Abstract
Affected patients with hypogonadism have unnaturally low amounts of sex hormones that produce male and female sex characteristics. Males who suffer from this condition lack testosterone, while females fail to produce enough estrogen. Hypogonadism may be present at birth, or it may take effect years later following injury or illness to the sex glands. Hypogonadism has remarkable associations with variable medical disorders; however, it is characterized by a distinctive association with variable neurological disorders: such as epilepsy, ataxia, dysmyelination, nerve muscle disease, movement disorders, mental retardation and deafness. The remarkable neurological diseases with hypogonadism should not basically be regarded as coincidental findings, but possibly related to an intrinsic pathophysiological association.
Similar content being viewed by others
References
Abid F et al (1978) Moebius syndrome, peripheral neuropathy and hypogonadotropic hypogonadism. J Neurol Sci 35(2–3):309–315
Al-Harbi TM et al (2008) Hypogonadism is common in men with myopathies. J Clin Neuromuscul Dis 9(4):397–401
Aluclu MU, Bahceci S, Bahceci M (2007) A rare embryological malformation of brain—Dandy-Walker syndrome—and its association with Kallmann’s syndrome. Neuro Endocrinol Lett 28(3):255–258
Baraitser M, Rudge P (1996) Moebius syndrome, an axonal neuropathy and hypogonadism. Clin Dysmorphol 5(4):351–355
Boltshauser E, Meyer M, Deonna T (1978) Klinefelter syndrome and neurological disease. J Neurol 219(4):253–259
Boucher BJ, Gibberd FB (1969) Familial ataxia, hypogonadism and retinal degeneration. Acta Neurol Scand 45(4):507–510
Braga-Neto P et al (2010) Hypergonadotropic hypogonadism and cerebellar ataxia: an unusual association. Arq Neuropsiquiatr 68(1):132–134
Braun SA et al (2011) POEMS syndrome. An interdisciplinary clinical challenge. Hautarzt 62(10):722–725
Cariboni A et al (2004) The product of X-linked Kallmann’s syndrome gene (KAL1) affects the migratory activity of gonadotropin-releasing hormone (GnRH)-producing neurons. Hum Mol Genet 13(22):2781–2791
Chudley AE et al (1985) Multicore disease in sibs with severe mental retardation, short stature, facial anomalies, hypoplasia of the pituitary fossa, and hypogonadotropic hypogonadism. Am J Med Genet 20(1):145–158
Conte G et al (1976) Benign muscular dystrophy with hypergonadotropic hypogonadism and congenital cataract. Minerva Med 67(33):2104–2112
Coutinho E et al (2010) Tremor and white matter lesions in Klinefelter syndrome. Mov Disord 25(12):1993–1994
Delozier-Blanchet CD, Haenggeli CA, Engel E (1989) Microencephalic nanism, severe retardation, hypertonia, obesity, and hypogonadism in two brothers: a new syndrome? J Genet Hum 37(4–5):353–365
Harkulich JF, Marchner TJ, Brown EB (1979) Neurological, neuropsychological, and behavioral correlates of Klinefelter’s syndrome. J Nerv Ment Dis 167(6):359–363
Hojslet PE (1981) Chronic otitis media and hearing loss in Turner’s syndrome. Ugeskr Laeger 143(41):2659–2660
Larbrisseau A, Carpenter S (1982) Rud syndrome: congenital ichthyosis, hypogonadism, mental retardation, retinitis pigmentosa and hypertrophic polyneuropathy. Neuropediatrics 13(2):95–98
Lonnqvist T et al (2009) Recessive twinkle mutations cause severe epileptic encephalopathy. Brain 132(Pt 6):1553–1562
Luoma P et al (2004) Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364(9437):875–882
Madan R et al (2004) MRI findings in Kallmann syndrome. Neurol India 52(4):501–503
Mata S et al (2005) Acute motor axonal neuropathy in a Turner’s syndrome patient with a “potential” celiac disease. J Peripher Nerv Syst 10(2):210–212
McCarthy MM (2010) How it’s made: organisational effects of hormones on the developing brain. J Neuroendocrinol 22(7):736–742
Melberg A et al (1996) Muscle-nerve involvement in autosomal dominant progressive external ophthalmoplegia with hypogonadism. Muscle Nerve 19(6):751–757
Miazgowski T, Eisner M, Czekalski S (1991) Kallman’s syndrome combined with aortic valve anomaly and epilepsy. Pol Tyg Lek 46(19–21):380–382
Mroz T, Mroz K, Tutka P (2010) Androgens and epilepsy. Przegl Lek 67(11):1186–1193
Neuhauser G, Opitz JM (1975) Autosomal recessive syndrome of cerebellar ataxia and hypogonadotropic hypogonadism. Clin Genet 7(5):426–434
Nielsen J (1965) Klinefelter’s syndrome in a neurological ward. Acta Neurol Scand 41:197–214
Nishikawa M et al (1997) Mobius-like syndrome associated with a 1:2 chromosome translocation. Clin Genet 51(2):122–123
Parodi S, Pennuto M (2011) Neurotoxic effects of androgens in spinal and bulbar muscular atrophy. Front Neuroendocrinol 32(4):416–425
Parvari R et al (2001) A recessive contiguous gene deletion of chromosome 2p16 associated with cystinuria and a mitochondrial disease. Am J Hum Genet 69(4):869–875
Pierce SB et al (2010) Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. Am J Hum Genet 87(2):282–288
Poungvarin N, Viriyavejakul A (1991) Myotonia congenita, Klinefelter syndrome and primary hypoparathyroidism: the first report of the unusual combination of three rare diseases in the literature. J Med Assoc Thai 74(3):172–175
Sato I et al (2011) A case with central and peripheral hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) plus cataract. J Neurol Sci 300(1–2):179–181
Savic I (2012) Advances in research on the neurological and neuropsychiatric phenotype of Klinefelter syndrome. Curr Opin Neurol 25(2):138–143
Schiffmann R et al (1997) Leukodystrophy in patients with ovarian dysgenesis. Ann Neurol 41(5):654–661
Steinmuller R, Steinberger D, Muller U (1998) MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, obesity), a novel syndrome: assignment of disease locus to xp21.1–p22.13. Eur J Hum Genet 6(3):201–206
Trevisol-Bittencourt PC, Sander JW (1990) Epilepsy and Turner’s syndrome: report of a case and review of the literature. Arq Neuropsiquiatr 48(3):360–365
Tuck RR et al (1983) Familial spastic paraplegia with Kallmann’s syndrome. J Neurol Neurosurg Psychiatry 46(7):671–674
Uzumcu A et al (2009) Molecular genetic screening of MBS1 locus on chromosome 13 for microdeletions and exclusion of FGF9, GSH1 and CDX2 as causative genes in patients with Moebius syndrome. Eur J Med Genet 52(5):315–320
Vendrame M et al (2010) Epilepsy in Prader-Willi syndrome: clinical characteristics and correlation to genotype. Epilepsy Behav 19(3):306–310
Viswanathan V, Eugster EA (2011) Etiology and treatment of hypogonadism in adolescents. Pediatr Clin North Am 58(5):1181–1200
Winterthun S et al (2005) Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology 64(7):1204–1208
Yang CY et al (2005) Klinefelter’s syndrome with seizure, pseudohypoparathyroidism type Ib and multiple endocrine dysfunctions. J Chin Med Assoc 68(12):585–590
Horvers M et al. (2012) Marinesco-Sjogren syndrome due to SIL1 mutations with a comment on the clinical phenotype. Eur J Paediatr Neurol (epub ahead of print)
Abs R et al (1990) Congenital cerebellar hypoplasia and hypogonadotropic hypogonadism. J Neurol Sci 98(2–3):259–265
Agha A, Thompson CJ (2005) High risk of hypogonadism after traumatic brain injury: clinical implications. Pituitary 8(3–4):245–249
Alazami AM et al (2008) Mutations in C2orf37, encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome. Am J Hum Genet 83(6):684–691
Al-Semari A, Bohlega S (2007) Autosomal-recessive syndrome with alopecia, hypogonadism, progressive extra-pyramidal disorder, white matter disease, sensory neural deafness, diabetes mellitus, and low IGF1. Am J Med Genet A 143(2):149–160
Antzoulatos E et al (2011) MPTP Neurotoxicity and Testosterone Induce Dendritic Remodeling of Striatal Medium Spiny Neurons in the C57Bl/6 Mouse. Parkinsons Dis 2011:138471
Beauchet O (2006) Testosterone and cognitive function: current clinical evidence of a relationship. Eur J Endocrinol 155(6):773–781
Bernard G et al (2011) Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet 89(3):415–423
Bora E et al (2007) A new case of Martsolf syndrome. Genet Couns 18(1):71–75
Cabezas DA et al (2000) A new X linked mental retardation (XLMR) syndrome with short stature, small testes, muscle wasting, and tremor localises to Xq24-q25. J Med Genet 37(9):663–668
Conrad B, Kriebel J, Hetzel WD (1978) Hereditary bimanual synkinesis combined with hypogonadotropic hypogonadism and anosmia in four brothers. J Neurol 218(4):263–274
Day JR et al (1998) The effect of age and testosterone on the expression of glial fibrillary acidic protein in the rat cerebellum. Exp Neurol 151(2):343–346
Edwards JA et al (1976) A new familial syndrome characterized by pigmentary retinopathy, hypogonadism, mental retardation, nerve deafness and glucose intolerance. Am J Med 60(1):23–32
Filosto M et al (2003) Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. Arch Neurol 60(9):1279–1284
Floret D et al (1976) Association between hypogonadotropic hypogonadism and familial deafness: a variation of Kallmann’s syndrome? J Genet Hum 24(Suppl):207–214
Fok AC, Wong MC, Cheah JS (1989) Syndrome of cerebellar ataxia and hypogonadotropic hypogonadism: evidence for pituitary gonadotrophin deficiency. J Neurol Neurosurg Psychiatry 52(3):407–409
Georgopoulos NA et al (2004) Spinocerebellar ataxia and hypergonadotropic hypogonadism associated with familial sensorineural hearing loss. Gynecol Endocrinol 19(2):105–110
Hazama R et al (1981) Chronic progressive external ophthalmoplegia, deafness, neurogenic muscular atrophy and hypergonadotropic hypogonadism (author’s transl). Rinsho Shinkeigaku 21(4):304–310
Hofer P, Lanzenberger R, and Kasper S (2012) Testosterone in the brain: Neuroimaging findings and the potential role for neuropsychopharmacology. Eur Neuropsychopharmacol (epub ahead of print)
Hohl A et al (2009) Hypogonadism after traumatic brain injury. Arq Bras Endocrinol Metabol 53(8):908–914
Houang M et al (2002) Hypogonadotrophic hypogonadism associated with prelingual deafness due to a connexin 26 gene mutation. J Pediatr Endocrinol Metab 15(2):219–223
Ishikawa T et al (2010) A case of autosomal recessive hypomyelinating leukodystrophy without GJA12 mutation presenting a novel phenotype. Rinsho Shinkeigaku 50(1):7–11
Jenkinson EM et al (2011) Newly recognized recessive syndrome characterized by dysmorphic features, hypogonadotropic hypogonadism, severe microcephaly, and sensorineural hearing loss maps to 3p21.3. Am J Med Genet A 155A(12):2910–2915
Kwon DY, Park MH (2009) Hypergonadotropic hypogonadism in spinocerebellar ataxia type 2: a case report. J Sex Med 6(6):1779–1782
Leshinsky-Silver E et al (2002) MEHMO (Mental retardation, Epileptic seizures, Hypogenitalism, Microcephaly, Obesity): a new X-linked mitochondrial disorder. Eur J Hum Genet 10(4):226–230
Lowenthal A et al (1979) Familial cerebellar ataxia with hypogonadism. J Neurol 222(2):75–80
Martsolf JT, Hunter AG, Haworth JC (1978) Severe mental retardation, cataracts, short stature, and primary hypogonadism in two brothers. Am J Med Genet 1(3):291–299
McLennan Y et al (2011) Fragile x syndrome. Curr Genomics 12(3):216–224
Myhre SA, Ruvalcaba RH, Kelley VC (1982) Congenital deafness and hypogonadism: a new X-linked recessive disorder. Clin Genet 22(6):299–307
Nakamura M (2001) Alopecia-anosmia-deafness-hypogonadism syndrome (Johnson type). Ryoikibetsu Shokogun Shirizu 33:165
Nichols NR et al (1993) GFAP mRNA increases with age in rat and human brain. Neurobiol Aging 14(5):421–429
Norton WT et al (1992) Quantitative aspects of reactive gliosis: a review. Neurochem Res 17(9):877–885
Okun MS, McDonald WM, DeLong MR (2002) Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity. Arch Neurol 59(5):807–811
Okun MS et al (2002) Beneficial effects of testosterone replacement for the nonmotor symptoms of Parkinson disease. Arch Neurol 59(11):1750–1753
Sarkey S et al (2008) Classical androgen receptors in non-classical sites in the brain. Horm Behav 53(5):753–764
Schwankhaus JD et al (1989) Neurologic findings in men with isolated hypogonadotropic hypogonadism. Neurology 39(2 Pt 1):223–226
Skre H, Berg K (1977) Linkage studies on Marinesco-Sjogren syndrome and hypergonadotropic hypogonadism. Clin Genet 11(1):57–66
Tetreault M et al (2011) Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy. Am J Hum Genet 89(5):652–655
Vazquez-Lopez M et al (2008) Central hypomyelination, hypogonadotropic hypogonadism and hypodontia: a new leukodystrophy. Rev Neurol 47(4):204–208
Wei J et al (1993) Smith-Fineman-Myers syndrome: report on a large family. Am J Med Genet 47(3):307–311
Whitehouse AJ et al (2010) Fetal androgen exposure and pragmatic language ability of girls in middle childhood: implications for the extreme male-brain theory of autism. Psychoneuroendocrinology 35(8):1259–1264
Wolf NI et al (2005) Leukoencephalopathy with ataxia, hypodontia, and hypomyelination. Neurology 64(8):1461–1464
Aydogan U et al (2012) Increased frequency of anxiety, depression, quality of life and sexual life in young hypogonadotropic hypogonadal males and impacts of testosterone replacement therapy on these conditions. Endocr J (epub ahead of print)
Li ZK et al (2006) Protection of androgen against hypoxic-ischemic brain damage in neonatal rats and possible mechanisms. Zhongguo Dang Dai Er Ke Za Zhi 8(6):441–446
Verhovshek T, L.M. Rudolph, D.R. Sengelaub (2012) Brain-derived neurotrophic factor and androgen interactions in spinal neuromuscular systems. Neuroscience (epub ahead of print)
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Alsemari, A. Hypogonadism and neurological diseases. Neurol Sci 34, 629–638 (2013). https://doi.org/10.1007/s10072-012-1278-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-012-1278-4