uhh masturbation problem...?
Question:
Answers:
Some people simply can't hold an orgasm for very long, and others orgasm for several minutes on end. It's different for each person.
Though, the amount of sperm you ejaculate could be a problem. You may not be producing the average amount a normal male makes, and it may benefit you to see a doctor. Also, wearing tight pants and briefs can inhibite sperm production.
Other Answers:
give it 3days and it will have more sperm
cant help ya sry......2 points
Sucks to be you!!
Jonny, you seem to have posted far too many questions about this subject. Can you find anything else to think about?
I think your best bet is to go back to school and get some writing lessons. If you actually have barley coming out of you, I think you should go to the doctor
Go and see a doctor he will helpyou, it is not a serious problem
I would say stop doing it for a couple of days and it will be fine
yea wait between incidents and there will be more. If you are under say 16 then the volume will increase till you are 21.
Leave it 4 a week and you'll be surprised.
uhhhh take a "mastrubation vacation" you have got to find something else for your hands to do for 10 days like borad games, macramae, you take charge! your wennie is not the boss of you just tell himm you are sorry but you can't come out and play I am sure it will understand
Oh my! You have barley coming out of your weewee? You're a medical anomaly!
stop doing it so much! if you leave urself alone, the excitement will come back.
INTRODUCTION — The three major forms of male sexual dysfunction are erectile dysfunction, ejaculatory dysfunction and decreased libido. Erectile dysfunction is a common problem in men over the age of 40 due to hormonal abnormalities, medications, psychological problems, neurologic disease, or vascular insufficiency. Men with this disorder experience significant psychological distress which improves if treatment successfully restores erectile function [1]. Premature ejaculation (or rapid ejaculation) may be an even more common form of sexual dysfunction [2].
The treatment of male sexual dysfunction is reviewed here. Erectile physiology and the major causes of erectile dysfunction are discussed in detail elsewhere (See "Overview of male sexual dysfunction" and see "Evaluation of male sexual dysfunction"). Guidelines from the American Urological Association (AUA) have been published for the treatment of erectile dysfunction [3] and premature ejaculation [2]. A copy of these guidelines may be obtained by calling the AUA Health Policy Department at (410) 223-4367. The American Association of Clinical Endocrinologists has also issued treatment guidelines [4].
GENERAL PRINCIPLES — The first step in the treatment of male sexual dysfunction is to determine the etiology. Certain clues in the history and appropriate laboratory testing can usually establish the primary cause (show table 1). (See "Evaluation of male sexual dysfunction").
Therapy of men with erectile dysfunction is aimed at restoration of the two vital sexual functions: the capacity to acquire and sustain penile erections; and the reactivation of libido. Optimal treatment varies with the cause of the erectile dysfunction (show table 2A-2B):
Phosphodiesterase-5 (PDE-5) inhibitors, penile self-injection programs with vasoactive drugs, vacuum erection devices, or penile prostheses allow many men with vasculogenic, neurogenic, or psychogenic erectile dysfunction to acquire and maintain erections.
* For first-line therapy, we recommend the phosphodiesterase inhibitors because of their efficacy, ease of use, and favorable side effect profile. Sildenafil, vardenafil, and tadalafil appear to be equally effective, but tadalafil has a longer duration of action. (See "Phosphodiesterase-5 inhibitors" below). Phosphodiesterase inhibitors are contraindicated in men taking nitrates.
* For second-line therapy, we recommend consideration of penile self-injectable drugs, intraurethral alprostadil, and vacuum devices. (See "Penile self-injection" below and see "Vacuum-assisted erection devices" below).
* Surgical implantation of a penile prosthesis should be reserved for men who cannot use or who have not responded to first- and second-line therapies. (See "Penile prostheses" below).
* Testosterone replacement therapy should be the initial treatment for men with hypogonadism. (See "Testosterone treatment of male hypogonadism").
* Psychotherapy alone or in combination with psychoactive drugs may be helpful in men whose erectile dysfunction is caused by depression or anxiety. In addition, alpha adrenergic blocking agents such as yohimbine hydrochloride have enjoyed some popularity as a remedy for men with psychogenic erectile dysfunction. (See "Overview of male sexual dysfunction").
* In obese men with erectile dysfunction, weight loss and increased physical activity are associated with an improvement in erectile function in about one third of patients [5].
PHOSPHODIESTERASE-5 INHIBITORS — For men with erectile dysfunction, treatment options now include three phosphodiesterase-5 (PDE-5) inhibitors: sildenafil, vardenafil and tadalafil (show table 3). All act to increase intracavernosal cyclic GMP levels, and each one has been proven to be effective in restoring erectile function, allowing for satisfactory sexual intercourse in many men with erectile dysfunction.
Sildenafil — Sildenafil was the first orally administered treatment of proven efficacy for erectile dysfunction. Taken one hour before planned sexual intercourse, it is effective for a wide range of disorders causing erectile dysfunction. Nevertheless, it should not be prescribed before performing a systematic assessment of the cause of erectile dysfunction, including a history and physical examination and measurement of serum testosterone, prolactin, and TSH. (See "Evaluation of male sexual dysfunction"). The presence of potentially curable diseases may be missed with the indiscriminate prescription of this drug [6].
The rationale for the use of sildenafil and other PDE-5 inhibitors is based upon the role of nitric oxide-induced vasodilation (which is mediated by cyclic GMP) in initiating and maintaining an erection. (See "Overview of male sexual dysfunction", section on Role of blood flow and nitric oxide). Detumescence is associated with catabolism of cyclic GMP by type 5 phosphodiesterase. PDE-5 inhibitors act by blocking the latter enzyme and as a result increases both the number and duration of erections in men with erectile dysfunction [7].
Efficacy — In a dose-escalation study of 25 to 100 mg of sildenafil in 532 men with either organic (70 percent), psychogenic (11 percent), or mixed erectile dysfunction (18 percent), 69 percent of all attempts at sexual intercourse were successful in the men who took sildenafil compared to 22 percent of those who took placebo [8]. The mean number of successful attempts at intercourse each month was 5.9 with sildenafil versus 1.5 with placebo. Headache, flushing, and dyspepsia were the most common adverse effects, occurring in 6 to 18 percent of the men. All do not respond to the drug as well, however. Only 56 percent of diabetic men have improved erections with sildenafil [9]. (See "Erectile dysfunction in diabetes mellitus"). In men with prostate cancer who have undergone prostatectomy or radiation therapy, sildenafil appears to be effective in approximately 50 percent of patients [10], (more effective in those who had a nerve-sparing operation) [11]. (See "Radical prostatectomy for localized prostate cancer").
A man's sexual capability can be measured using the International Index of Erectile Function (IIEF). Survey scores of men with erectile dysfunction (ED) are significantly lower than normal men. IIEF scores remain low in placebo-treated men but the IIEF scores of sildenafil-treated men are comparable to normal healthy controls. This is true even for men who have multiple factors contributing to their ED [12].
In a quantitative meta-analysis of 27 trials in 6659 men with erectile dysfunction, a higher percentage of successful sexual intercourse was achieved with sildenafil compared with placebo (57 vs. 21 percent, respectively) [13].
In a study of healthy male volunteers without erectile dysfunction, sildenafil 100 mg caused no changes in seminal parameters or erectile function when compared to placebo [14]. Because sildenafil treatment is associated with a marked reduction in the post-ejaculatory refractory time, men are capable of having a second erection in a shorter time frame than was possible without this therapy.
The addition of exogenous testosterone to sildenafil therapy may be useful in men with serum total testosterone concentrations <400 ng/dL who do not respond to sildenafil alone. This was illustrated in a study of 75 such patients who were randomly assigned to receive daily testosterone gel (5 gm/day) or placebo in addition to sildenafil [15]. A greater improvement in erectile function (as measured by the IIEF) was observed in the testosterone-sildenafil group when compared with placebo. Although serum total and free testosterone concentrations increased in the testosterone-sildenafil group, no correlation was seen between testosterone levels and erectile function.
Dose — For maximum effectiveness, sildenafil should be taken orally about one hour before a planned sexual encounter. The initial dose should be 50 mg, and it should be reduced to 25 mg if side effects occur. If, on the other hand, it is well tolerated but the erectile response is not fully satisfactory, the dose can be increased to 100 mg. Each sildenafil pill costs about $9.00 retail.
Cardiovascular effects — Sildenafil is associated with a variety of cardiovascular effects, which are discussed in detail elsewhere. (See "Sexual activity in patients with heart disease", section on Sildenafil).
Summarized briefly:
* Sildenafil is a vasodilator that lowers the blood pressure by about 8 mmHg; this change typically produces no symptoms [16].
* The combination of sildenafil and nitrates can lead to severe hypotension (eg, more than 50/25 mmHg) [17] and syncope. As a result, sildenafil is contraindicated in patients taking nitrates of any form, regularly or intermittently. If a man who has taken sildenafil has an acute ischemic syndrome, nitrates should not be prescribed within 24 hours (or longer in patients with renal or hepatic dysfunction).
* Sildenafil has been associated with myocardial infarction and sudden death. However, since sexual activity is also associated with these complications, case reports of MI in association with sildenafil may have been unrelated to the drug. Consistent with this hypothesis are the results of extensive postmarketing surveillance, as well as a meta-analysis which have failed to demonstrate a significant association between sildenafil and cardiac events [13,16].
* Sildenafil does not appear to have adverse effects on coronary hemodynamics, even in men with either stable or severe coronary disease [18,19]. These data support the positions of the Second Princeton Consensus Panel and a consensus statement from the American College of Cardiology/American Heart Association that a PDE-5 inhibitor is safe for men with stable coronary artery disease who are not taking nitrates [20,21].
* The vasodilator properties of sildenafil may have an adverse effect in some patients with a hypertrophic cardiomyopathy; the decrease in preload and afterload can increase the outflow obstruction, culminating in an unstable hemodynamic state [22].
Precautions — There are no clinical data on the safety and efficacy of sildenafil in the following groups:
* Men who have had a myocardial infarction, stroke, or life-threatening arrhythmia within the last six months
* Men with resting hypotension (<90/50 mmHg) or hypertension (>170/110 mmHg)
* Men with cardiac failure or coronary artery disease causing unstable angina
The manufacturer suggests caution when prescribing sildenafil to these groups of men. A consensus statement from the American College of Cardiology/American Heart Association published in January 1999 presented recommendations about the use of sildenafil in men with cardiovascular disease [20]. The statement concluded that sildenafil was clearly contraindicated in men taking nitrates. Other men in whom it is potentially hazardous include those who have:
* Active coronary ischemia (eg, positive exercise test) who are not taking nitrates
* Heart failure and borderline low blood pressure or low volume status
* A complicated, multidrug, antihypertensive drug regimen
* Patients taking drugs that prolong the half-life of PDE-5 inhibitors by blocking CYP3A4; on the other hand, drugs that induce CYP3A4, such as rifampin and phenytoin, can be expected to reduce the effectiveness of these drugs.
Men who are considering sildenafil therapy should be questioned regarding exercise tolerance; resumption of sexual activity after a prolonged period of inactivity is analogous to beginning a new exercise regimen. Sildenafil can be considered in men who are participating in aerobic activities that are roughly equivalent in energy expenditure to sex. If such activity cannot be documented, more formal testing of exercise tolerance (eg, exercise treadmill testing) should be considered. Sexual activity in patients with heart disease is reviewed in detail elsewhere. (See "Sexual activity in patients with heart disease").
Alpha adrenergic antagonists, which are commonly used for the treatment of benign prostatic hyperplasia, may cause symptomatic hypotension when taken in combination with PDE-5 inhibitors [23]. Current labeling recommends that sildenafil doses above 25 mg should not be taken within four hours of an alpha-blocker.
Side effects — Side effects associated with sildenafil are related to its vasodilatory properties and are similar to those induced by nitrates. These include headache, lightheadedness, dizziness, flushing, distorted vision, and, in some cases, syncope. In the meta-analysis described above, adverse events with sildenafil included flushing, headaches, dyspepsia, and visual disturbances in 12,11, 5, and 3 percent, respectively [13].
Visual effects — Although sildenafil acts by inhibiting type 5 phosphodiesterase, it can affect the retina via weak inhibition of type 6 phosphodiesterase, which is required for the transformation of light into electrical signals. In a brief report of five normal men, a single 100 mg dose of sildenafil caused changes in the electroretinogram one hour later that were completely reversible at six hours [24]. There were no changes in visual acuity, visual fields, or visual-evoked potentials.
Sildenafil also causes blue vision in approximately 3 percent of men. This effect lasts two to three hours and disappears spontaneously.
Rare cases (23 cases since 1998) of non-arteritic anterior ischemic optic neuropathy (NAION) have been reported in men taking sildenafil and tadalafil [25]. Most of these cases occurred in men with underlying autonomic or vascular risk factors. NAION shares a number of risk factors with erectile dysfunction: age over 50, hypertension, dyslipidemia, and diabetes. Therefore, it is unclear whether NAION in these patients is due to their underlying vascular risk factors, anatomic defects, or use of sildenafil. However, the United States Food and Drug Administration has ordered that warnings be added to labeling for sildenafil, tadalafil, and vardenafil to reflect this potential risk [26].
The long-term effects of sildenafil on visual function are unknown. At this time, monitoring of visual function does not appear to be necessary in the average man without retinal disease [27].
Although there are no clinical data on the safety and efficacy of sildenafil in men with retinitis pigmentosa (a minority of whom have genetic disorders of retinal phosphodiesterase), the manufacturer recommends caution in these patients.
Drug interactions — Sildenafil should be avoided in patients taking drugs that can prolong the half-life of sildenafil by blocking CYP3A4 (including erythromycin, ketoconazole, protease inhibitors, and grapefruit juice); on the other hand, drugs that induce CYP3A4 such as rifampin and phenytoin can be expected to reduce the effectiveness of a dose of sildenafil (see "Genetic determinants of drug metabolism").
Recreational use — Sildenafil is commonly obtained without a prescription by men without erectile dysfuntion, and this type of use may have serious health consequences. In a systematic review of published studies, sildenafil use among homosexual men was associated with sexual risk behavior, and risk of sexually transmitted diseases, including HIV infection [28]. Little is known about the consequences of recreational use in heterosexual men.
Vardenafil and tadalafil — Vardenafil (Levitra) and tadalafil (Cialis) are newer, more selective and more potent phosphodiesterase inhibitors.
Vardenafil — Vardenafil is now FDA approved and is available as a 10 and 20 mg dose [29]. Although there are no direct comparison studies, vardenafil appears to be as effective as sildenafil [30-32]. The following observations illustrate both efficacy and potential concerns:
* In a trial of 805 men ages 57 to 78 with erectile dysfunction of various etiologies randomly assigned to receive vardenafil 5, 10, or 20 mg or placebo as needed for six months, vardenafil was more effective than placebo for improving penetration (64 to 80 versus 50 percent, respectively) and maintenance of erections (50 to 67 versus 32 percent, respectively) [32]. Similar results were noted in a second large, randomized trial [33].
* Vardenafil is also more effective than placebo for men with erectile dysfunction due to diabetes mellitus [34] or nerve-sparing radical prostatectomy [35] (See "Erectile dysfunction in diabetes mellitus" and see "Radical prostatectomy for localized prostate cancer".
* High-fat, but not moderate-fat meals, may lower vardenafil's peak serum concentration by approximately 18 percent, and delay its absorption by one hour [36].
* A slight prolongation of the QT interval may occur, but this is not thought to be clinically important [37]. However, vardenafil should not be used in men with congenital QT prolongation or in those taking antiarrhythmics drugs such as quinidine, procainamide, amiodarone, or sotalol. (See "Acquired long QT syndrome").
* Side effects are similar to those seen with sildenafil, and include headache, flushing, and rhinitis, in 13, 10, 10 and 5 percent, respectively [32,34]. In one trial, side effects decreased over time [32]. Changes in color vision (blue vision) have not been reported thus far [29]. Issues related to sexual activity in men with coronary heart disease are similar to those with sildenafil. (See "Sexual activity in patients with heart disease").
In summary, vardenafil appears to be as effective as sildenafil with no evidence of a more rapid onset of action or other clinical advantages (show table 3). Like sildenafil, vardenafil is contraindicated in men taking concurrent nitrates.
Package labeling for vardenafil had initially listed concurrent use of alpha-blockers as a contraindication. However, the labeling has been revised to state that patients should be stable on alpha-blocker therapy prior to initiating vardenafil (which should be started at the lowest recommended dose). In patients already taking vardenafil, alpha-blocker therapy should be started at the lowest dose possible [38].
Tadalafil — Tadalafil has a different chemical structure than sildenafil and vardenafil [39]. Although there are no direct comparison studies, tadalafil also appears to be as effective as sildenafil but has a longer duration of action (show table 3) [40,41]. Tadalafil is approved in Europe, the United States, and many other countries. The recommended starting dose is 10 mg, with 5 and 20 mg options available depending on efficacy and tolerability [42]. Food does not interfere with its absorption (show table 3) [43].
Efficacy is illustrated by the following observations:
* In an integrated analysis of randomized trials in 1112 men with erectile dysfunction receiving 2.5, 5, 10, or 20 mg of tadalafil or placebo, 75 percent of intercourse attempts were successful in the tadalafil group compared with 32 percent with placebo [44].
* In a second study in 348 men, 59 percent of intercourse attempts were successful at 36 hours with tadalafil (20 mg) compared with 28 percent with placebo [40].
Side effects — Side effects are similar to those seen with sildenafil and vardenafil with headache, dyspepsia, flushing, and rhinitis occurring in 8 to 14, 5 to 10, 4 to 6, and 5 percent, respectively [40,44]. In one study, back pain occurred in six percent of patients taking the 20 mg dose [42]. In general, the pain occurred 12 to 24 hours after dosing, was mild, and resolved within 48 hours. Visual side effects have not been described.
Drug interactions — Like sildenafil and vardenafil, tadalafil is contraindicated in men taking concurrent nitrates. Tadalafil is also contraindicated in men taking concurrent alpha adrenergic antagonists (with the exception of tamulosin 0.4 mg/day) [45,46].
In spite of its longer 1/2 life, the time course of nitrate interaction with tadalafil does not appear to be prolonged [47]. However, it has been suggested that nitrates should be avoided for at least 48 hours after the last tadalafil dose [48]. Other issues related to sexual activity in men with coronary heart disease are similar to those with sildenafil. (See "Sexual activity in patients with heart disease").
Excessive alcohol intake (5 or more drinks) in combination with tadalafil administration may potentiate the hypotensive effect of tadalafil [48].
Use of potent CYP3A4 inhibitors should be avoided as described above for sildenafil. (See "Drug interactions" aboveSee "Drug interactions" above).
Vision — Rare case reports of nonarteritic anterior ischemic optic neuropathy have been described with the PDE-5 inhibitors, prompting the United States Food and Drug Administration to require revised labeling to reflect this potential risk [26]. (See "Visual effects" above).
In addition to PDE-5, an extensive family of phosphodiesterases exist, some with defined and others with not yet clarified roles in human physiology. PDE-6 is present in the retina and has a role in color vision. The PDE-5 inhibitor in sildenafil cross-reacts with the retinal PDE-6 and accounts for the transient "blue vision" side effect reported in a small percentage of sildenafil-treated men. Tadalafil does not appear to disrupt PDE-6 so blue vision has not been reported with this medication.
Reproductive effects — However, tadalafil does show some cross reactivity with PDE-11, an enzyme that is present in the testes and pituitary, but the physiologic significance of this enzyme is unclear. Tadalafil does not appear to disrupt any aspect of normal pituitary or testicular function [49]. This was illustrated in a study of 421 men over age 45 who were randomly assigned to receive placebo (n=101) vs. tadalafil 10 mg (n=103), or placebo (n=106) vs. tadalafil 20 mg (n=111) daily for six months. During this interval, when compared to placebo, six months of daily administration of tadalafil caused no change in sperm concentration, sperm count, motility or morphology and did not alter serum LH, FSH or testosterone concentrations.
Dietary supplements — The FDA has issued a warning to consumers not to purchase or consume the following dietary supplements: SIGRA, STAMINA Rx and STAMINA Rx for Women, Y-Y, Spontane ES, and Uroprin [50]. These supplements claim to increase sexual stamina, confidence, and performance and claim to contain prescription-strength doses of tadalafil. A similar FDA warning was issued for Vinarol tablets, a supplement that contains sildenafil [51]. The concern is that patients who take nitrates for cardiovascular disease may experience a drastic lowering of blood pressure if these supplements are consumed.
Comparisons — All PDE-5 inhibitors allow men to have erections after appropriate sexual stimulation but differ in the onset of action as well as duration of effectiveness (show table 3). Tadalafil differs in two ways. Its absorption is less affected by high fat meals and alcohol and it has a longer duration of action. Sildenafil has the longest safety record of the three drugs.
With sildenafil and vardenafil men are advised that maximum effectiveness is achieved by taking the tablet on an empty stomach (high fat meals and alcohol appear to delay the absorption of both drugs) and then wait at least an hour before attempting sexual intercourse. Tadalafil can be taken without regard to meals.
The period of effectiveness for a single dose of sildenafil or vardenafil is four hours. Men with erectile dysfunction may have an erection in response to sexual stimulation for up to 36 hours after a single tadalafil dose [40].
Concomitant treatment with alpha adrenergic antagonists (used to alleviate symptoms associated with benign prostatic hyperplasia) is contraindicated (due to potential hypotension with combination therapy), with the exception of tamsulosin, which may be used safely with tadalafil [45].
In one international multi-center double-blind crossover study comparing patient preference for sildenafil 50 mg or tadalafil 20 mg, 215 men (mostly sildenafil naïve men) with erectile dysfunction age 65 and younger were randomized to receive each medication for four weeks with an intervening one week washout period before switching to the other medication [52]. The following results were seen:
* Men reported a similar number of sexual intercourse episodes; 2334 with tadalafil and 2233 with sildenafil.
* At the end of the study, 66.3 percent of men expressed a preference for tadalafil and 33.7 percent for sildenafil as a treatment for their erectile dysfunction.
* The interval between dosing and sexual intercourse differed. On average sildenafil-treated men had sex 2.2 hours after dosing well within the 4 hour window of opportunity stipulated on the label whereas tadalafil-treated men were able to maintain efficacy but were able to delay sexual intercourse for 5.5 hours after dosing.
Summary — All three PDE-5 inhibitors: sildenafil, vardenafil and tadalafil work to sustain levels of cyclic GMP within the penile corpora cavernosae to allow men with erectile dysfunction to achieve erections in response to appropriate sexual stimuli. Side effect profiles are similar; only rarely do men with erectile dysfunction discontinue treatment because of side effects.
Men who take nitrates should not take any PDE-5 inhibitor. Alpha adrenergic antagonists are contraindicated (due to potential hypotension with combination therapy) with the exception of tamsulosin, which may be used safely with tadalafil [45]. (See "Sexual activity in patients with heart disease").
Duration of action that separates one PDE-5 inhibitor from another. Sildenafil and vardenafil are effective as early as 30 minutes and up to 4 hours after dosing whereas tadalafil is effective as early as 16 minutes after and up to 36 hours after dosing.
Sildenafil and vardenafil must be taken on an empty stomach, while tadalafil can be taken without regard to food.
PENILE SELF-INJECTION — Intrapenile injection therapy with alprostadil (prostaglandin E1, Caverject), papaverine, or alprostadil with papaverine and phentolamine (Tri-Mix) have all been used for purposes of inducing erection.
The sympathetic nervous system normally maintains the penis in a flaccid or non-erect state. All of these vasoactive drugs, when injected into the corpora cavernosae, inhibit or override sympathetic inhibition to encourage relaxation of the smooth muscle trabeculae within the penile erectile bodies. The ensuing onrush of blood engorges the penile corpora cavernosae sinusoidal spaces with sufficient pressure to compress the emissary veins that normally drain blood from the penis. The combination of accelerated arterial inflow and impeded venous outflow from the corpora cavernosae creates an erection (show figure 1).
Considerable education is required for men to become facile with this form of therapy. Under the guidance of urologists men are trained in sterile methods and the proper technique for inserting an insulin syringe with a 26 gauge needle through the shaft of the penis and injecting the vasoactive agent into one corporeal body (show figure 2). The cross circulation of the penile corpora allows medication injected into one penile corporeal body to diffuse over to the contralateral side so that a full, firm erection can be expected within a few minutes after intrapenile installation of the drug [53,54].
Specific drugs — In the early days of penile self-injection therapy, papaverine proved to be more reliable than phentolamine in producing an erection. Papaverine is a parenteral vasodilator with marginal efficacy in peripheral vascular disease, while phentolamine is an alpha-adrenergic blocker used for hypertensive crises in pheochromocytoma. (See "Clinical presentation and diagnosis of pheochromocytoma").
Alprostadil was originally introduced to maintain the patency of the ductus arteriosus before definitive cardiac surgery could be undertaken. When it became apparent that it was effective in a penile self-injection program, the pharmaceutical company making alprostadil was granted approval by the Food and Drug Administration in the United States to market alprostadil under the name Caverject as a treatment for erectile dysfunction. In comparison, the purveyors of papaverine and phentolamine never promoted, and indeed warned against, using their medications for penile self-injection. Nevertheless, alprostadil and papaverine remain popular as monotherapy, and all three drugs can be given together.
The efficacy and safety of a program of at-home intrapenile alprostadil injections were then investigated in a six-month study [55]. Six hundred and eighty three men with vasculogenic, neurogenic, psychogenic, and mixed causes of erectile dysfunction entered the trial and 471 (69 percent) completed the trial. The reasons for drop out included penile pain, lack of efficacy, loss to follow-up, dislike of self injection, and other problems. Sexual activity, recorded as sexual intercourse or masturbation, was reported by 551 men over the six-month period. A total of 11,223 instances of sexual intercourse and 701 masturbatory episodes occurred after 13,762 intrapenile alprostadil injections. This pattern of sexual activity was deemed to be satisfactory by 87 percent of the men completing the trial and 86 percent of their partners.
Attrition rate — Despite the relatively high success rate, there is a very high attrition rate with self-injection when used long-term, suggesting that it may not be satisfactory treatment for many men.
Side effects — The major side effect of intrapenile alprostadil therapy is penile pain, occurring in 50 percent. Pain was the side effect most often cited by men who discontinued therapy.
Priapism, or a prolonged erection lasting more than four to six hours, is a medical emergency often requiring immediate urologic attention to evacuate blood clogged within the corpora cavernosae [56]. Prolonged erections occur in 6 percent of men who use intrapenile alprostadil and about 11 percent of those who use intrapenile papaverine.
Lower doses should be used in men with neuropathic erectile dysfunction (due to spinal cord injury or multiple sclerosis), due to their risk of priapism.
One study evaluated the effects of prolonged priapism [57].
* Most priapism that lasted 36 hours could be treated successfully by puncture and alpha-adrenergic drugs without any fibrosis of the corpora cavernosa.
* After 48 hours, glandulocavernosal shunts were required to achieve detumescence. All the men developed fibrosis of the corpora cavernosa and all but one were unable to continue with the injections of vasoactive drugs.
Papaverine injected into the corpora cavernosae may escape into the general circulation and can be hepatotoxic; abnormal liver function tests have been reported in men using this drug for penile self-injection [58]. In contrast, alprostadil is metabolized within the corpora and does not adversely affect the liver.
Intraurethral alprostadil — Intraurethral administration of alprostadil (MUSE) provides a less invasive alternative to intrapenile injection. The efficacy of intraurethral alprostadil was evaluated in a double-blind, placebo-controlled trial in 1511 men with chronic erectile dysfunction from a variety of organic causes [59]. Two-third of these men responded to intraurethral alprostadil with an erection sufficient for intercourse; these men were then randomly assigned to therapy with either alprostadil or placebo. Successful intercourse on at least one occasion was much more likely with alprostadil (65 versus 19 percent with placebo). Among the men who responded to alprostadil, 7 of 10 applications were followed by successful intercourse.
After insertion of the alprostadil into the urethra, the penis should be massaged for up to one minute to ensure equal distribution in the corpora cavernosae.
Systemic effects were uncommon, and complications such as priapism and penile fibrosis were less common than after alprostadil given by penile injection. The 19 percent response rate in the placebo group suggests that psychogenic factors were responsible for the sexual dysfunction, since placebo injections do not induce erections in solely organic causes of impotence.
VACUUM-ASSISTED ERECTION DEVICES — Several mechanical devices have been developed which utilize vacuum pressure to encourage increased arterial inflow and occlusive rings to discourage venous egress from the penile corpora cavernosae. A certain amount of mechanical dexterity is required to use these devices effectively, but once men become comfortable with using the vacuum and restraining rings they can create an erection sufficient for vaginal penetration and sexual intercourse (show figure 3) (show figure 4). They cannot, however, ejaculate externally because the occlusive rings that prevent venous drainage also compress the penile urethra sufficiently to prevent seminal fluid from reaching and traversing the urethral meatus.
Vacuum devices successfully create erections in as many as 67 percent of patients. Satisfaction with vacuum-assisted erections has varied between 25 and 49 percent. As an example, one prospective study evaluated 18 men by questionnaire at six months: 16 (89 percent) were able to attain satisfactory erections, and the overall satisfaction rate was 83 percent [60]. Sixteen of the eighteen men found the device easy to use.
PENILE PROSTHESES — Enthusiasm for drug and penile injection therapy has greatly reduced reliance on surgical implants of penile prostheses as treatment for men with erectile dysfunction. This form of therapy remains a viable option for those men who do not respond to sildenafil and find penile injection or vacuum erection therapy distasteful. There are two general types of prostheses: malleable rods and inflatable prostheses.
Side effects include those related to the anesthesia, local wound infections, and mechanical failure necessitating surgical removal and reimplantation of a new functioning prosthesis.
OTHER THERAPIES
Psychotherapy and psychoactive medications — Psychological counseling, including the use of sensate focus exercises by both partners, can be helpful when the man is suffering from performance anxiety. This is usually best accomplished by referral to a certified sexual therapy counselor.
Erectile dysfunction is also a common symptom of depression and potency is usually restored as psychotherapy or antidepressant drugs alleviate the depression. However, many of the newest and most effective antidepressant drugs of the serotonin reuptake inhibitor class (eg, fluoxetine, sertraline, paroxetine) decrease both libido and erectile function [61]. On the other hand, trazodone, imipramine, and desipramine can cause delayed or retarded ejaculation, a "side effect" that may actually be beneficial for men suffering from premature ejaculation.
Yohimbine — By blocking presynaptic alpha-2-adrenergic receptors, yohimbine increases cholinergic and decreases adrenergic tone, changes that should theoretically be effective in men with psychogenic erectile dysfunction. Although a rich folk lore has imbued yohimbine with mystical aphrodisiacal properties, it has limited clinical effectiveness.
Optimal results are achieved when yohimbine use is restricted to men with psychogenic erectile dysfunction [62,63]. As an example, two double-blind, placebo-controlled studies evaluated 101 men with psychogenic erectile dysfunction [62]. Erectile function and sexual intercourse resumed in 37 percent of men treated with yohimbine (5.4 mg TID) within three days to three weeks of starting therapy; only 15 percent of placebo-treated men had a comparable response.
In contrast, a randomized, double-blind study of 29 men with erectile dysfunction of unclear etiology but no known endocrine or psychologic cause showed no difference between yohimbine and placebo; in both groups almost half improved [64]. A virtual lack of response was also noted in 20 men with erectile dysfunction due to arterial insufficiency and cavernous venous leakage who were treated with either a combination of yohimbine and isoxsuprine or pentoxifylline [65].
A meta-analysis reviewed this confused set of data on the efficacy of yohimbine [66]. Seven randomized controlled trials of reasonable quality were found and evaluated; the investigators concluded that there was enough evidence to recommend a trial of yohimbine as initial therapy (odds ratio: 3.9).
In practice, the prompt onset of action in "responders" has encouraged physicians to consider a trial of yohimbine in men with apparent psychogenic erectile dysfunction. Treatment is continued only in those who respond and also tolerate the drug's side effects, which include dizziness, flushing, nausea, and headache.
Yohimbine should be used with caution in patients with heart disease because of its cardiovascular side effects, including tachycardia and the potential for hypertension. (See "Sexual activity in patients with heart disease").
Androgen replacement therapy — If sexual dysfunction is associated with hypogonadism, testosterone can be replaced with one of several testosterone replacement preparations. Each of these preparations has its own advantages and disadvantages. (See "Testosterone treatment of male hypogonadism" for a discussion of the different preparations and the goals of therapy).
Role of vascular surgery — For an erection to occur blood must flow through a network of arteries all branching from the iliac artery and then on to smaller tributaries ending at the helicene arteries that feed the corpora cavernaosae. During moments of sexual excitation blood flows into the corpora cavernosae under such high pressure that if first causes penile swelling (tumescence) and then compresses the emissary veins that normally drain blood form the corpora cavernosae creating a rigid erection. Any condition that compromises arterial flow to the genital area can cause impotence by a "failure to fill" whereas premature egress of venous blood out of the emissary veins would set the stage for a "failure to store" form of erectile dysfunction.
Surgical techniques have been devised to alleviate arterial occlusions and correct "failure to fill" and also shore up sagging veins in men when "failure to store" seemed to be the root cause of their sexual dysfunction. Although these surgical procedures had enjoyed some popularity in the past, long-term sexual outcomes have been quite poor, with the exception of young patients with traumatic arterial lesions [67,68].
Melanocortin receptor agonists — Melanocortin receptor agonists, which act on the central nervous system rather than the vascular system, are being developed as a possible new therapy for erectile dysfunction. PT-141, an intranasal preparation, appears to be effective as monotherapy or in combination with PDE-5 inhibitors [69,70]. However, significant side effects, including flushing and nausea, may limit its clinical utility. This agent is neither approved for use or commercially available.
PREMATURE EJACULATION — Premature ejaculation (or rapid ejaculation) is defined as an inability to control ejaculation so that both partners enjoy sexual intercourse. Approximately 20 percent of men complain of premature ejaculation, most of whom have no underlying physical abnormality [71]. Nonpharmacologic therapy such as the "pause and squeeze" technique has achieved variable success [71], but drug therapy has proved quite useful.
Several psychoactive drugs can cause delayed or retarded ejaculation, and some have been evaluated for the treatment of premature ejaculation. In one double-blind study, 37 potent men ages 19 to 70 years who complained of premature ejaculation were randomly assigned to receive the selective serotonin reuptake inhibitor (SSRI) sertraline (50 mg/day) or placebo [72]. The mean ejaculatory latency time before treatment in both groups was 0.3 minutes and the mean interval after four weeks of treatment was 0.5 minutes in the placebo group and 3.2 minutes in the sertraline group, a significant difference. In a subsequent open-label phase of the study, 20 of 29 men (67 percent) were able to discontinue the drug after a mean of seven months and maintain a mean ejaculatory latency time greater than four minutes. Other SSRIs also appear to be effective [73,74].
Intermittent use of SSRIs may be as effective as continuous use. This issue was examined in a study of 26 men with premature ejaculation who were randomly assigned to receive paroxetine (20 mg) or placebo as needed three to four hours before planned intercourse [75]. The mean ejaculatory latency time was significantly greater in the paroxetine group compared with placebo after four weeks (3.2 versus 0.45 minutes). In a second phase of the study involving 42 men, treatment with paroxetine daily for three weeks prior to using it on an as needed basis improved ejaculatory control compared to men who only used the drug only as needed.
An additional SSRI, dapoxetine, also appears to be effective, based upon reports of completed Phase III trials [76].
The tricyclic antidepressant clomipramine is useful and possibly more effective than SSRIs in prolonging the interval from intromission to ejaculation. In one study of 36 men with premature ejaculation, four weeks of treatment with either placebo, fluoxetine, sertraline, or clomipramine resulted in increased ejaculation time from 46 seconds (placebo) to 2.27 minutes (fluoxetine), 4.27 minutes (sertraline), and 5.75 minutes (clomipramine) [77]. However, significantly more side effects, most notably dry mouth, occurred in patients treated with clomipramine.
One small trial suggested that sildenafil may be superior to clomipramine and SSRIs for premature ejaculation [78], but this has not been confirmed in larger studies.
RECOMMENDATIONS
Erectile dysfunction — For men with erectile dysfunction, we recommend the following:
* For first-line therapy, we recommend the phosphodiesterase inhibitors because of their efficacy, ease of use, and favorable side effect profile (Grade 1A). Sildenafil, vardenafil, and tadalafil appear to be equally effective, but tadalafil has a longer duration of action. (See "Phosphodiesterase-5 inhibitors" above).
* Phosphodiesterase inhibitors are contraindicated in men taking concurrent nitrates.
* We suggest that alpha adrenergic antagonists not be used concurrently with sildenafil or vardenafil (due to potential hypotension with combination therapy), with the possible exception of tamsulosin (0.4 mg/day), which appears to be safe when taken with tadalafil (Grade 2B). (See "Phosphodiesterase-5 inhibitors" above).
If the physician and patient choose to use PDE-5 inhibitors with alpha-blockers, we suggest that in patients on stable alpha-blocker therapy, PDE-5 inhibitors should be initiated at the lowest possible dose. In patients already taking an optimized dose of PDE-5 inhibitor, alpha-blocker therapy should be initiated at the lowest possible dose.
* We suggest that sildenafil and vardenafil be taken on an empty stomach, while tadalafil may be taken without regard to food.
* There are several second line therapies that have been shown to be effective: penile self-injectable drugs, intraurethral alprostadil, and vacuum devices. We suggest choosing among these options based upon patient preference. (Grade 2B) (See "Penile self-injection" above and see "Vacuum-assisted erection devices" above).
* We suggest that surgical implantation of a penile prosthesis be reserved for men who cannot use or who have not responded to first- and second-line therapies. (Grade 1B). (See "Penile prostheses" above).
* We recommend androgen replacement therapy only in men with documented hypogonadism (Grade 1A). (See "Androgen replacement therapy" above). (See "Testosterone treatment of male hypogonadism" and see "Decline in testicular function with aging").
Premature ejaculation
* We suggest selective serotonin reuptake inhibitors (SSRIs) as first-line therapy, and clomipramine as second-line therapy for men with premature ejaculation. (Grade 2B). These recommendations are consistent with AUA guidelines [2].
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Read a good book. When you turn 14 the problem may go away. You might want to sit down with your mom and explain your problem to her.
Put the dick down. Give the little guy a rest
dang, the well has been drained dry. give it time to build back up.
Use your other hand, it is like having an affair. Or even better sit on your hand until it is numb, then turn it around the other way. It will be like someone else is doing it.
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