Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents

Frontiers in Endocrinology

Volumn 5, Issue MAY, 2014, Pages

  Burke, Sarah M ^a,b   Cohen Kettenis, Peggy T ^a   Veltman, Dick J ^a   Klink, Daniel T ^a   Bakker, Julie ^a,b,c  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b NETHERLANDS INSTITUTE FOR NEUROSCIENCE   (Netherlands)

^c UNIVERSITY OF LIÈGE   (Belgium)

Author keywords

Androstadienone; Chemo signal; fMRI; Gender dysphoria; Hypothalamus; Puberty; Sex difference

Indexed keywords

ANDROSTA 4, 16 DIEN 3 ONE; STEROID; UNCLASSIFIED DRUG;

ADOLESCENT; ARTICLE; BRAIN FUNCTION; CENTRAL NERVOUS SYSTEM SENSITIZATION; CHILD; CONTROLLED STUDY; DEVELOPMENTAL STAGE; FEMALE; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENDER DYSPHORIA; GENDER IDENTITY; HETEROSEXUAL FEMALE; HETEROSEXUAL MALE; HUMAN; HYPOTHALAMIC ACTIVATION; HYPOTHALAMUS; IMAGE PROCESSING; MAJOR CLINICAL STUDY; MALE; NERVE STIMULATION; OLFACTORY STIMULUS; PERINATAL DEVELOPMENT; PSYCHOPHYSIOLOGY; PUBERTY; SEX DIFFERENCE; SEX DIFFERENTIATION; SEXUAL MATURATION;

EID: 84905444217     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2014.00060     Document Type: Article

References (55)

1. Kwan TK, Kraevskaya MA, Makin HL, Trafford DJ, Gower DB. Use of gas chromatographic-mass spectrometric techniques in studies of androst-16-ene and androgen biosynthesis in human testis; cytosolic specific binding of 5alpha-androst-16-en-3-one. J Steroid Biochem Mol Biol (1997) 60:137-46. doi: 10.1016/S0960-0760(96)00162-8
2. Nixon A, Mallet AI, Gower DB. Simultaneous quantification of five odorous steroids (16-androstenes) in the axillary hair of men. J Steroid Biochem (1988) 29:505-10. doi:10.1016/0022-4731(88)90185-9
3. Brooksbank BW, Cunningham AE, Wilson DA. The detection of androsta-4,16-dien-3-one in peripheral plasma of adult men. Steroids (1969) 13:29-50. doi:10.1016/S0039-128X(69)80058-9
4. Kwan TK, Trafford DJ, Makin HL, Mallet AI, Gower DB. GC-MS studies of 16-androstenes and other C19 steroids in human semen. J Steroid Biochem Mol Biol (1992) 43:549-56. doi:10.1016/0960-0760(92)90243-C
5. Brooksbank BW, Wilson DA, MacSweeney DA. Fate of androsta-4,16-dien-3-one and the origin of 3-hydroxy-5-androst-16-ene in man. J Endocrinol (1972) 52:239-51. doi:10.1677/joe.0.0520239
6. Gower DB, Ruparelia BA. Olfaction in humans with special reference to odorous 16-androstenes: their occurrence, perception and possible social, psychological and sexual impact. J Endocrinol (1993) 137:167-87. doi:10.1677/joe.0.1370167
7. Bensafi M, Brown WM, Khan R, Levenson B, Sobel N. Sniffing human sex-steroid derived compounds modulates mood, memory and autonomic nervous system function in specific behavioral contexts. Behav Brain Res (2004) 152:11-22. doi:10.1016/j.bbr.2003.09.009
8. Jacob S, McClintock MK. Psychological state and mood effects of steroidal chemosignals in women and men. Horm Behav (2000) 37:57-78. doi:10.1006/hbeh.1999.1559
9. Jacob S, Hayreh DJ, McClintock MK. Context-dependent effects of steroid chemosignals on human physiology and mood. Physiol Behav (2001) 74:15-27. doi:10.1016/S0031-9384(01)00537-6
10. Villemure C, Bushnell MC. The effects of the steroid androstadienone and pleasant odorants on the mood and pain perception of men and women. Eur J Pain (2007) 11:181-91. doi:10.1016/j.ejpain.2006.02.005
11. Bensafi M, Tsutsui T, Khan R, Levenson RW, Sobel N. Sniffing a human sex-steroid derived compound affects mood and autonomic arousal in a dose-dependent manner. Psychoneuroendocrinology (2004) 29:1290-9. doi:10.1016/j.psyneuen.2004.03.007
12. Bensafi M, Brown WM, Tsutsui T, Mainland JD, Johnson BN, Bremner EA, et al. Sex-steroid derived compounds induce sex-specific effects on autonomic nervous system function in humans. Behav Neurosci (2003) 117:1125-34. doi:10.1037/0735-7044.117.6.1125
13. Grosser BI, Monti-Bloch L, Jennings-White C, Berliner DL. Behavioral and electrophysiological effects of androstadienone, a human pheromone. Psychoneuroendocrinology (2000) 25:289-99. doi:10.1016/S0306-4530(99)00056-6
14. Lundstöm J, Lundström JN, Gonçalves M, Esteves F, Olsson MJ. Psychological effects of subthreshold exposure to the putative human pheromone 4,16-androstadien-3-one. Horm Behav (2003) 44:395-401. doi:10.1016/j.yhbeh.2003.06.004
15. Lundström JN, Olsson MJ. Subthreshold amounts of social odorant affect mood, but not behavior, in heterosexual women when tested by a male, but not a female, experimenter. Biol Psychol (2005) 70:197-204. doi:10.1016/j.biopsycho.2005.01.008
16. Wyart C, Webster WW, Chen JH, Wilson SR, McClary A, Khan RM, et al. Smelling a single component of male sweat alters levels of cortisol in women. J Neurosci (2007) 27:1261-5. doi:10.1523/JNEUROSCI.4430-06.2007
17. Parma V, Tirindelli R, Bisazza A, Massaccesi S, Castiello U. Subliminally perceived odours modulate female intrasexual competition: an eye movement study. PLoS One (2012) 7:e30645. doi:10.1371/journal.pone.0030645
18. Savic I, Berglund H, Gulyas B, Roland P. Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans. Neuron (2001) 31:661-8. doi:10.1016/S0896-6273(01)00390-7
19. Burke SM, Veltman DJ, Gerber J, Hummel T, Bakker J. Heterosexual men and women both show a hypothalamic response to the chemo-signal androstadienone. PLoS One (2012) 7:e40993. doi:10.1371/journal.pone.0040993
20. Chopra A, Baur A, Hummel T. Thresholds and chemosensory event-related potentials to malodors before, during, and after puberty: differences related to sex and age. Neuroimage (2008) 40:1257-63. doi:10.1016/j.neuroimage.2008.01.015
21. Dorries KM, Schmidt HJ, Beauchamp GK, Wysocki CJ. Changes in sensitivity to the odor of androstenone during adolescence. Dev Psychobiol (1989) 22:423-35. doi:10.1002/dev.420220502
22. Hummel T, Krone F, Lundström JN, Bartsch O. Androstadienone odor thresholds in adolescents. Horm Behav (2005) 47:306-10. doi:10.1016/j.yhbeh.2004.10.007
23. Koelega HS, Köster EP. Some experiments on sex differences in odor perception. Ann N Y Acad Sci (1974) 237:234-46. doi:10.1111/j.1749-6632.1974.tb49859.x
24. Schulz KM, Molenda-Figueira H, Sisk CL. Back to the future: the organizational-activational hypothesis adapted to puberty and adolescence. Horm Behav (2009) 55:597-604. doi:10.1016/j.yhbeh.2009.03.010
25. Sisk CL, Zehr JL. Pubertal hormones organize the adolescent brain and behavior. Front Neuroendocrinol (2005) 26:163-74. doi:10.1016/j.yfrne.2005.10.003
26. Berglund H, Lindström P, Dhejne-Helmy C, Savic I. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb Cortex (2008) 18:1900-8. doi:10.1093/cercor/bhm216
27. Berglund H, Lindström P, Savic I. Brain response to putative pheromones in lesbian women. Proc Natl Acad Sci U S A (2006) 103:8269-74. doi:10.1073/pnas.0600331103
28. Savic I, Berglund H, Lindström P. Brain response to putative pheromones in homosexual men. Proc Natl Acad Sci U S A (2005) 102:7356-61. doi:10.1073/pnas.0407998102
29. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Arlington, VA: American Psychiatric Association (2013).
30. Swaab DF, Garcia-Falgueras A. Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Funct Neurol (2009) 24:17-28.
31. van Goozen SH, Gooren LJG, Sanders G, Cohen-Kettenis PT, Slabbekoorn D. Organizing and activating effects of sex hormones in homosexual transsexuals. Behav Neurosci (2002) 116:982-8. doi:10.1037/0735-7044.116.6.982
32. Marantz S, Coates S. Mothers of boys with gender identity disorder: a comparison of matched controls. J Am Acad Child Adolesc Psychiatry (1991) 30:310-5. doi:10.1097/00004583-199103000-00022
33. Zucker KJ, Bradley SJ. Gender Identity Disorder and Psychosexual Problems in Children and Adolescents. New York, NY: The Guilford Press (1995).
34. Coolidge FL, Thede LL, Young SE. The heritability of gender identity disorder in a child and adolescent twin sample. Behav Genet (2002) 32:251-7. doi:10.1023/A:1019724712983
35. Gooren L. The biology of human psychosexual differentiation. Horm Behav (2006) 50:589-601. doi:10.1016/j.yhbeh.2006.06.011
36. Kreukels BPC, Cohen-Kettenis PT. Puberty suppression in gender identity disorder: the Amsterdam experience. Nat Rev Endocrinol (2011) 7:466-72. doi:10.1038/nrendo.2011.78
37. Delemarre-van de Waal HA, Cohen-Kettenis PT. Clinical management of gender identity disorder in adolescents: a protocol on psychological and paediatric endocrinology aspects. Eur J Endocrinol (2006) 155:S131-7. doi:10.1530/eje.1.02231
38. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ, Spack NP, et al. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab (2009) 94:3132-54. doi:10.1210/jc.2009-0345
39. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child (1970) 45:13-23. doi:10.1136/adc.45.239.13
40. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child (1969) 44:291-303. doi:10.1136/adc.44.235.291
41. Hummel T, Kobal G, Gudziol H, Mackay-Sim A. Normative data for the "Sniffin' sticks" including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. Eur Arch Otorhinolaryngol (2007) 264:237-43. doi:10.1007/s00405-006-0173-0
42. Kobal G, Klimek L, Wolfensberger M, Gudziol H, Temmel A, Owen CM, et al. Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol (2000) 257:205-11. doi:10.1007/s004050050223
43. Kobal G, Hummel T, Sekinger B, Barz S, Roscher S, Wolf S. "Sniffin' sticks": screening of olfactory performance. Rhinology (1996) 34:222-6.
44. Lemieux L, Salek-Haddadi A, Lund TE, Laufs H, Carmichael D. Modelling large motion events in fMRI studies of patients with epilepsy. Magn Reson Imaging (2007) 25:894-901. doi:10.1016/j.mri.2007.03.009
45. Brett M, Anton J, Valabregue R, Poline J-B. Region of interest analysis using an SPM toolbox [abstract]. Presented at the 8th International Conference on Functional Mapping of the Human Brain. Sendai (2002).
46. Makris N, Swaab DF, van der Kouwe A, Abbs B, Boriel D, Handa RJ, et al. Volumetric parcellation methodology of the human hypothalamus in neuroimaging: normative data and sex differences. Neuroimage (2013) 69:1-10. doi:10.1016/j.neuroimage.2012.12.008
47. Baroncini M, Jissendi P, Balland E, Besson P, Pruvo J-P, Francke J-P, et al. MRI atlas of the human hypothalamus. Neuroimage (2012) 59:168-80. doi:10.1016/j.neuroimage.2011.07.013
48. Lundström JN, Hummel T, Olsson MJ. Individual differences in sensitivity to the odor of 4,16-androstadien-3-one. Chem Senses (2003) 28:643-50. doi:10.1093/chemse/bjg057
49. Steensma TD, Biemond R, de Boer F, Cohen-Kettenis PT. Desisting and persisting gender dysphoria after childhood: a qualitative follow-up study. Clin Child Psychol Psychiatry (2011) 16:499-516. doi:10.1177/1359104510378303
50. Nieder TO, Herff M, Cerwenka S, Preuss WF, Cohen-Kettenis PT, De Cuypere G, et al. Age of onset and sexual orientation in transsexual males and females. J Sex Med (2011) 8:783-91. doi:10.1111/j.1743-6109.2010.02142.x
51. Steensma TD, McGuire JK, Kreukels BPC, Beekman AJ, Cohen-Kettenis PT. Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study. J Am Acad Child Adolesc Psychiatry (2013) 52:582-90. doi:10.1016/j.jaac.2013.03.016
52. Baum MJ, Keverne EB. Sex difference in attraction thresholds for volatile odors from male and estrous female mouse urine. Horm Behav (2002) 41:213-9. doi:10.1006/hbeh.2001.1749
53. Pierman S, Douhard Q, Balthazart J, Baum MJ, Bakker J. Attraction thresholds and sex discrimination of urinary odorants in male and female aromatase knockout (ArKO) mice. Horm Behav (2006) 49:96-104. doi:10.1016/j.yhbeh.2005.05.007
54. Lawrence AA. Sexual orientation versus age of onset as bases for typologies (subtypes) for gender identity disorder in adolescents and adults. Arch Sex Behav (2010) 39:514-45. doi:10.1007/s10508-009-9594-3
55. Gläscher, J. Visualization of group inference data in functional neuroimaging. Neuroinformatics (2009) 7:73-82. doi:10.1007/s12021-008-9042-x