polymorphism in estrogen receptor beta gene and male infertility. Genet Mol Res 2015;14:10954–60.Google Scholar
Safarinejad, MR, Shafiei, N, Safarinejad, S. Association of polymorphisms in the estrogen receptors alpha, and beta (ESR1, ESR2) with the occurrence of male infertility and semen parameters. J Steroid Biochem Mol Biol 2010;122:193203.Google Scholar
Su, MT, Chen, CH, Kuo, PH, et al. Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect. Fertil Steril 2010;93:141–9.Google Scholar
Ge, Y-Z, Xu, L-W, Jia, R-P, et al. Association of polymorphisms in estrogen receptors (ESR1 and ESR2) with male infertility: a meta-analysis and systematic review. J Assist Reprod Genet 2014;31:601–11.Google Scholar
Cui, YR, Guo, YH, Qiao, SD, et al. Correlation between SHBG gene polymorphism and male infertility in Han population of Henan province of China: a STROBE-compliant article. Medicine (Baltimore) 2017;96:e7753.Google Scholar
Bachelot, A, Grouthier, V, Courtillot, C, Dulon, J, Touraine, P. Management of endocrine disease: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment. Eur J Endocrinol 2017;176:R167–81.Google Scholar
Falhammar, H, Nyström, HF, Ekström, U, Granberg, S, Wedell, A, Thorén, M. Fertility, sexuality and testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia. Eur J Endocrinol 2012;166:441–9.Google Scholar
Bry-Gauillard, H, Cartes, A, Young, J. Mitotane for 21-hydroxylase deficiency in an infertile man. N Engl J Med 2014;371:2042–4.Google Scholar
Mendonca, BB, Bloise, W, Arnhold, IJ, et al. Male pseudohermaphroditism due to nonsalt-losing 3 beta-hydroxysteroid dehydrogenase deficiency: gender role change and absence of gynecomastia at puberty. J Steroid Biochem 1987;28:669–75.Google Scholar
Kang, H-J, Imperato-McGinley, J, Zhu, Y-S, Rosenwaks, Z. The effect of 5α-reductase-2 deficiency on human fertility. Fertil Steril 2014;101:310–16.Google Scholar
Rochira, V, Carani, C. Aromatase deficiency in men: a clinical perspective. Nat Rev Endocrinol 2009;5:559–68.Google Scholar
Morishima, A, Grumbach, MM, Simpson, ER, Fisher, C, Qin, K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995;80:3689–98.Google Scholar
Hortas, ML, Castilla, JA, Gil, MT, et al. Decreased sperm function of patients with myotonic muscular dystrophy. Hum Reprod 2000;15:445–-8.CrossRefGoogle ScholarPubMed
Takeda, R, Ueda, M. Pituitary-gonadal function in male patients with myotonic dystrophy- serum luteinizing hormone, follicle stimulating hormone and testosterone levels and histological dmaage of the testis. Acta Endocrinol (Copenh) 1977;84:382–9.Google Scholar
De Felice, F, Marchetti, C, Marampon, F, Cascialli, G, Muzii, L, Tombolini, V. Radiation effects on male fertility. Andrology 2019;7:27.Google Scholar
Chan, PTK. Fertility after cancer in men. Can Urol Assoc J 2009;3:223–4.Google Scholar
O’Flaherty, C, Hales, BF, Chan, P, Robaire, B. Impact of chemotherapeutics and advanced testicular cancer or Hodgkin lymphoma on sperm deoxyribonucleic acid integrity. Fertil Steril 2010;94:1374–9.Google Scholar
Allen, CM, Lopes, F, Mitchell, R, Spears, N. How does chemotherapy treatment damage the prepubertal testis? Reproduction 2018;156:R209–33.Google Scholar
Nachtigall, LB, Boepple, PA, Pralong, FP, Crowley, WF Jr. Adult-onset idiopathic hypogonadotropic hypogonadism – a treatable form of male infertility. N Engl J Med 1997;336:410–15.Google Scholar
Hayes, FJ, Seminara, SB, Crowley, WF Jr. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am 1998;27:739–63, vii.Google Scholar
Cho, H-J, Shan, Y, Whittington, NC, Wray, S. Nasal placode development, GnRH neuronal migration and Kallmann syndrome. Front Cell Dev Biol 2019;7:121.Google Scholar
Lima Amato, LG, Latronico, AC, Gontijo Silveira, LF. Molecular and genetic aspects of congenital isolated hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am 2017;46:283303.Google Scholar
Dode, C, Hardelin, JP. Kallmann syndrome. Eur J Hum Genet 2009;17:139–46.Google Scholar
Stamou, MI, Cox, KH, Crowley, WF Jr. Discovering genes essential to the hypothalamic regulation of human reproduction using a human disease model: adjusting to life in the “-omics” era. Endocr Rev 2015;36:603–21.Google Scholar
Castinetti, F, Reynaud, R, Quentien, MH, et al. Combined pituitary hormone deficiency: current and future status. J Endocrinol Invest 2015;38:112.Google Scholar
Romero, CJ, Pine-Twaddell, E, Radovick, S. Novel mutations associated with combined pituitary hormone deficiency. J Mol Endocrinol 2011;46:R93102.Google Scholar
Cemeroglu, AP, Coulas, T, Kleis, L. Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study. J Pediatr Endocrinol Metab 2015;28:1057–63.Google Scholar
Huhtaniemi, IT, Themmen, AP. Mutations in human gonadotropin and gonadotropin-receptor genes. Endocrine 2005;26:207–18.Google Scholar
Barton, DJ, Kumar, RG, McCullough, EH, et al. Persistent hypogonadotropic hypogonadism in men after severe traumatic brain injury: temporal hormone profiles and outcome prediction. J Head Trauma Rehabil 2016;31:277–87.Google Scholar
Bavisetty, S, Bavisetty, S, McArthur, DL, et al. Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 2008;62:1080–93; discussion 93–4.Google Scholar
Vance, ML. Hypopituitarism. N Engl J Med 1994;330:1651–62.Google Scholar
Gudin, JA, Laitman, A, Nalamachu, S. Opioid related endocrinopathy. Pain Med 2015;16 Suppl 1:S915.Google Scholar
O’Rourke, TK Jr, Wosnitzer, MS. Opioid-induced androgen deficiency (OPIAD): diagnosis, management, and literature review. Curr Urol Rep 2016;17:76.Google Scholar
Anderson, RC, Newton, CL, Anderson, RA, Millar, RP. Gonadotropins and their analogs: current and potential clinical applications. Endocr Rev 2018;39:911–37.Google Scholar
Christou, MA, Christou, PA, Markozannes, G, Tsatsoulis, A, Mastorakos, G, Tigas, S. Effects of anabolic androgenic steroids on the reproductive system of ahletes and recreational users: a systematic review and meta-analysis. Sports Med 2017;47:1869–83.Google Scholar
Rahnema, CD, Lipshultz, LI, Crosnoe, LE, Kovac, JR, Kim, ED. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril 2014;101:1271–9.Google Scholar
Liu, PY, Swerdloff, RS, Christenson, PD, Handelsman, DJ, Wang, C. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet 2006;367:1412–20.Google Scholar
Liu, PY, Baker, HW, Jayadev, V, Zacharin, M, Conway, AJ, Handelsman, DJ. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab 2009;94:801–8.Google Scholar
Burger, HG, de Kretser, DM, Hudson, B, Wilson, JD. Effects of preceding androgen therapy on testicular response to human pituitary gonadotropin in hypogonadotropic hypogonadism: a study of three patients. Ferti Steril 1981;35:64–8.Google Scholar
Pitteloud, N, Hayes, FJ, Dwyer, A, Boepple, PA, Lee, H, Crowley, WF Jr. Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 2002;87:4128–36.Google Scholar
Liu, PY, Gebski, VJ, Turner, L, Conway, AJ, Wishart, SM, Handelsman, DJ. Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men. Hum Reprod 2002;17:625–33.Google Scholar
Finkel, DM, Phillips, JL, Snyder, PJ. Stimulation of spermatogenesis by gonadotropins in men with hypogonadotropic hypogonadism. N Engl J Med 1985;313:651–5.Google Scholar
Dwyer, AA, Raivio, T, Pitteloud, N. Gonadotrophin replacement for induction of fertility in hypogonadal men. Best Pract Res Clin Endocrinol Metab 2015;29:91103.CrossRefGoogle ScholarPubMed
Dwyer, AA, Raivio, T, Pitteloud, N. Management of endocrine disease: Reversible hypogonadotropic hypogonadism. Eur J Endocrinol 2016;174:R267–74.Google Scholar
Young, J, Couzinet, B, Chanson, P, Brailly, S, Loumaye, E, Schaison, G. Effects of human recombinant luteinizing hormone and follicle-stimulating hormone in patients with acquired hypogonadotropic hypogonadism: study of Sertoli and Leydig cell secretions and interactions. J Clin Endocrinol Metab 2000;85:3239–44.Google Scholar
Sherins, RJ. Evaluation and management of men with hypogonadotropic hypogonadism. In: Garcia, CR, Mastroianni, I, Amelar, RD, Dubin, L, eds. Current Therapy in Infertility. Philadelphia, PA: BC Decker, 1984; pp. 147–51.Google Scholar
Kobori, Y, Suzuki, K, Iwahata, T, et al. Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism. Syst Biol Reprod Med 2015;61:110–12.Google Scholar
Sinisi, AA, Esposito, D, Bellastella, G, et al. Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism. J Endocrinol Invest 2010;33:618–23.Google Scholar
Zacharin, M, Sabin, MA, Nair, VV, Dabadghao, P. Addition of recombinant follicle-stimulating hormone to human chorionic gonadotropin treatment in adolescents and young adults with hypogonadotropic hypogonadism promotes normal testicular growth and may promote early spermatogenesis. Fertil Steril 2012;98:836–42.Google Scholar
Santoro, N, Filicori, M, Crowley, WF Jr. Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone. Endocr Rev 1986;7:1123.Google Scholar
Buchter, D, Behre, HM, Kliesch, S, Nieschlag, E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998;139:298303.Google Scholar
Liu, L, Banks, SM, Barnes, KM, Sherins, RJ. Two-year comparison of testicular responses to pulsatile gonadotropin-releasing hormone and exogenous gonadotropins from the inception of therapy in men with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1988;67:1140–5.Google Scholar
Heller, CG, Clermont, Y. Spermatogenesis in man: an estimate of its duration. Science 1963;140:184–6.Google Scholar
Sallmen, M, Sandler, DP, Hoppin, JA, Blair, A, Baird, DD. Reduced fertility among overweight and obese men. Epidemiology 2006;17:520–3.Google Scholar
Nguyen, RH, Wilcox, AJ, Skjaerven, R, Baird, DD. Men’s body mass index and infertility. Hum Reprod 2007;22:2488–93.Google Scholar
Pauli, EM, Legro, RS, Demers, LM, Kunselman, AR, Dodson, WC, Lee, PA. Diminished paternity and gonadal function with increasing obesity in men. Fertil Steril 2008;90:346–51.Google Scholar
Martini, AC, Tissera, A, Estofan, D, et al. Overweight and seminal quality: a study of 794 patients. Fertil Steril 2010;94:1739–43.Google Scholar
Kort, HI, Massey, JB, Elsner, CW, et al. Impact of body mass index values on sperm quantity and quality. J Androl 2006;27:450–2.Google Scholar
Hakonsen, LB, Thulstrup, AM, Aggerholm, AS, et al. Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men. Reprod Health 2011;8:24.Google Scholar
Hammoud, AO, Meikle, AW, Reis, LO, Gibson, M, Peterson, CM, Carrell, DT. Obesity and male infertility: a practical approach. Semin Reprod Med 2012;30:486–95.Google Scholar
Lazaros, L, Hatzi, E, Markoula, S, et al. Dramatic reduction in sperm parameters following bariatric surgery: report of two cases. Andrologia 2012;44:428–32.Google Scholar
Reis, LO, Dias, FG. Male fertility, obesity, and bariatric surgery. Reprod Sci 2012;19:778–85.Google Scholar
Shah, DK, Ginsburg, ES. Bariatric surgery and fertility. Curr Opin Obstet Gynecol 2010;22:248–54.Google Scholar
Roth, MY, Amory, JK, Page, ST. Treatment of male infertility secondary to morbid obesity. Nat Clin Pract Endocrinol Metab 2008;4:415–19.CrossRefGoogle ScholarPubMed
Pavlovich, CP, King, P, Goldstein, M, Schlegel, PN. Evidence of a treatable endocrinopathy in infertile men. J Urol 2001;165:837–41.Google Scholar
Gabrielsen, JS, Lamb, DJ, Lipshultz, LI. Iron and a man’s reproductive health: the good, the bad, and the ugly. Curr Urol Rep 2018;19:60.Google Scholar
De Sanctis, V, Soliman, AT, Elsedfy, H, et al. Gonadal dysfunction in adult male patients with thalassemia major: an update for clinicians caring for thalassemia. Expert Rev Hematol 2017;10:1095–106.Google Scholar
Velazquez, EM, Bellabarba, AG. Effects of thyroid status on pituitary gonadotropin and testicular reserve in men. Arch Androl 1997;38:8592.Google Scholar
Krajewska-Kulak, E, Sengupta, P. Thyroid function in male infertility. Front Endocrinol 2013;4:174.Google Scholar
Krassas, GE, Poppe, K, Glinoer, D. Thyroid function and human reproductive health. Endocr Rev 2010;31:702–55.Google Scholar
La Vignera, S, Vita, R, Condorelli, RA, et al. Impact of thyroid disease on testicular function. Endocrine 2017;58:397407.Google Scholar
Rusz, A, Pilatz, A, Wagenlehner, F, et al. Influence of urogenital infections and inflammation on semen quality and male fertility. World J Urol 2012;30:2330.Google Scholar
Gimenes, F, Souza, RP, Bento, JC, et al. Male infertility: a public health issue caused by sexually transmitted pathogens. Nat Rev Urol 2014;11:672–87.Google Scholar
Weidner, W, Pilatz, A, Diemer, T, Schuppe, HC, Rusz, A, Wagenlehner, F. Male urogenital infections: impact of infection and inflammation on ejaculate parameters. World J Urol 2013;31:717–23.Google Scholar
Garolla, A, Pizzol, D, Bertoldo, A, Menegazzo, M, Barzon, L, Foresta, C. Sperm viral infection and male infertility: focus on HBV, HCV, HIV, HPV, HSV, HCMV, and AAV. J Reprod Immunol 2013;100:20–9.Google Scholar
Barnes, A, Riche, D, Mena, L, et al. Efficacy and safety of intrauterine insemination and assisted reproductive technology in populations serodiscordant for human immunodeficiency virus: a systematic review and meta-analysis. Fertil Steril 2014;102:424–34.Google Scholar
Palermo, GD, Neri, QV, Rosenwaks, Z. To ICSI or Not to ICSI. Semin Reprod Med 2015;33:92102.Google Scholar

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