The Role of Testosterone in the Sexual Function. Luiz Otavio Torres President Elect of ISSM Belo Horizonte - Brazil

Transcription

1 The Role of Testosterone in the Sexual Function Luiz Otavio Torres President Elect of ISSM Belo Horizonte - Brazil

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3 Hormones and Sexual Function Paraventricular Nucleus Stimuli visual Sexual Desire Melatonine MPOA Locus Cerulens PGN tactile auditive Dopamine Norepinephrine Oxitocine situational NO Spinal cord Erection Center T12 Simpatic ganglia Testosterone Erection Muscular Trophism Parassimpatic CC Flacidity Vascular Tone NO genic expression Simpatic and pudendal nerve CE (Scientific American.Illustration by John W. Karapelou 2000)

4 Testosterone - Erectile Function Eretogenic stimuli erotic image audiovisual tactile olfactory Cerebral cortex MPOA Inibitory stimuli anxiety fear depression Testosterone Spinal cord PRO-ERECTILE NEURAL SIGNAL

5 The Impact of Testosterone on Erection Stimulatory neurotransmitter Dopamine,NO,Oxytocin Noradrenaline (5HT 2C -Rez.) Serotonin(partly) alpha-msh (Melanocortin 2 u. 4 Rez. Vasopressin,ACTH Testosterone Endothel O 2 + L - Arginine + Parasympathetic ACH nerves + enos G -Protein Guanylatecyclase NO + Citrulline NANC nerve NO VIP Testosterone Sexual Stimulation Spinal erection center S2-S4 + Adenylatecyclase Testosterone Smooth muscle cell GTP 5-GMP cgmp ATP 3 5 -camp Phosphodiesterase 5 Inh. Sildenafil, Tadalafil, Vardenafil, other Testosterone 5

6 Actions of Testosterone in Sexual Function LEVEL OF ACTION LOCAL OF ACTION EFFECT DECREASE DESIRE Central Preoptic Anterior Hypothalamic area Libido Sexual Drive Desire Dysfunction EXCITEMENT Central Peripheral Bulge Corpora Cavernosa Nocturnal erections Erotic erections Erectile Dysfunction ORGASM EJACULATION Peripheral Prostate Seminal Vesicles Ejaculation Seminal volume Ejaculatory/ Orgasmic Dysfunction Morales a et al - ICSM 2004 Paris

7 Testosterone - Endothelial System -Androgen receptors in the vascular endothelium -Proliferation of smooth muscle and endothelial cels -Modulates the vascular physiology through endothelial dependent and independent mecanisms -Intraluminal injection of T relaxation of the coronary arteries -Reduce angina and miocardial isquemy induced by physical exercises -Reduce pro-trombotic factors and the development of the ateroma plaque -Low levels of testosterone is associated to the increase of coronary disease and AMI J Endocrinol 2013;217(3):47-71

8 Testosterone administration regulates Nitric Oxide syntesis in animal corpora cavernosa Morley JE and Perry III HM. Androgen treatment of male hypogonadism in older males. J Steroid Bioch Mol Biology. 2003; 85: Lugg JA, Rajfer J, Gonzalez-Cadavid NF. Dihydrotestosterone is the active androgen in the maintenance of nitric-oxide mediated penile erection in the rat. Endocrinology. 1995; 136: Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M, Orlando C, Vannelli GB, Aversa A, Natali A, Forti G, Jannini EA, Ledda F, Maggi M. Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology. 2004; 145:

9 Testosterone Erectile Function Structural changes in the penis -Studies in castrated animals -Reduction and apoptosis of the smooth muscles of the corpora cavernosa -Adipocyte accumulation in the sub tunical area -Decrease of the nervous fibers and mielinic sheets of the cavernous nerves -Decrease of neuronal and endothelial NOS expression -Decrease of the smooth muscle relaxation mediated by the NO -Decrease of the arterial influx to the corpora cavernosa -Increase of the answer to the alpha-adrenergic vasoconstriction mediators (Aversa A et al., Eur Urol 2004)

10 Changes in the rat penile smooth muscles Castration causes apoptosis T replacement promotes new DNA syntesis Shabsigh R World J Urol 15: (1997)

11 Effect of Castration and Androgen Substitution on Trabecular Smooth Muscle and Connective Tissue Content in the Corpus cavernosum Control Castrated + Vehicle Castrated + Testosterone Castrated + Estradiol Traish A et al. Endocrinol 1999;140(4):

12 Traish A et al. Endocrinol 1999;140(4):

13 Changes in the cc smooth muscles and conective tissue in rabbits Control Lupron 2 weeks. Lupron 8 weeks Traish A et al. J Androl 24(3): (2003)

14 Effect of Androgen Deprivation on the Ultrastructure of the Tunica albuginea in Rats Group A: Control rich, regularly arranged elastic fibers Group B: Castrated (4 weeks) elastic fibers replaced by collagenous fibers Shen Z-J Asian J Androl 1: (2003)

15 Testosterone Modulates the accumulation of adipocyte In the corpora cavernosa Control Castrated Traish A et al. J Androl 26(2): (2005)

16 Sham-operated rabbit Castrated rabbit Withdrawal of testosterone through castration results in apoptosis of cavernous smooth muscle cells and accumulation of adipocytes. These tissue architecture changes result in a decrease of cavernosal compliance with,in turn, increased venous outflow and ED. Traish,A. et al: J Androl. 2005,26,

17 Effect of testosterone deficiency in the cavernous nerves in rats

18 Increases Libido Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab. 1992; 75: Tan RS, Culberson JW. An integrative review on current evidence of testosterone replacement therapy for the andropause. Maturitas. 2003; 43: Hajjar RR, Kaiser FE, Morley JE. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab. 1997; 82: Jain P, Rademaker AW, McVary KT. Testosterone supplementation for erectile dysfunction: results of a meta-analysis. J Urol. 2000; 164:

19 Delayed ejaculation and Testosterone Evidences correlates low testosterone and delayed ejaculation Low T (< 300 ng/dl) men: 82 with delayed ejaculation - Controled factors: stress, SSRI, antidopaminergic drugs, prolactin, decreased libido of the patient and partner Corona et al J Androl 2008, Corona `et al JSM 2008; Corona et al Int J Androl 2010

20 TIMES2 TRT restores sexual symptoms of Hypogonodism Mean changes in the sexual desire domain Another domains at 12 months: Erectile Function (p=0.089) Orgasmic Function (p= 0.176) Satisfaction in the intercourse (p= 0.004) Sexual satisfaction in general (p= 0.045) Jones et al Diabetes Care 2011;34:828

21 Wang C et al. J Clin Endo Metab 2000; 85: Restores the Sexual Well Being

22 Desire, erections, sexual activity and satisfaction 1. Wang C, Cunningham G, Dobs A, 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:

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