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Learn More. Delayed ejaculation DE is an uncommon and a challenging disorder to treat. It is often quite concerning to patients and it can affect psychosocial well-being. Here we reviewed how DE is treated pharmacologically.

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We also highlighted specific settings where drugs could be introduced to medical practice. There are a of drugs to treat patients with DE including: testosterone, cabergoline, bupropion, amantadine, cyproheptadine, midodrine, imipramine, ephedrine, pseudoephedrine, yohimbine, buspirone, oxytocin, and bethanechol. Although there are many pharmacological treatment options, the evidence is still limited to small trials, case series or case reports. Review of literature showed that evidence level 1 Double blind randomized clinical trial studies were performed with testosterone, oxytocin, buspirone or bethanechol treatment.

It is concluded that successful drug treatment of DE is still in its infancy.

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The clinicians need to be aware of the pathogenesis of DE and the pharmacological basis underlying the use of different drugs to extend better care for these patients. Various drugs are available to address such problem, however their evidence of efficacy is still limited and their choice needs to be individualized to each specific case. In DSM-5 definition the condition must persist for a minimum duration of approximately six months with no specific duration of ejaculation latency. The condition is only a problem if it causes ificant distress for the patient or his partner.

In most cases, the diagnosis is made by self-report of the individual. Of all the male sexual dysfunctions, DE is the least understood, least common and least studied 2. This condition can be lifelong primary or acquired secondary. Premature cumshot reddit it may be global, that is, occurring in all sexual scenarios or situational, occurring only in specific sexual scenarios e. DE was shown to be associated with ificant reduction in health-related quality of life as well as self-esteem, anxiety, and depression and has been linked to reduced sexual satisfaction and relationship dissatisfaction and discord.

Proposed etiological factors include many medical, psychological and lifestyle factors 2 - 4. DE is not easy to treat because it is poorly understood 25.

Treatment should be etiology specific, and may include patient and their partner psychosexual therapy, drug therapy or integrated treatment. Drug treatment of DE includes many agents with varying degrees of success.

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A variety of drugs are identified for potential use in this condition. These drugs include testosterone, cabergoline, bupropion, amantadine, cyproheptadine, yohimbine, bethanechol, buspirone and others. However, no drugs have been approved by regulatory agencies for this indication. There is a consensus that DE is still a poorly understood disorder with inconsistent practice patterns seen among members of the SMSNA.

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Here, we reviewed how DE is treated pharmacologically. Moreover, ificant effects of small effect size are observed indicating elevated T levels in Premature cumshot reddit ejaculation PEand decreased T levels in DE patients. This effect demonstrated linear function of severity of ejaculatory dysfunction, so that patients with the most severe PE displayed the highest T values, and those patients with the most severe DE display the lowest T levels Similarly, nonificant difference in the composite Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form score was reported at week among androgen-deficient DE patients.

These negative might be an accurate reflection of reality and androgen deficiency is not the sole contributor to DE or they may be related to small sample size, short intervention period, and below threshold level of serum T required for ejaculatory function which is not yet known. Further studies are awaited. The rationale for a pharmacological approach to treating DE by cabergoline [a dopamine DA agonist on D2 receptors] came from the following observations: I DA has been recognized Premature cumshot reddit a pro-sexual neurotransmitter 1314 ; II DA agonists have been demonstrated to facilitate both animal 15 and human sexual behavior 16 ; III acute changes in the normal physiological levels of prolactin may also modify sexual motivation and function 17 ; IV increased prolactin concentrations by protirelin anterior pituitary gland stimulator administration produced ificantly longer ejaculation latency during the first sequence of sexual activity in healthy men, whereas, cabergoline-induced hypoprolactinemia ificantly enhanced all parameters of sexual drive and function, including ejaculation latency 17 ; and V cabergoline has been shown to activate the 5-HT 2B agonists receptors Activation of 5-HT 2B receptors may have effects on the ejaculation depending on the dose of the agonist Research on cabergoline for treatment of DE is hard to find.

A retrospective study presented at the annual meeting of the American Urological Association 20 evaluated the efficacy of cabergoline 0. The mean age of the patients was 63 whereas the mean duration of therapy for non-responders and responders was and days, respectively.

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However, the duration of therapy and the concomitant testosterone replacement therapy were associated with ificant response to treatment. In another retrospective study, Kacker et al. The authors treated these men on the basis of high-normal or mildly elevated prolactin mean Although these studies are promising in male anorgasmia, it is still uncertain if this drug will do the same in DE.

On the other hand, ejaculation is the expulsion of semen to outside involving both emission and the ejaculation proper a physical process. Usually the two conditions occur simultaneously in men 21 There is weak scientific evidence to suggest that cabergoline could be beneficial for some cases of delayed orgasm. Large-scale randomized controlled trials are necessary to further define the Premature cumshot reddit of the drug in DE apart from hyperprolactinemia.

However, special note must be taken that the drawbacks of cabergoline treatment include a higher risk of cardiac valve regurgitation and heart failure 23 due to activation of 5-HT2B receptors on valvular interstitial cells which is mitogenic 18increasing valve leaflet area and causing the poor valve closure. Longer treatment duration and higher dose of cabergoline is associated with these risks These side effects have never been demonstrated in episodic small dosing for sexual dysfunction. Bupropion is an atypical antidepressant belonging to the chemical class of aminoketones.

It is known as a DA and norepinephrine NE reuptake inhibitor used as smoking Premature cumshot reddit and antidepressant drug with a lower incidence of male sexual dysfunction. The rationale for using bupropion in DE comes from the following observations: I it has been shown that chronic bupropion administration at high doses alters the function of the spinal generator for ejaculation SGE in rats 24 ; II bupropion produces concentration- dependent increases in the contractile response to nerve stimulation in the rat vas deferens and ificantly increases the pressor response to noradrenaline suggesting facilitatory action of the ejaculatory reflex 25 ; III in vitro bupropion increases by eight-fold the NE potency in inducing contractions of the epididymal duct from untreated rats.

The ability of bupropion to enhance epididymal duct contractions to NE is due to its action as a NE transporter blocker as bupropion did not change duct contraction to methoxamine 26 ; IV bupropion has been demonstrated to induce premature ejaculation in 46 years old man after the use of mg bupropion per day for depression and premature ejaculation disappeared two weeks after stopping of bupropion 2728 ; and V bupropion showed prosexual effects when compared with the other antidepressants and no patient taking bupropion complained of delayed orgasm Most of the studies have noted that bupropion is not only as effective as other antidepressants but has the advantage of a lower impact on the sexual function.

Other studies have found that bupropion can even enhance sexual function in certain individuals In men treated for depression, DE and orgasmic dysfunction are the most ificant sexual complications The DE and anorgasmia with antidepressants have been attributed to increased serotonergic tone. This occurs due to suppression of ejaculation at the level of the hypothalamus Noradrenergic tone on the other hand stimulates ejaculation, which concurs with the finding that noradrenergic antidepressants such as bupropion have no or milder degree of sexual dysfunction as compared with selective serotonin re-uptake inhibitors SSRIs.

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There have been few reports 34 - 36 on the use of bupropion in DE among non-depressed men. Modell et al. Side effects such as insomnia, anxiety, irritability and headache were generally mild and transient occurred with greater frequency on the higher dose and in no case necessitated drug discontinuation.

Abdel-Hamid and Saleh 34 reported on bupropion therapy in a series of 19 lifelong DE men. There was also a ificant improvement in the intercourse satisfaction and the orgasmic domains of IIEF and depression score from baseline.

The authors concluded that bupropion-SR in a daily dosage of mg seemed to be of limited benefit in about of 1 fourth of lifelong DE patients. Bidaki et al. Although laboratory tests showed primary hypogonadism high level of LH and low T levelT undecanoate 25 mg weekly IM treatment did not result in improved DE. The authors reported that the sexual dysfunction had resolved three days after stopping bupropion. Although preliminary clinical data seem to suggest that bupropion has beneficial clinical effects in certain DE patients, there is not sufficient scientific Premature cumshot reddit to suggest that it could stand alone as a drug therapy for all patients with DE.

Further studies are needed. Amantadine hydrochloride is a weak glutamatergic antagonist that works by inhibiting the N-methyl-D-aspartate NMDA receptor, binding to it to avoid its excessive excitation by the glutamate neurotransmitter. It is also used for treating Parkinsonism, extrapyramidal symptoms and many other disorders It possesses DA enhancing activity by facilitating presynaptic DA release and inhibiting DA reuptake post-synaptically.

Based on the principle that increasing DA neurotransmission may enhance sexual function, amantadine-treated male rats showed a higher sexual response and decreased ejaculation latency time than vehicle-treated rats 40 - The primary site of action of this drug is possibly supraspinal because amantadine-induced seminal emissions were impaired by spinal cord transection On the other hand, Devaangam et al. The effects of amantadine on the human ejaculatory or orgasmic functions are conflicting.

Reported effective doses have ranged between — mg taken either on a daily or as-needed basis. Shrivastava et al. Amantadine was given in divided doses of mg twice daily and mg daily. There were no other side effects or drug interactions reported.

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Fifty three percent of these patients were originally complaining of orgasmic delay or anorgasmia. In this study, one patient on amantadine discontinued it secondary to depression, which resolved within 48 hr of discontinuation.

There is insufficient evidence to recommend amantadine for treatment of DE. Cyproheptadine is a piperidine derivative first-generation antihistamine. Cyproheptadine also has mild anticholinergic and antiserotonergic properties possibly through blocking 5-HT 1A and 5-HT 2A receptors Animal data suggested that cyproheptadine potentiates the prejunctional inhibitory effect of 5-HT and attenuates its stimulatory effect in the rat and guinea-pig vas deferens 4950 suggesting peripheral effects.

Additionally, it facilitates sexual behavior of the male rat possibly through antiserotonergic effects Moreover, cyproheptadine as a 5-HT 2A antagonist is usually recommended and is the most widely used antidote in the treatment of serotonin syndrome 5253 suggesting its efficacy as an antiserotonergic agent. The mechanism of antidepressants-induced DE and delayed orgasm is thought to involve stimulation of post synaptic 5-HT 2A and 5-HT 2C receptors by the increased synaptic levels of serotonin Antidepressants that antagonize these particular 5-HT receptors subtypes, such as mirtazapine and nefazodone, have a lower propensity to cause DE The prosexual effects of cyproheptadine are likely due to the antiserotonergic properties of the drug, rather than its antihistaminic effects, because diphenhydramine an antihistaminic is ineffective in treating sexual dysfunction 46 Several case reports and case series showed efficacy of cyproheptadine in reversal of DE or anorgasmia supposed to be caused by antidepressants 57 - 63monoamine oxidase inhibitors 64 or Premature cumshot reddit Effective doses range from 2—16 mg.

The drug is effective when taken either on an as-needed basis 1—2 hours before planned intercourse or on a daily basis nightly before bed time. The mean duration of treatment with cyproheptadine was 2.

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