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  • Print publication year: 2009
  • Online publication date: May 2010

Chapter 12 - Endocrine evaluation

Summary

In mammals, spermatogenesis begins with diploid stem cells that resemble other somatic cells; it ends with highly specialized motile haploid cells that are remarkably unique in appearance and function. Continuous production of spermatozoa throughout life requires that spermatogonia replenish themselves. Type B spermatogonia undergo mitosis to give rise to diploid primary spermatocytes. The spermatocytes then cross the blood-testis barrier formed by the Sertoli tight junctions to the adluminal compartment. Spermiogenesis refers to the acquisition by the germ cell of several organelles and accessory structures such as the acrosome and the flagellum. Testosterone and follicle-stimulating hormone (FSH) are the two major regulatory hormones of spermatogenesis. FSH binding to its receptor activates adenylate cyclase, and the resultant rise in cAMP triggers binding of cAMP response element modulator (CREM) to ACT (activator of CREM). The complex then acts as a molecular master-switch for a number of genes involved in spermatogenesis.

References

[1] BukerHWG, BurgerHG, de KretserDM, HudsonB. Relative incidence of etiologic disorders in male infertility. In: SantenRJ, SwerdloffRS, eds. Male Reproductive Dysfunctions. New York, NY: Marcel Dekker, 1996: 341–72.
[2] de KretserDM. Male infertility. Lancet 1997; 349: 787–90.
[3] JequierAM, HolmesSC. Primary testicular disease presenting as azoospermia or oligozoospermia in an infertility clinic. Br J Urol 1993; 71: 731–5.
[4] BarracloughCA, WisePM. The role of catecholamines in the regulation of pituitary luteinizing hormone and follicle-stimulating hormone secretion. Endocr Rev 1982; 3: 91–119.
[5] KalraSP, KalraPS. Neural regulation of luteinizing hormone secretion in the rat. Endocr Rev 1983; 4: 311–51.
[6] PlantTM. Gonadal regulation of hypothalamic gonadotropin-releasing hormone release in primates. Endocr Rev 1986; 7: 75–88.
[7] VeldhuisJD, KingJC, UrbanRJ, et al. Operating characteristics of the male hypothalamo-pituitary-gonadal axis: Pulsatile release of testosterone and follicle-stimulating hormone and their temporal coupling with luteinizing hormone. J Clin Endocrinol Metab 1987; 65: 929–41.
[8] JarowJP, ZirkinBR. The androgen microenvironment of the human testis and hormonal control of spermatogenesis. Ann N Y Acad Sci 2005; 1061: 208–20.
[9] ItoT, HortonR. The source of plasma dihydrotestosterone in man. J Clin Invest 1971; 50: 1621–7 .
[10] WilsonJD, GriffinJE, RussellDW. Steroid 5α-reductase 2 deficiency. Endocr Rev 1993; 14: 577–93.
[11] LongcopeC, SatoK, McKayC, HortonR. Aromatization by splanchnic tissue in men. J Clin Endocrinol Metab 1984; 58: 1089–93.
[12] SantenRJ. Is aromatization of testosterone to estradiol required for inhibition of luteinizing hormone secretion in men? J Clin Invest 1975; 56: 1555–63.
[13] WintersSJ, TroenP. Evidence for a role of endogenous estrogen in the hypothalamic control of gonadotropin secretion in men. J Clin Endocrinol Metab 1985; 61: 842–5.
[14] McCullaghDR. Dual endocrine activity of the testes. Science 1932; 76: 19–20.
[15] YingSY. Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle–stimulating hormone. Endocr Rev 1988; 9: 267–93.
[16] de JongFH, RobertsonDM. Inhibin: 1985 update on action and purification. Mol Cell Endocrinol 1985; 42: 95–103.
[17] KolbBA, StanczykFZ, SokolRZ. Serum inhibin B levels in males with gonadal dysfunction. Fertil Steril 2000; 74: 234–8.
[18] TongS, WallaceEM, BurgerHG. Inhibins and activins: clinical advances in reproductive medicine. Clin Endocrinol (Oxf) 2003; 58: 115–27.
[19] GillamMP, MolitchME, LombardiG, ColaoA. Advances in the treatment of prolactinomas. Endocr Rev 2006; 27: 485–534.
[20] SokolRZ, SwerdloffRS. Endocrine evaluation. In: LipshultzLI, HowardsSS, eds. Infertility in the Male, 3rd edn. St. Louis, MO: Mosby Year Book, 1997: 210–18.
[21] BraunsteinGD. Gynecomastia. N Engl J Med 1993; 328: 490–5.
[22] IsmailAA, BarthJH. Endocrinology of gynaecomastia. Ann Clin Biochem 2001; 38: 596–607.
[23] MathurR, BraunsteinGD. Gynecomastia: pathomechanisms and treatment strategies. Horm Res 1997; 48: 95–102.
[24] BainJ, LangevinR, D’CostaM, SandersRM, HuckerS. Serum pituitary and steroid hormone levels in the adult male: one value is as good as the mean of three. Fertil Steril 1988; 49: 123–6.
[25] SantenRJ, BardinCW. Episodic luteinizing hormone secretion in man: pulse analysis, clinical interpretation, physiologic mechanisms. J Clin Invest 1973; 52: 2617–28.
[26] PardridgeWM. Transport of protein-bound hormones into tissues in vivo. Endocr Rev 1981; 2: 103–23.
[27] DunnJF, NisulaBC, RodbardD. Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab 1981; 53: 58–68.
[28] GlassAR, SwerdloffRS, BrayGA, DahmsWT, AtkinsonRL. Low serum testosterone and sex-hormone-binding-globulin in massively obese men. J Clin Endocrinol Metab 1977; 45: 1211–19.
[29] PugeatMM, DunnJF, NisulaBC. Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab 1981; 53: 69–75.
[30] VermeulenA, VerdonckL, KaufmanJM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666–72.
[31] CarruthersM. Androgen Deficiency in the Adult Male: Causes, Diagnosis and Treatment. London: Taylor & Francis, 2004.
[32] HarmanSM, MetterEJ, TobinJD, PearsonJ, BlackmanMR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001; 86: 724–31.
[33] Fernández-ArjonaM, DíazJ, CortesI, et al. Relationship between gonadotrophin secretion, inhibin B and spermatogenesis in oligozoospermic men treated with highly purified urinary follicle-stimulating hormone (uFSH-HP): a preliminary report. Eur J Obstet Gynecol Reprod Biol 2003; 107: 47–51.
[34] KallmannFJ, SchoenfeldWA. The genetic aspects of primary eunuchoidism. Am J Ment Def 1944; 158: 203–36.
[35] TrarbachEB, BaptistaMTM, GarmesHM, HackelC. Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann syndrome and normosmic hypogonadotropic hypogonadism patients. J Endocrinol 2005; 187: 361–8.
[36] OliveiraLMB, SeminaraSB, BeranovaM, et al. The importance of autosomal genes in Kallmann syndrome: genotype–phenotype correlations and neuroendocrine characteristics. J Clin Endocrinol Metab 2001; 86: 1532–8.
[37] BhagavathB, PodolskyRH, OzataM, et al. Clinical and molecular characterization of a large sample of patients with hypogonadotropic hypogonadism. Fertil Steril 2006; 85: 706–13.
[38] SantenRJ, PaulsenCA. Hypogonadotropic eunuchoidism. I. Clinical study of the mode of inheritance. J Clin Endocrinol Metab 1973; 36: 47–54.
[39] NachtigallLB, BoepplePA, PralongFP, CrowleyWF. Adult-onset idiopathic hypogonadotropic hypogonadism: a treatable form of male infertility. N Engl J Med 1997; 336: 410–15.
[40] GiltayJC, DeegeM, BlankensteinRA, et al. Apparent primary follicle-stimulating hormone deficiency is a rare cause of treatable male infertility. Fertil Steril 2004; 81: 693–6.
[41] CarterJN, TysonJE, TolisG, et al. Prolactin-screening tumors and hypogonadism in 22 men. N Engl J Med 1978; 299: 847–52.
[42] FranksS, JacobsHS, MartinN, NabarroJD. Hyperprolactinaemia and impotence. Clin Endocrinol (Oxf) 1978; 8: 277–87.
[43] Ben-JonathanN. Dopamine. a prolactin-inhibiting hormone. Endocr Rev 1985; 6: 564–89.
[44] BayrakA, SaadatP, MorE, et al. Pituitary imaging is indicated for the evaluation of hyperprolactinemia. Fertil Steril 2005; 84: 181–5.
[45] HammoudAO, GibsonM, PetersonCM, HamiltonBD, CarrellDT. Obesity and male reproductive potential. J Androl 2006; 27: 619–26.
[46] PlymateSR. Male hypogonadism. In: BeckerKI, ed. Principles and Practice of Endocrinology and Metabolism. Philadelphia, PA: Lippincott, 1995: 1056–82.
[47] DhindsaS, PrabhakarS, SethiM, et al. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 5462–8.
[48] BonaccorsiAC, AdlerI, FigueiredoJG. Male infertility due to congenital adrenal hyperplasia: testicular biopsy findings, hormonal evaluation, and therapeutic results in three patients. Fertil Steril 1987; 47: 664–70.
[49] StikkelbroeckNM, OttenBJ, PasicA, et al. High prevalence of testicular adrenal rest tumors, impaired spermatogenesis, and Leydig cell failure in adolescent and adult males with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2001; 86: 5721–8.
[50] SokolRZ. Male factor infertility. In: LoboRA, MishellDR, PaulsonRJ, ShoupeD, eds. Infertility, Contraception, and Reproductive Endocrinology, 4th edn. Malden MA: Blackwell, 1997: 547–66.
[51] SokolRZ, McClureRD, PetersonM, SwerdloffRS. Gonadotropin therapy failure secondary to human chorionic gonadotropin-induced antibodies. J Clin Endocrinol Metab 1981; 52: 929–32.
[52] WhittenSJ, NangiaAK, KolettisPN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril 2006; 86: 1664–8.
[53] FukagaiT, KurosawaK, SudoN, et al. Bilateral testicular tumors in an infertile man previously treated with follicle-stimulating hormones. Urology 2005; 65: 592.e16–18.
[54] HoffmanAR, CrowleyWF. Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone. N Engl J Med 1982; 307: 1237–41.
[55] KlieschS, BehreHM, NieschlagE. High efficacy of gonadotropin or pulsatile gonadotropin-releasing hormone treatment in hypogonadotropic hypogonadal men. Eur J Endocrinol 1994; 131: 347–54.
[56] KlingmullerD, SchweikertHU. Maintenance of spermatogenesis by intranasal administration of gonadotropin-releasing hormone in patients with hypothalamic hypogonadism. J Clin Endocrinol Metab 1985; 61: 868–72.
[57] SkarinG, NilliusSJ, WibellL, WideL. Chronic pulsatile low dose GnRH therapy for induction of testosterone production and spermatogenesis in a man with secondary hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1982; 55: 723–6.
[58] AttiaAM, Al-InanyHG, ProctorML. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev 2006; (1): CD005071.
[59] BoulouxP, WarneDW, LoumayeE, FSH Study Group in Men’s Infertility. Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism. Fertil Steril 2002; 77: 270–3.
[60] LiuPY, HandelsmanDJ. The present and future state of hormonal treatment for male infertility. Hum Reprod Update 2003; 9: 9–23.
[61] LiuPY, TurnerL, RushfordD, et al. Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men. Hum Reprod 1999; 14: 1540–5.
[62] ShohamZ, ConwayCS, OstergaardH, et al. Cotreatment with growth hormone for induction of spermatogenesis in patients with hypogonadotropic hypogonadism. Fertil Steril 1992; 57: 1044–51.
[63] HammarM, BergAA. Long term androgen replacement therapy does not preclude gonadotrophin-induced improvement on spermatogenesis. Scand J Urol Nephrol 1990; 24: 17–19.
[64] LeySB, LeonardJM. Male hypogonadotropic hypogonadism: factors influencing response to human chorionic gonadotropin and human menopausal gonadotropin, including prior endogenous androgens. J Clin Endocrinol Metab 1985; 61: 746–52.
[65] BojesenA, JuulS, GravholtCH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 2003; 88: 622–6.
[66] BojesenA, JuulS, BirkebaekNH, GravholtCH. Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J Clin Endocrinol Metab 2006; 91: 1254–60.
[67] SimmPJ, ZacharinMR. The psychosocial impact of Klinefelter syndrome: a year review. J Pediatr Endocrinol Metab 2006; 19: 499–505.
[68] WeissJR, MoysichKB, SwedeH. Epidemiology of male breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 20–6.
[69] VernaeveV, StaessenC, VerheyenG, et al. Can biological or clinical parameters predict testicular sperm recovery in 47, XXY Klinefelter’s syndrome patients? Hum Reprod 2004; 19: 1135–9.
[70] SokolRZ. Environmental toxins and male fertility. In: KandeelF, ed. Male Reproductive Dysfunction: Pathophysiology and Treatment. New York, NY: Informa Healthcare, 2007: 203–7.
[71] SchiffJD, PalermoGD, VeeckLL, et al. Success of testicular sperm injection and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab 2005; 90: 6263–7.
[72] ZitzmannM, NordhoffV, von SchönfeldV, et al. Elevated follicle-stimulating hormone levels and the chances for azoospermic men to become fathers after retrieval of elongated spermatids from cryopreserved testicular tissue. Fertil Steril 2006; 86: 339–47.
[73] ForestaC, BettellaA, GarollaA, AmbrosiniG, FerlinA. Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone: a prospective, controlled, randomized clinical study. Fertil Steril 2005; 84: 654–61.
[74] HauserR, Temple-SmithPD, SouthwickGJ, de KretserD. Fertility in cases of hypergonadotropic azoospermia. Fertil Steril 1995; 63: 631–6.
[75] PavlovichCP, KingP, GoldsteinM, SchlegelPN. Evidence of a treatable endocrinopathy in infertile men. J Urol 2001; 165: 837–41.
[76] RamanJD, SchlegelPN. Aromatase inhibitors for male infertility. J Urol 2002; 167: 624–9.
[77] JohnsonL, GeorgeFW, NeavesWB, et al. Characterization of the testicular abnormality in 5α-reductase deficiency. J Clin Endocrinol Metab 1986; 63: 1091–9.
[78] DowsingAT, YongEL, ClarkM, et al. Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene. Lancet 1999; 354: 640–3.
[79] Davis-DaoCA, TuazonED, SokolRZ, CortessisVK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrinol Metab 2007; 92: 4319–26.
[80] GriffinJE. Androgen resistance: the clinical and molecular spectrum. N Engl J Med 1992; 326: 611–18.
[81] WilsonJD. Roosters, Reifenstein’s syndrome and hormone resistance. N Engl J Med 1977; 297: 386–7.
[82] AimanJ, GriffinJE. The frequency of androgen receptor deficiency in infertile men. J Clin Endocrinol Metab 1982; 54: 725–32.
[83] HijaziRA, CunninghamGR. Andropause: is androgen replacement therapy indicated for the aging male? Ann Rev Med 2005; 56: 117–37.
[84] MorleyJE, KaiserFE, PerryHM, et al. Longitudinal changes in testosterone, luteinzing hormone, and follicle-stimulating hormone in healthy older men. Metabolism 1997; 46: 410–13.
[85] TravisonTG, AraujoAB, KupelianV, O’DonnellAB, McKinlayJB. The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metab 2007; 92: 549–55.
[86] FeldmanHA, LongcopeC, DerbyCA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002; 87: 589–98.
[87] GrayA, FeldmanHA, McKinlayJB, LongcopeC. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991; 73: 1016–25.
[88] HarmanSM, TsitourasPD. Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing hormone, and Leydig cell response to human chorionic gonadotropin. J Clin Endocrinol Metab 1980; 51: 35–40.
[89] KorenmanSG, MorleyJE, MooradianAD, et al. Secondary hypogonadism in older men: its relation to impotence. J Clin Endocrinol Metab 1990; 71: 963–9.
[90] DeslypereJP, KaufmanJM, VermeulenT, et al. Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men. J Clin Endocrinol Metab 1987; 64: 68–73.
[91] LuboshitzkyR, Shen-OrrZ, HererP. Middle-aged men secrete less testosterone at night than young healthy. J Clin Endocrinol Metab 2003; 88: 3160–6.
[92] TenoverJS, MatsumotoAM, CliftonDK, BremnerWJ. Age-related alterations in the circadian rhythms of pulsatile luteinizing hormone and testosterone secretion in healthy men. J Gerontol 1988; 43: M163–9.
[93] HarenMT, WittertGA, ChapmanIM, CoatesP, MorleyJE. Effect of oral testosterone undecanoate on visuospatial cognition, mood and quality of life in elderly men with low-normal gonadal status. Maturitas 2005; 50: 124–33.
[94] HeinemanAJ, ZimmermannJ, VermeulenA, ThielC. A new aging males’ symptoms (AMS) rating scale. Aging Male 1998; 2: 105–14.
[95] MorleyJE, CharltonE, PatrickP, et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 2000; 49: 1239–43.
[96] SmithKW, FeldmanHA, McKinlayJB. Construction and field validation of a self-administered screener for testosterone deficiency (hypogonadism) in ageing men. Clin Endocrinol (Oxf) 2000; 53: 703–11.
[97] MorleyJE, PerryHM, KevorkianRT, PatrickP. Comparison of screening questionnaires for the diagnosis of hypogonadism. Maturitas 2006; 53: 424–9.
[98] BhasinS, CunninghamGR, HayesFJ, et al. Clinical practice guideline: testosterone therapy in adult men with androgen deficiency syndromes: An Endocrine Soceity clinical practice guideline. J Clin Endocrinol Metab 2006; 91: 1995–2010.
[99] AminorroayaA, KelleherS, ConwayAJ, LyLP, HandelsmanDJ. Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men. Eur J Endocrinol 2005; 152: 881–6.
[100] FinasD, Bals-PratschM, SandmannJ, et al. Quality of life in elderly men with androgen deficiency. Andrologia 2006; 38: 48–53.
[101] SnyderPJ, PeacheyH, HannoushP, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999; 84: 1966–72.
[102] SnyderPJ, PeacheyH, HannoushP, et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 1999; 84: 2647–53.
[103] WangC, CunninghamG, DobsA, et al. Long-term testosterone gel (AndroGel®) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004; 89: 2085–98.
[104] BhasinS, BagatellCJ, BremnerWJ, et al. Issues in testosterone replacement in older men. J Clin Endocrinol Metab 1998; 83: 3435–45.
[105] SnyderPJ. Effects of age on testicular function and consequences of testosterone treatment. J Clin Endocrinol Metab 2001; 86: 2369–72.
[106] TenoverJL. Male hormone replacement therapy including “andropause.” Endocrinol Metab Clin North Am 1998; 27: 969–87.
[107] CalofOM, SinghAB, LeeML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol 2005; 60A: 1451–7.
[108] SnyderPJ, LawrenceDA. Treatment of male hypogonadism with testosterone enanthate. J Clin Endocrinol Metab 1980; 51: 1335–9.
[109] SokolRZ, PalaciosA, CampfieldLA, SaulC, SwerdloffRS. Comparison of the kinetics of injectable testosterone in eugonadal and hypogonadal men. Fertil Steril 1982; 37: 425–30.
[110] MeikleAW, ArverS, DobsAS, et al. Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of application site. A clinical research center study. J Clin Endocrinol Metab 1996; 81: 1832–40.
[111] YuZ, GuptaSK, HwangSS, et al. Testosterone pharmacokinetics after application of an investigational transdermal system in hypogonadal men. J Clin Pharmacol 1997; 37: 1139–45.
[112] SwerdloffRS, WangC, CunninghamG, et al. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000; 85: 4500–10.
[113] MoralesA. Monitoring androgen replacement therapy: testosterone and prostate safety. J Endocrinol Invest 2005; 28 (3 Suppl): 122–7.
[114] GenazzaniAR, IngleseS, LombardiI, et al. Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. Aging Male 2004; 7: 133–43.
[115] MoralesAJ, HaubrichRH, HwangJY, AsakuraH, YenSS. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf) 1998; 49: 421–32.
[116] MoralesAJ, NolanJJ, NelsonJC, YenSS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 1994; 78: 1360–7.
[117] NairKS, RizzaRA, O’BrienP, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006; 355: 1647–59.
[118] AcacioBD, StanczykFZ, MullinP, et al. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men. Fertil Steril 2004; 81: 595–604.