Scientific Research Into Physical Causes Of Retarded Ejaculation
There are many other causes of ejaculatory disorders, especially surgery. Ejaculatory dysfunction has been reported in about 40% of men with bilateral sympathectomy at the L2 level. There is an even higher rate of emission failure in men who have surgery with high bilateral retroperineal lymphadenectomy.
Dysfunction of the sphincter of the bladder neck may occur after prostatectomy, which may lead to retrograde ejaculation into the bladder. Other conditions which can give rise to ejaculatory disorders include a history of disease and pelvic surgery (although of course one must be careful not to mistake the phenomena of orgasm without ejaculation for delayed ejaculation: this phenomenon may that be nothing more than retrograde ejaculation, where no ejaculation is observed because of the retrograde ejaculation, while orgasm occurs naturally and is succeeded by loss of erection).
Also, there are chronic medical conditions that can affect male sexual performance and orgasm. Angina, for example, is a strong suspect in this regard, while cigarette smoking can cause vascular insufficiency and decreasing levels of penile nitrous oxide.
As many men will know heavy consumption of alcohol or other recreational drugs may well inhibit the genital nervous and vascular system so that they do not operate correctly.
The most common medical conditions causing various forms of sexual difficulties are diabetes and high blood pressure - how to lower blood pressure is described here - and it's also well-known that various drugs which are available on prescription can induce male orgasmic disorder: these include Alpha and Beta adrenergic blockers, sympathetic nerve blockers, monoamine oxidase inhibitors, antidepressants, tricyclic antidepressants and SSRIs.
The Matter Of Brain Chemistry
Many studies have shown changes in brain chemistry - in serotonin levels, in fact - affect the delay before a man ejaculates. This implies that some men may actually have brain chemistry which predisposes them to ejaculate more slowly or quickly than average. (Though whether the change in brain chemistry is the cause or the effect of some other function remains open to speculation.) This of course opens the possibility of drug treatment for men who have had lifelong delayed ejaculation (male orgasmic disorder). At the moment, there are no drugs available for retarded ejaculation treatment, but research continues.
However, one area where drugs may play a part in a man's inability to ejaculate during sex is in causing the condition. There are many medications and non-prescription drugs, including alcohol, which can cause ejaculatory problems. In addition, the time taken for men to attain orgasm and release during climax increases with age. In the case of drugs which can cause delays in ejaculating or difficulties in reaching orgasm, there are often alternatives available.
Sometimes low levels of testosterone are implicated in the condition: in such cases, a full hormonal profile and check up by a qualified and competent andrologist is indicated.
As far as the treatment of delayed ejaculation is concerned, the first approach might be to investigate the possibility of changes in the man's drug regimen.
This might mean eliminating iatrogenic causes such as Alpha adrenergic blockers or antihypertensives, antidepressants, and antipsychotics. When antidepressants are implicated, switching to bupropion and mirtazapine may be helpful, as they have fewer side effects on the sexual system than SSRIs. Adjunctive therapies such as alpha sympathomimetrics may be helpful. Sildenafil and Imipramine may be effective in psychotropic-induced male orgasmic disorder.
Stimulation of the penis is required in most circumstances to achieve both emission and ejaculation. Efferent nerve impulses travel from the pudendal nerves until they reach the region of the upper lumbar spinal sympathetic nuclei. At this point the hypogastric nerve acts as a conduit for impulses which activate both secretions and the movement of sperm from the epididymis through the vas deferens, seminal vesicles and prostate to the base of the urethra. When the internal urethral sphincter closes and the external urethral sphincter relaxes, the semen is directed into the bulb at the base of the penis - this is the moment of emission.
But the mechanism of orgasm is one of the parts of the sexual process which is still far from understood. It involves central nervous system integration in response to various sexual stimuli, but emission, ejaculation, and orgasm are all associated with various other non-genital stimuli and responses in the body. For example, think of the involuntary contractions of the anal sphincter, the rapid breathing, the raised heart beat, or the elevation of blood pressure during sexual activity.
The somatomotor efferent branch of the pudendal nerve stimulates the bulbocavernous muscle into a series of rhythmic contractions, the effect of which is to force the semen through a narrowing of the urethra, producing a more or less powerful ejaculation of between 2 and 5 ml of semen. This is an involuntary action, but it involves an integration of both autonomic and somatic systems.
The network in the brain which controls the final output of all stimulation relating to ejaculation includes the posteromedial bed nucleus of the stria terminalis, along with the posterodorsal medial amygdaloid nucleus, and the parvicellular part of the subparafasicular thalamus.
It appears that the ejaculation reflex in man is mostly regulated by central serotonergic and dopaminergic systems while other neurotransmitters including acetylcholine, oxytocin, adrenaline and nitric oxide appear to have a secondary role.
There's evidence that serotonin 5HT exerts some kind of inhibitory role in the process of ejaculation through the brain's descending pathways. 5HT receptor subtypes A B and C have been associated with the modulating effect of serotonin on ejaculation.
Pharmacological manipulation of the serotonergic system has been undertaken in experimental rats, where SSRIs [selective serotonin re-uptake inhibitors] were the most effective compounds in the delaying of the ejaculation. Presynaptic 5HT1A receptors appear to be responsible for decreasing ejaculatory latency; postsynaptic 5H1B and 5H2C receptors appear to prolong ejaculatory latency.
In various animal models, dopamine levels measured in the medial preoptic area of the hypothalamus apparently progressively increased during sexual excitation and intercourse, while GABA receptor antagonists inhibited sexual behavior. Muscular contractions during the moment of ejaculation are, according to some research, affected by oxytocin.
All in all, therefore, with this relationship between serotonergic receptors and the effects that inhibit the sexual mechanism, and the effects that excite the sexual mechanism, the altered levels of 5HT, or varying receptor sensitivity in the central nervous system centers that modulate ejaculation, it's most likely that these altered levels of 5HT lie behind ejaculatory disorders. It's been suggested for example the serotonin has the capacity to suppress ejaculation by interrupting the effect of oxytocin.
However, despite all this research, the exact role and importance of various neurotransmitters in the etiology of delayed ejaculation is far from clear due to the multifactorial and extraordinarily complex nature of the male ejaculation reflex.
Transient sympathoadrenal activation during sexual activity which is associated with various increases in adrenaline and noradrenaline plasma levels have been reported as associated with male orgasm. And yet the association of vasopressin, luteinizing hormone, follicle stimulating hormone, growth hormone, cortisol and various other hormones to male orgasm all remain unclear.
Even though both oxytocin and prolactin levels are clearly observable as peaking immediately after the moment of orgasm, prolactin is a more reliable indicator of male orgasm.
So in the face of poor confirmation from various experiments of any hypothesis related to the mechanism of retarded ejaculation and how it may be treated, it follows that investigation has been limited, and the results of those studies which have been conducted are unclear.
Ejaculation distribution theory
Waldinger and his colleagues formulated a neurobiological theory on premature ejaculation and delayed ejaculation. They concluded that lifelong delayed ejaculation, and also premature ejaculation, are simply part of a normal biological variability of latency time (time between penetrating and ejaculation). Any sample of men will include some who ejaculate too soon, and some who always or almost always, show delayed ejaculation or inability to ejaculate at all. Lifelong delayed ejaculation is therefore a neurobiological variant found in the population, which may or may not cause psychological or psychosocial distress.
Studies on rats have tried to create hyposexual behavior by manipulating their level of sexual experience. 278 sexually inexperienced male rats were exposed to receptive females (in estrus) for 15 minutes: 23 showed no sexual activity at all; 211 displayed sexual activity, but failed to ejaculate; the average tie between penetration and ejaculation in the remaining rats was about ten minutes. Treatment with 5-HT1A receptor agonists - especially 8-OH-DPAT and flesinoxan - improved the sexual performance of these sexually inexperienced rats to levels almost similar to that of sexually experienced rats. In addition 2-adrenoceptor antagonists including yohimbine and idazoxan shortened the time to ejaculation time. Mos et al. also showed that male rats given 5-HT1A receptor agonists (flesinoxan, gepirone) were more sexually attractive to female rats in estrus than untreated males.
Hyposexual behavior in sexually naive and inactive rats can be reversed by the opioid receptor antagonist naloxone. Other work has shown that certain pharmacological compounds neuropeptides also have the ability to act as stimulants to copulatory behavior in sexually naive rats. The 5-HT1A receptor agonist 8-OH-DPAT is one of these compounds and clearly increases levels of sexual activity in rats that were previously sexually inactive .
Similarly, sildenafil (Viagra) and low doses of melatonin also have the capacity to reverse hyposexual behavior. All of this research suggests that specific neurobiological mechanisms are responsible for hyposexual behavior, at least in these sexually naive rats.
One of the neurotransmitters which is involved in ejaculation is oxytocin; it's produced mainly in the paraventricular nucleus of the hypothalamus, parts of which extend into the lumbosacral part of the spinal cord. Arletti and colleagues demonstrated that expression of oxytocin mRNA is less in the paraventricular nucleus of the hypothalamus of sexually naive and inactive rats, which in turn suggests that oxytocin plays some role in copulatory behavior. It is unclear exactly what this may be.
Opioids are other neuropeptides associated with the neurobiology of copulatory behavior; recent work suggests mRNA expression of pro-enkephalin and pro-dynorphin, and endogenous opioid octapeptide levels, are increased in the hypothalami of sexually inactive rats. It may be that hypothalamic endogenous opioid expression is responsible for differences in copulatory behavior, an idea which matches the suggestion that brain opioids inhibit sexual behavior.
In summary, some neurobiological substrates may be responsible for hyposexual behavior. This may also be true for men with delayed ejaculation and complete failure of ejaculation.
Oxytocin and brain peptides seem to play a small role in copulatory behavior, while serotonergic neurotransmission appears to be more significant. Treatment of male rats with 5-HT1A receptor agonists (8-OH-DPAT or flesinoxan) leads to shorter ejaculation latency times. So maybe lifelong delayed ejaculation is related to hypofunction of 5-HT1A receptors and/or hyperfunction of 5-HT2C receptors.
However, the improving effects of 5-HT1A receptor agonists, contrast with treatment with 5-HT2C receptor antagonists in men (nefazodone and mirtazapine), did not have any effect on ejaculation time. It seems that hyperfunction of the 5-HT2C receptor as a cause of delayed ejaculation is not proven.
But the researchers emphasize that nefazodone and mirtazapine are not considered as selective 5-HT2C antagonistic agents. Practically, experimental 5-HT1A receptor agonists like 8-OH-DPAT or flesinoxan accelerate ejaculation in male rats, but these agents are not available for human use. Based on rat research, the development of new and safe 5-HT1A receptor agonists can be advocated as a starting point for human clinical drug research in delayed ejaculation.
Nothing is known about the brain regions involved in delayed ejaculation and absence of ejaculation. A recent PET-scan study on absence of ejaculation was performed by Georgiadis and Holstege. 11 healthy male volunteers with anejaculation tried to achieve ejaculation in the PET-scan, but only about half of them managed to do so. However, successful ejaculation caused marked increase in cerebral blood flow in the meso-diencephalic transition zone and the cerebellum.
Those men who tried unsuccessfully to achieve ejaculation showed blood flow in the right orbitofrontal cortex, the left dorsal prefrontal cortex, and bilaterally in the anterior insula. By comparison, non-ejaculation blood flow involved more cortical activity than that associated with ejaculation, especially in the left temporal pole and most anterior amygdala, parts of the brain that have a role to play in vigilance and fear behavior. This may mean that higher levels of activity in the anterior temporal lobe are the cause of absence of ejaculation.
Delayed ejaculation treatment ]