Will post some snippets from the book later. I already see a potential reason why some of the personal treatments here work like they do. POIS might be neurosomatic.
Edit: Some snippets about
Testosterone:
Androgens such as
testosterone increase the secretion of dopamine, probably by decreasing the activity of the dopamine transporter. Ritalin and cocaine also have this action. Androgens also increase DA by interacting with NO.
The amino acid taurine inhibits the dopamine transporter and maywork somewhat like Ritalin. Taurine is an agent I have tried on several of my patients. It did not enhance dopamine effects but may augment lamotrigine in some individuals.
In rats that are
testosterone deficient, the density of tyrosine hydroxylase (TH)-immunopositive axons in the prefrontal cortex increases. Tyrosine hydroxylase converts tyrosine to dopa and is usually the ratelimiting enzyme in the biosynthesis of the catecholamines. The dysregulation of TH is attenuated by supplementing rats with
testosterone. The effect is mainly on dopamine and not norepinephrine.
Testosterone depletion produces a dopamine hyperinnervation in the prefrontal cortex in an attempt to compensate for decreased production of dopamine.
I have stopped using nitroglycerin as much. Too many patients have migraine headaches, and nitric oxide has been found to cause this disorder. With no history of severe headaches, I can opt to try it (one-half of a 0.3 mg tablet). It either works or not. It sometimes acts as an NMDA agonist since it is a retrograde messenger. Those that respond to nitroglycerin will often benefit from
testosterone, oxytocin, and agonists of DA, NE, and glutamate, all of which act in the MPOA to produce arousal and orgasm.
I start
testosterone gel at 10 mg/ml, particularly in women with decreased libido if they fail on transdermal estrogen. Their
testosterone levels are usually very low.
Perhaps the most relevant aspect of the neuroregulatory aspects of gonadal steroids in neurosomatic disorers is that “estradiol enhances and
testosterone attenuates novelty stress-stimulated increases in c-Fos mRNA in the hippocampus, with presumed consequent alterations in the transcription regulatory effects of c-Fos” (Roca CA et al., 1999). Until recently, I have been reluctant to use antiestrogen therapy in women except in treatment-refractory bipolar disorder (Goldstein JA, 1986). I have used
testosterone only in men who respond to nitroglycerin, since NO increases DA in the medial preoptic area of the brain. I may be liberalizing its use in transdermal treatment trials, however. When effective, it markedly increases alertness.
When men have a good response to nitroglycerin, I try transdermal
testosterone, which has an effect in 30 to 60 minutes or less. If it works, they feel much more energetic.
Testosterone induces the secretion of NO, which in turn increases DA in the medial preoptic area (Du J, Hull EM, 1999), which is the area of the brain that determines an individual’s response to sexual stimuli. I shall discuss the sexual response in neurosomatic disorders in the section on oxytocin. A much lower dose of transdermal
testosterone can have a similar effect on women.
The situation in which synaptic fatigue is most obvious is that of sexual arousal and ejaculation in the male with a neurosomatic disorder. Some males relapse after ejaculation. A few relapse, but in a different, milder way, after sexual arousal. Arousal seems to depend on activation of the medial preoptic area by
testosterone, which facilitates NO synthase. NO increases the secretion of DA in the POA, which, as has been seen, is associated with anticipation of reward. Arousal can be augmented by dextroamphetamine, which also increases DA, particularly in the NAc. Lesions of the MPOA in animals decrease sexual behavior. Sexual arousal, causing increased DA secretion, can cause relapse. Ejaculation is related to the actions of NE and oxytocin.
If the patient is hypertensive, anxious, has ADHD, or experiences nightmares, guanfacine would be a good choice. If perimenopausal or low in
testosterone, hormonal therapy would be helpful. Such patients usually have a good response to nitroglycerin, the active form of which is nitric oxide. Orgasm centrally requires estrogen or
testosterone, NO, OXT, and norepinephrine, plus a little dopamine acting atD1 receptors. Arousal requiresDA, OXT,
testosterone, and NO.
Testosterone induces NO synthesis, which then stimulates DA release in the medial preoptic nucleus, which facilitates arousal and penile erection. Oxytocin is required for penile erection.
Some articles posted earlier on the website regarding PE, NO, DA and Testosterone:Stimulation of dopamine autoreceptors elicits “premature ejaculation” in ratsRelevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors treatment on premature ejaculation: decreased nitric oxide is associated with premature ejaculationTestosterone Induces Molecular Changes in Dopamine Signaling Pathway Molecules in the Adolescent Male Rat Nigrostriatal Pathway
