|Year : 2007 | Volume
| Issue : 2 | Page : 110-112
Abstracts from current literature: Erectile dysfunction
Anitha Iyer, Archana Sharma, YS Marfatia
Department of Skin and VD, Medical College and SSG Hospital, Vadodara, Gujarat, India
Y S Marfatia
Department of Skin and VD, Medical College and SSG Hospital, Vadodara - 390 001, Gujarat
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Iyer A, Sharma A, Marfatia Y S. Abstracts from current literature: Erectile dysfunction. Indian J Sex Transm Dis 2007;28:110-2
|How to cite this URL:|
Iyer A, Sharma A, Marfatia Y S. Abstracts from current literature: Erectile dysfunction. Indian J Sex Transm Dis [serial online] 2007 [cited 2020 Aug 13];28:110-2. Available from: http://www.ijstd.org/text.asp?2007/28/2/110/39019
New treatment options for erectile dysfunction: Pharmacologic and nonpharmacologic options
Erectile dysfunction is a medical condition that influences the sexual life of millions of men and women worldwide. Due to a large number of drugs currently available, the therapy of erectile dysfunction has changed profoundly in the recent decades. The pharmacologic options are divided into initiators versus conditioners and central or peripheral acting drugs. Besides intraurethral and intracavernous application of prostaglandin E(1) [PGE(1), peripheral initiator] - a transdermal application still in clinical testing, there are drugs for oral application. PGE(1), the vasoactive drug used widely, was replaced by sildenafil in first-line therapy. PGE(1), administered intracavernosally or intraurethrally, is highly effective with success rates up to 90%, but the attrition rate due to personal inconvenience remains significant. Yohimbine is known as a central amplifier of erection and is useful in psychogenic and mild organic erectile dysfunction. Apomorphine, a central initiator of erection, amplifies erectile response as a central dopamine agonist in mild and moderate erectile dysfunction and starts acting 15-20 min after sublingual application. The phosphodiesterase type 5 (PDE-5) inhibitors - sildenafil, vardenafil and taladafil - are peripheral conditioners. Sildenafil, the most distributed oral agent worldwide, should be taken orally 60 min before sexual intercourse in combination with sexual stimulation. Sildenafil shows a high efficacy-safety profile with success rates for all etiologies between 50% and 80%. Paralleling nitrate-containing medication is an absolute contraindication. Vardenafil, another selective PDE-5 inhibitor with potentially higher selectivity and efficacy as compared to sildenafil, was just approved. The data from clinical trials show the same adverse events and success rates as sildenafil. Taladafil, just launched as well, amplifies erectile function for up to 24 h, allowing the patient to engage in sexual activity for this period. Adverse events and success rates resemble those of the other two substances. If medical treatment fails, there are nonpharmacologic options such as the vacuum constriction device and penile implants. The vacuum device is a safe and effective option for well-selected patients. Penile implants, especially the inflatable ones, completely imitate the physiologic erection. Due to recent research, infection rates and mechanical failures were minimized. Therefore, penile implant surgery is well accepted by patients and their partners. Despite this wide variety of options, therapy of erectile dysfunction should be performed in an individually adapted way. The patient's exact history, physical examination, collaboration of medical disciplines and choice of therapy can offer all patients the possibility to achieve or regain a satisfying sexual life.
Sperling H, Lümmen G, Schneider T, Rübben H. Herz 2003 Jun;28(4):314-24.
Novel indications for phosphodiesterase type 5 inhibitors
Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Hence, PDE5 inhibitors promote vasodilative effects by enhancing intracellular cGMP levels. Three PDE5 inhibitors - sildenafil, vardenafil and taladafil - have been approved for the treatment of 'erectile dysfunction' (ED). All three show excellent effectiveness regarding ED therapy, but differ from one another with respect to their pharmacokinetic properties. Recent experimental studies and clinical trials indicate that PDE5 inhibitors are also effective in the treatment of various other diseases such as pulmonary arterial hypertension (PAH), Raynaud's disease, gastrointestinal disorders and stroke, and furthermore exert cardioprotective effects. This review describes the cardiovascular safety of PDE5 inhibitors and provides an overview of the current literature regarding potential novel indications.
Rosenkranz S, Caglayan E, Erdmann E. Med Klin (Munich) 2007 Aug;102(8):617-30.
Combined use of androgen and sildenafil for hypogonadal patients unresponsive to sildenafil
The study was conducted to investigate the therapeutic effect of androgen on hypogonadal patients unresponsive to sildenafil alone. In total, 32 hypogonadal patients with erectile dysfunction (ED), who initially had inadequate response to sildenafil (100 mg), were chosen. Oral testosterone undecanoate (Restadol, 80 mg, bid or tid) alone was supplied for 2 months; if patients could not achieve satisfactory erection, combined use of testosterone and sildenafil was continued thereafter. Total testosterone (TT), free testosterone (FT) and the parameters of the International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS) and uroflow rate (UFR) were assessed. Eleven patients (34.3%) achieved satisfactory erectile function after testosterone replacement only. Another 12 (37.5%) patients experienced satisfactory intercourse after combined therapy. Serum TT and FT levels significantly increased after the use of testosterone alone. However, no statistical differences were demonstrated for IPSS or UFR. In conclusion, one-third of hypogonadal patients with ED who failed to respond to sildenafil responded to testosterone alone, another third responded to sildenafil again after normalization of testosterone. Thus, in hypogonadal patients with ED, androgen supplementation is the first-line therapy. If patients are unresponsive to androgen alone or sildenafil alone, combined use may improve erectile function and enhance the therapeutic effect of PDE-5 inhibitors.
Hwang TI, Chen HE, Tsai TF, Lin YC. Int J Impot Res. 2006 Jul-Aug;18(4):400-4. Epub 2006 Jan 5.
Testosterone therapy can enhance erectile function response to sildenafil in patients with PADAM : A pilot study
Recent studies suggest a direct relationship between free testosterone and cavernous vasodilatation. Some men with erectile dysfunction (ED) associated with PADAM (partial androgen deficiency in ageing men) might possibly benefit from testosterone undecanoate therapy (TRT). The objective of the study was to determine the efficacy of testosterone undecanoate in facilitating the erectile response and patient satisfaction with sildenafil in men 40-70 years old with PADAM symptoms. This prospective study included 40 patients recruited after a sildenafil therapeutic trial. Total testosterone and sex hormone binding globulin (SHBG) were measured to calculate the free androgen index. Prostate-specific antigen (PSA) was measured and repeated 2 months after treatment. A rating score was used for PADAM symptoms, and the five-point abbreviated version of the International Index of Erectile Function (IIEF-5) was used to assess erectile function. Men failing to respond to sildenafil were randomized into two groups receiving sildenafil plus continuous TRT (Group 1ST) and TRT (Group 1T) alone. Men partially responding to sildenafil were randomized into two groups receiving sildenafil plus continuous TRT for 2 months (Group 2ST) and sildenafil alone (Group 2S). Treatment efficacy was assessed by analysis of between-group differences. Groups 1T, 2S and 2ST showed significant improvement in PADAM score ( P < 0.05, Wilcoxon match pairs test). Patients receiving both sildenafil plus continuous TRT (Groups 1ST and 2ST) showed significant improvement in IIEF-5 score ( P < 0.5, paired t -test). No significant changes in serum levels of PSA were detected (paired t -test). We conclude that TRT appears to be beneficial and safe in facilitating the erectile response and patient satisfaction with sildenafil in men with PADAM syndrome. Androgen supplementation should be carried out cautiously with careful monitoring to avoid possible adverse effects.
Shamloul R, Ghanem H, Fahmy I, El-Meleigy A, Ashoor S, Elnashaar A, Kamel I. Sex Med 2005 Jul;2(4):559-64.
Hormonal supplementation and erectile dysfunction
The role of testosterone on sexual desire is well established. However, the effects of low testosterone levels in the pathophysiology of erectile mechanism in humans remain unclear. Recent evidence indicates that approximately 10-20% of men with erectile dysfunction (ED) have abnormalities, raising up to 35% over the age of 60. It is now clear that sexual desire and erectile function in humans are both responsive to androgens, probably at different threshold values. In fact, different degrees of testosterone deficiency may determine a sequence of molecular penile events leading to reduced capacity of penile smooth muscles and endothelial cells of relaxation, without greatly affecting sexual desire. Moreover, androgens may directly control the expression and activity of phosphodiesterase type 5 in human corpus cavernosum. In some selected men with total testosterone <10-13 nmol/L and/or free testosterone <200-250 pmol/L, androgen supplementation may improve therapeutic efficacy of phosphodiesterase type 5 inhibitor. For ageing men with partial androgen deficiency (PADAM) who failed first-line oral treatment, and in whom androgens are not contraindicated, a combination of testosterone and phosphodiesterase type 5 inhibitors may be considered to improve erectile function and improve the quality of life.
Aversa A, Isidori AM, Greco EA, Giannetta E, Gianfrilli D, Spera E, Fabbri A. Eur Urol. 2004 May;45(5):535-8.
Comparing vardenafil and sildenafil in the treatment of men with erectile dysfunction and risk factors for cardiovascular disease: A randomized, double-blind, pooled crossover study
Data from head-to-head clinical trials of phosphodiesterase type 5 (PDE5) inhibitors are scarce, making it difficult for clinicians to differentiate among these agents to select the most appropriate treatment for their patients with erectile dysfunction (ED). This randomized, double-blind, crossover head-to-head clinical trial compared patient preference, efficacy and safety of vardenafil and sildenafil in men with ED and diabetes, hypertension and/or hyperlipidemia. Prospective analysis was performed on two studies in which 1,057 men were randomized to vardenafil 20 mg ( N = 530) or sildenafil 100 mg (2 × 50 mg encapsulated tablets) ( N = 527) for 4 weeks. Following a 1-week washout, patients switched treatment for 4 weeks. Patients were asked about overall preference relating to their ED treatment, including "Overall, which medication do you prefer?" besides 11 other questions. Efficacy assessments after each treatment period included the erectile function (EF) domain score of the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) diary questions SEP2 and SEP3, Global Assessment Question (GAQ) and Treatment Satisfaction Scale (TSS). Data regarding adverse events were collected throughout the study. A total of 931 men (mean age 57.9 years) were included in the intent-to-treat (ITT) population. Non-inferiority of vardenafil over sildenafil was achieved for overall preference (vardenafil 38.9%, sildenafil 34.5% and no preference 26.6%). Additionally, the change from baseline in the EF domain score of the IIEF achieved nominal significance for vardenafil over sildenafil (10.00 vs. 9.40; P = 0.0052). Patients also had a higher percentage of positive responses for vardenafil for SEP2, SEP3, GAQ and 12 of 19 questions on the TSS. Both drugs were well tolerated. This randomized, double-blind, head-to-head trial in ED patients with cardiovascular risk factors demonstrated non-inferiority of vardenafil for overall preference. Vardenafil achieved nominal statistical superiority over sildenafil for several frequently used efficacy measures. Both drugs were well tolerated.
Rubio-Aurioles E, Porst H, Eardley I, Goldstein I. J Sex Med. 2006 Nov;3(6):1037-49.
Sildenafil, vardenafil and taladafil act by selectively inhibiting phosphodiesterase 5 (PDE-5) . They have no effect in the absence of sexual activity. The recommended dose of sildenafil is 50-100 mg (for men >65 years - 25 mg) 1 h before intercourse. The normal starting dose for vardenafil is 10 mg (roughly equivalent to 50 mg of sildenafil). Vardenafil should be taken 25-60 min prior to sexual activity, with a maximum dose frequency of once per day. Taladafil is the third impotence pill after sildenafil and vardenafil. Taladafil's longer half-life (17.5 h) as compared with sildenafil and vardenafil (4-5 h) results in a longer duration of action. Due to its 36-h effect, it is also known as the weekend pill . The recommended starting dose is 10 mg, taken prior to anticipated sexual activity.