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Pharmachosexology: Use of Sex Hormones in Psychiatric Conditions

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Sexual Dysfunctions in Mentally Ill Patients

Abstract

Increasing evidence supports the influence of sex hormones on the central nervous system’s (CNS) plasticity and mental state. Indeed, gender differences have been described in proneness to many psychiatric and neurological diseases, among which differences in incidence between men and women have been reported. In addition, biological aspects can affect the clinical presentation of some mental diseases. In fact, changes in hormonal levels across the life span may also affect mental illness expression.

The present contribution is aimed at summarizing the possible interplay between gonadal hormones and mental health. In particular, sex hormones may be relevant in mentally ill patients for three reasons: (1) they can play a role in the pathophysiology of psychiatric disorders; (2) they may be used to treat mental illness; and (3) treatment with sex hormones may have psychiatric side effects. The available literature exploring the relationship between sex hormones and psychiatric conditions highlights the importance of a multidisciplinary assessment in mentally ill patients. Prospective randomized studies investigating the impact of hormone replacement therapy on psychological profiles may provide crucial information in better understanding sex hormones’ influences on mental state, as well as optimizing treatments in mentally vulnerable patients.

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References

  1. Kulkarni J, Gurvich C, Gilbert H, Mehmedbegovic F, Mu L, Marston N, Gavrilidis E, de Castella A, Aust NZ. Hormone modulation: a novel therapeutic approach for women with severe mental illness. J Psychiatry. 2008;42(1):83–8.

    Google Scholar 

  2. Cohen-Bendahan CC, van de Beeka C, Berenbaum SA. Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings. Neurosci Biobehav Rev. 2005;29:353–84.

    Article  CAS  PubMed  Google Scholar 

  3. Raznahan A, Lee Y, Stidd R, Long R, Greenstein D, Clasen L, Addington A, Gogtay N, Rapoport JL, Giedd JN. Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence. Proc Natl Acad Sci U S A. 2010;107:16988–93.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Golightly L, Young A. Sex hormones and mental health. Adv Psychiatr Treat. 1995;5:126–34.

    Article  Google Scholar 

  5. Gobinath AR, Choleris E, Galea LA. Sex, hormones, and genotype interact to influence psychiatric disease, treatment, and behavioral research. J Neurosci Res. 2017;95:50–64.

    Article  CAS  PubMed  Google Scholar 

  6. Angst J, Gamma A, Gastpar M, Lepine JP, Mendlewicz J, Tylee A, Depression Research in European Society Study. Gender differences in depression. Epidemiological findings from the European DEPRES I and II studies. Eur Arch Psychiatry Clin Neurosci. 2002;252:201–9.

    Article  CAS  PubMed  Google Scholar 

  7. Li SH, Graham BM. Why are women so vulnerable to anxiety, trauma-related and stress related disorders? The potential role of sex hormones. Lancet. 2016;4:73–82.

    Google Scholar 

  8. Ruitenberg A, Ott A, Van Swieten JC, Hofman A, Breteler MM. Incidence of dementia: does gender make a difference? Neurobiol Aging. 2001;22:575–80.

    Article  CAS  PubMed  Google Scholar 

  9. Zhou DF, Wu CS, Qi H, Fan JH, Sun XD, Como P, Qiao YL, Zhang L, Kieburtz K. Prevalence of dementia in rural China: impact of age, gender and education. Acta Neurol Scand. 2006;114:273–80.

    Article  CAS  PubMed  Google Scholar 

  10. Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65:91–598.

    Article  Google Scholar 

  11. Werlin DM, Geschwindm DH. Understanding sex bias in autism spectrum disorder. Proc Natl Acad Sci. 2013;110:4868–9.

    Article  Google Scholar 

  12. Ramtekkar UP, Reiersen AM, Todorov AA, Todd RD. Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11. J Am Acad Child Adolesc Psychiatry. 2010;49:217–228, e211–e213.

    PubMed  PubMed Central  Google Scholar 

  13. Rucklidge JJ. Gender differences in attention–deficit/hyperactivity disorder. Psychiatr Clin North Am. 2010;33:357–73.

    Article  PubMed  Google Scholar 

  14. Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, Nelson LM. Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003;157:1015–22.

    Article  Google Scholar 

  15. Woolley CS, Gould E, Frankfurt M, Mcewen BS. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci. 1990;10:4035–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593–602.

    Article  PubMed  Google Scholar 

  17. Steiner M, Dunn E, Born L. Hormones and mood: from menarche to menopause and beyond. J Affect Disord. 2003;74:67–83.

    Article  CAS  PubMed  Google Scholar 

  18. Keyes KM, Cheslack-Postava K, Westhoff C, Heim CM, Haloossim M, Walsh K, Koenen K. Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States. Am J Epidemiol. 2013;178:1378–88.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bergemann N, Parzer P, Nagl I, Salbach B, Runnebaum B, Mundt C, Resch F. Acute psychiatric admission and menstrual cycle phase in women with schizophrenia. Arch Womens Ment Health. 2002;5:119–26.

    Article  CAS  PubMed  Google Scholar 

  20. McHenry J, Carrier N, Hull E, Kabbaj M. Sex differences in anxiety and depression: role of testosterone. Front Neuroendocrinol. 2014;1:42–57.

    Article  CAS  Google Scholar 

  21. Ciocca G, Limoncin E, Carosa E, Di Sante S, Gravina GL, Mollaioli D, Gianfrilli D, Lenzi A, Jannini EA. Is testosterone a food for the brain? Sex Med Rev. 2016;4:15–25.

    Article  PubMed  Google Scholar 

  22. Zuloaga DG, Puts DA, Jordan CL, Breedlove SM. The role of androgen receptors in the masculinization of brain and behavior: what we’ve learned from the testicular feminization mutation. Horm Behav. 2008;53:613–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Frye CA, Edinger K, Sumida K. Androgen administration to aged male mice increases anti-anxiety behavior and enhances cognitive performance. Neuropsychopharmacology. 2008;33:1049–61.

    Article  CAS  PubMed  Google Scholar 

  24. Frye CA, Edinger KL. Testosterone’s metabolism in the hippocampus may mediate its anti-anxiety effects in male rats. Pharmacol Biochem Behav. 2004;78:473–81.

    Article  CAS  PubMed  Google Scholar 

  25. Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;4:289–305.

    Article  Google Scholar 

  26. Bandini E, Corona G, Ricca V, Fisher AD, Lotti F, Sforza A, Faravelli C, Forti G, Mannucci E, Maggi M. Hysterical traits are not from the uterus but from the testis: a study in men with sexual dysfunction. J Sex Med. 2009;6:2321–31.

    Article  PubMed  Google Scholar 

  27. DiBlasio CJ, Hammett J, Malcolm JB, Judge BA, Womack JH, Kincade MC, Ogles ML, Mancini JG, Patterson AL, Wake RW, Derweesh IH. Prevalence and predictive factors for the development of de novo psychiatric illness in patients receiving androgen deprivation therapy for prostate cancer. Can J Urol. 2008;15:4249–56.

    PubMed  Google Scholar 

  28. Kanayama G, Amiaz R, Seidman S, Pope HG Jr. Testosterone supplementation for depressed men: current research and suggested treatment guidelines. Exp Clin Psychopharmacol. 2007;15(6):529–38.

    Article  CAS  PubMed  Google Scholar 

  29. Anestis SF. Testosterone in juvenile and adolescent male chimpanzees (pan troglodytes): effects of dominance rank, aggression, and behavioral style. Am J Phys Anthropol. 2006;130:536–45.

    Article  PubMed  Google Scholar 

  30. Muehlenbein MP, Watts DP, Whitten PL. Dominance rank and fecal testosterone levels in adult male chimpanzees (Pan troglodytes schweinfurthii) at Ngogo, Kibale National Park, Uganda. Am J Primatol. 2004;64:71–82.

    Article  PubMed  Google Scholar 

  31. Rose RM, Holaday JW, Bernstein IS. Plasma testosterone, dominance rank and aggressive behavior in male rhesus monkeys. Nature. 1971;231:366–8.

    Article  CAS  PubMed  Google Scholar 

  32. Klinkova E, Heistermann M, Hodges JK. Social parameters and urinary testosterone level in male chimpanzees (Pan troglodytes). Horm Behav. 2004;46:474–81.

    Article  CAS  PubMed  Google Scholar 

  33. Fisher AD, Bandini E, Rastrelli G, Corona G, Monami M, Mannucci E, Maggi M. Sexual and cardiovascular correlates of male unfaithfulness. J Sex Med. 2012;6:1508–18.

    Article  Google Scholar 

  34. Fisher AD, Bandini E, Corona G, Monami M, Cameron Smith M, Melani C, Balzi D, Forti G, Mannucci E, Maggi M. Stable extramarital affairs are breaking the heart. Int J Androl. 2012;1:11–7.

    Article  CAS  Google Scholar 

  35. Fisher AD, Rastrelli G, Bandini E, Corona G, Balzi D, Melani C, Monami M, Matta V, Mannucci E, Maggi M. Metabolic and cardiovascular outcomes of fatherhood: results from a cohort of study in subjects with sexual dysfunction. J Sex Med. 2012;9:2785–94.

    Article  PubMed  Google Scholar 

  36. Fisher AD, Corona G, Bandini E, Mannucci E, Lotti F, Boddi V, Forti G, Maggi M. Psychobiological correlates of extramarital affairs and differences between stable and occasional infidelity among men with sexual dysfunctions. J Sex Med. 2009;6:866–75.

    Article  PubMed  Google Scholar 

  37. Pasterski V, Hindmarsh P, Geffner M, Brook C, Brain C, Hines M. Increased aggression and activity level in 3- to 11-year-old girls with congenital adrenal hyperplasia (CAH). Horm Behav. 2007;52:368–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cohen-Bendahan CC, Buitelaar JK, van Goozen SH, Orlebeke JF, Cohen-Kettenis PT. Is there an effect of prenatal testosterone on aggression and other behavioral traits? A study comparing same-sex and opposite-sex twin girls. Horm Behav. 2005;47:230–7.

    Article  CAS  PubMed  Google Scholar 

  39. Ptok U, Barkow K, Heun R. Fertility and number of children in patients with Alzheimer’s disease. Arch Womens Ment Health. 2002;5:83–6.

    Article  CAS  PubMed  Google Scholar 

  40. Barha CK, Galea LA. Motherhood alters the cellular response to estrogens in the hippocampus later in life. Neurobiol Aging. 2011;32:2091–5.

    Article  CAS  PubMed  Google Scholar 

  41. Lund TD, Rovis T, Chung WC, Handa R. Novel actions of estrogen receptor-beta on anxiety-related behaviors. Endocrinology. 2005;2:797–807.

    Article  CAS  Google Scholar 

  42. Walf AA, Frye CA. Estradiol reduces anxiety- and depression-like behavior of aged female mice. Physiol Behav. 2010;99:169–74.

    Article  CAS  PubMed  Google Scholar 

  43. Chui HT, Christensen BK, Zipursky RB, Richards BA, Hanratty MK, Kabani NJ, Mikulis DJ, Katzman DK. Cognitive function and brain structure in females with a history of adolescent-onset anorexia nervosa. Pediatrics. 2008;122:426–37.

    Article  Google Scholar 

  44. Misra M, Katzman DK, Estella NM, Eddy KT, Weigel T, Goldstein MA, Miller KK, Klibanski A. Impact of physiologic estrogen replacement on anxiety symptoms, body shape perception, and eating attitudes in adolescent girls with anorexia nervosa: data from a randomized controlled trial. J Clin Psychiatry. 2013;8:e765–71.

    Article  Google Scholar 

  45. Gordon CM, Ackerman KE, Berga SL, Kaplan JR, Mastorakos G, Misra M, Murad MH, Santoro NF, Warren MP. Functional hypothalamic amenorrhea: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102:1413–39.

    Article  PubMed  Google Scholar 

  46. Kulkarni J, de Castella A, Smith D, Taffe J, Keks N, Copolov D. A clinical trial of the effect of estrogens in acutely psychotic women. Schizophr Res. 1996;20:247–52.

    Article  CAS  PubMed  Google Scholar 

  47. Kulkarni J, Riedel A, de Castella AR, et al. A clinical trial of adjunctive oestrogen treatment in women with schizophrenia. Arch Womens Ment Health. 2002;5:99–104.

    Article  CAS  PubMed  Google Scholar 

  48. Manji HK, Lenox RH. Ziskind-Somerfeld Research Award. Protein kinase C signaling in the brain: molecular transduction of mood stabilization in the treatment of manic depressive illness. Biol Psychiatry. 1999;46:1328–51.

    Article  CAS  PubMed  Google Scholar 

  49. Haskell SG, Richardson ED. The effect of raloxifene on cognitive function in postmenopausal women: a randomized clinical trial. Conn Med. 2004;68:355–8.

    PubMed  Google Scholar 

  50. Vercammen A, Skilletere AJ, Lenroot R, Catts SV, Weickert CS, Weickert TW. Testosterone is inversely related to brain activity during emotional inhibition in schizophrenia. PLoS One. 2013;8:e77496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Goldstein JA. Danazol and the rapid-cycling patient. J Clin Psychiatry. 1986;3:153–4.

    Google Scholar 

  52. Miller KK, Perlis RH, Papakostas GI, Mischoulon D, Losifescu DV, Brick DJ, Fava M. Low-dose transdermal testosterone augmentation therapy improves depression severity in women. CNS Spectr. 2009;12:688–94.

    Article  Google Scholar 

  53. Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, Burki RE, Ginsburg ES, Rosen RC, Leiblum SR, Caramelli KE, Mazer NA. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682–8.

    Article  CAS  PubMed  Google Scholar 

  54. Goldstat R, Briganti E, Tran J, Wolfe R, Davis SR. Transdermal testosterone therapy improves wellbeing, mood, and sexual function in premenopausal women. Menopause. 2003;10:390–8.

    Article  PubMed  Google Scholar 

  55. Fisher AD, Castellini G, Ristori J, Casale H, Cassioli E, Sensi C, Fanni E, Amato AM, Bettini E, Mosconi M, Dèttore D, Ricca V, Maggi M. Cross-sex hormone treatment and psychobiological changes in transsexual persons: two-year follow-up data. J Endocrinol Metab. 2016;11:4160–9.

    Google Scholar 

  56. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5). 2DSM-5. Washington DC: American Psychiatric Association; 2013.

    Book  Google Scholar 

  57. Fisher AD, Ristori J, Bandini E, Giordano S, Mosconi M, Jannini EA, Greggio NA, Godano A, Manieri C, Meriggiola C, Ricca V, Italian GnRH analogs study ONIG group, Dettore D, Maggi M. Medical treatment in gender dysphoric adolescents endorsed by SIAMS-SIE-SIEDP-ONIG. J Endocrinol Invest. 2014;37:675–87.

    Article  CAS  PubMed  Google Scholar 

  58. Fisher AD, Castellini G, Bandini E, Casale H, Fanni E, Benni L, Ferruccio N, Meriggiola MC, Manieri C, Gualerzi A, Jannini E, Oppo A, Ricca V, Maggi M, Rellini AH. Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria. J Sex Med. 2014;3:709–19.

    Article  CAS  Google Scholar 

  59. Fisher AD, Bandini E, Casale H, Ferruccio N, Meriggiola MC, Gualerzi A, Manieri C, Jannini E, Mannucci E, Monami M, Stomaci N, Delle Rose A, Susini T, Ricca V, Maggi M. Sociodemographic and clinical features of gender identity disorder: an Italian multicentric evaluation. J Sex Med. 2013;10:408–19.

    Article  PubMed  Google Scholar 

  60. Gorin-Lazard A, Baumstarck K, Boyer L, et al. Hormonal therapy is associated with better self-esteem, mood, and quality of life in transsexuals. J Nerv Ment Dis. 2013;201:996–1000.

    Article  PubMed  Google Scholar 

  61. Gorin-Lazard A, Baumstarck K, Boyer L, et al. Is hormonal therapy associated with better quality of life in transsexuals? A cross-sectional study. J Sex Med. 2012;9:531–41.

    Article  PubMed  Google Scholar 

  62. Colizzi M, Costa R, Todarello O. Transsexual patients’ psychiatric comorbidity and positive effect of cross-sex hormonal treatment on mental health: results from a longitudinal study. Psychoneuroendocrinology. 2014;39:65–73.

    Article  CAS  PubMed  Google Scholar 

  63. Gómez-Gil E, Zubiaurre-Elorza L, Esteva I, Guillamon A, Godas T, Cruz Almaraz M, Halperin I, Salamero M. Hormone-treated transsexuals report less social distress, anxiety and depression. Psychoneuroendocrinology. 2012;37:662–70.

    Article  CAS  PubMed  Google Scholar 

  64. Jones BA, Haycraft E, Murjan S, Arcelus J. Body dissatisfaction and disordered eating in trans people: a systematic review of the literature. Int Rev Psychiatry. 2016;28:81–94.

    Article  PubMed  Google Scholar 

  65. van de Grift TC, Cohen-Kettenis PT, Steensma TD, De Cuypere G, Richter-Appelt H, Haraldsen IR, Dikmans RE, Cerwenka SC, Kreukels BP. Body satisfaction and physical appearance in gender dysphoria. Arch Sex Behav. 2016;3:575–85.

    Article  Google Scholar 

  66. Fleming MZ, MacGowan BR, Robinson L, Spitz J, Salt P. The body image of the postoperative female-to-male transsexual. J Consult Clin Psychol. 1982;50:461–2.

    Article  CAS  PubMed  Google Scholar 

  67. Achermann JC, Hughes IA. Disorders of sex development. In: Kronenberg HM, Melmed S, Polonsky JS, Larsen PRXI, editors. Williams textbook of endocrinology, vol. 22. Philadelphia: Elsevier; 2008. p. 783–848.

    Google Scholar 

  68. Boada R, Janusz J, Hutaff-Lee C, Tartaglia N. The cognitive phenotype in Klinefelter syndrome: a review of the literature including genetic and hormonal factors. Dev Disabil Res Rev. 2009;15:284–94.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Bruining H, Swaab H, Kas M, Van Engeland H. Psychiatric characteristics in a self-selected sample of boys with Klinefelter syndrome. Pediatrics. 2009;123:e865–70.

    Article  PubMed  Google Scholar 

  70. Fisher AD, Castellini G, Casale H, Fanni E, Bandini E, Campone B, Ferruccio N, Maseroli E, Boddi V, Dèttore D, Pizzocaro A, Balercia G, Oppo A, Ricca V, Maggi M. Hypersexuality, paraphilic behaviors, and gender dysphoria in individuals with Klinefelter’s syndrome. J Sex Med. 2015;12:2413–24.

    Article  PubMed  Google Scholar 

  71. Ross JL, Roeltgen D, Stefanatos G, et al. Cognitive and motor development during childhood in boys with Klinefelter syndrome. Am J Med Genet A. 2008;146:708–19.

    Article  Google Scholar 

  72. Geschwind DH, Boone KB, Miller BL, et al. Neurobehavioral phenotype of Klinefelter syndrome. Ment Retard Dev Disabil Res Rev. 2000;6:107–16.

    Article  CAS  PubMed  Google Scholar 

  73. Simpson JL, Swerdloff RS, Samango-Sprouse CA, et al. Klinefelter syndrome. In: Cassidy SB, Allanson JE, editors. Management of genetic syndromes. 2nd ed. Hoboken: Wiley-Liss; 2004. p. 323–34.

    Google Scholar 

  74. Dhejne C, Van Vlerken R, Heylens G, Arcelus J. Mental health and gender dysphoria: a review of the literature. Int Rev Psychiatry. 2016;28:44–57.

    Article  PubMed  Google Scholar 

  75. Murad MH, Elamin MB, Garcia MZ, Mullan RJ, Murad A, Erwin PJ, Montori VM. Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes. Clin Endocrinol. 2010;72:214–31.

    Article  Google Scholar 

  76. Bockting WO, Goldberg JM. Guidelines for transgender care. Int J Transgenderism. 2006;9:3–4.

    Article  Google Scholar 

  77. Nuttbrock L, Hwahng S, Bockting W, Rosenblum A, Mason M, Macri M, Becker J. Psychiatric impact of gender-related abuse across the life course of male-to-female transgender persons. J Sex Res. 2009;1:12–23.

    Google Scholar 

  78. Auer MK, Hohne N, Bazzara-Castro MA, Pfister H, Fuss J, Stalla GK, et al. Psychopathologic profiles in transsexuals and the challenge of their special status among the sexes. PLoS One. 2013;10:78469.

    Article  CAS  Google Scholar 

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Fisher, A.D., Ristori, J., Maggi, M. (2018). Pharmachosexology: Use of Sex Hormones in Psychiatric Conditions. In: Jannini, E., Siracusano, A. (eds) Sexual Dysfunctions in Mentally Ill Patients. Trends in Andrology and Sexual Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-68306-5_19

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