sildenafil-citrate and Multiple-Sclerosis

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS). The most common clinical manifestations of MS are spasticity, pain, vesico-urethral disorders, cognitive impairments, chronic fatigue and sexual dysfunction. This review aims to explore the possible therapeutic options for managing sexual dysfunction in people with MS (PwMS).. A thorough search of the PubMed Medline database was performed. Records were limited to clinical studies published between 01/01/2010 up to 01/01/2022. The results were screened by the authors in pairs.. The search identified 36 records. After screening, 9 records met the inclusion-exclusion criteria and were assessed. The pharmacological approaches investigated the effectiveness of sildenafil, tadalafil and onabotulinumtoxinA. Of the interventional studies the non-pharmacological investigated, the effectiveness of aquatic exercises, the application of pelvic floor exercises,the combination of pelvic floor exercises and mindfulness technique, the combination of pelvic floor exercises and electro muscular stimulation with electromyograph biofeedback, the application of yoga techniques and the efficacy of assistive devices like the clitoral vacuum suction device and the vibration device.. The management of sexual dysfunction in PwMS needs to be further investigated. A team of healthcare professionals should be involved in the management of SD in order to address not only the primary (MS-related) SD symptoms but the secondary and tertiary as well. The main limitations that were identified in the existing literature were related to MS disease features, sample characteristics and evaluation tools and batteries.

Topics: Exercise Therapy; Humans; Multiple Sclerosis; Pain; Sexual Dysfunction, Physiological; Sildenafil Citrate

Erectile dysfunction (ED) is reported in a high percentage of patients with central neurological disorders (CND)..   An up-to-date review on oral phosphodiesterase 5 inhibitors (PDE5): sildenafil, tadalafil, and vardenafil for individuals with CND and ED.. Various questionnaires on ED, such as the International Index of Erectile Function composed of 15 questions.. Internationally published clinical studies evaluating the efficacy and safety of PDE5 on subjects with CND and ED were selected.. Overall, 28 articles on PDE5 used to treat patients with CND and ED were included. With each of the three PDE5 compared to placebo or erectile baseline, literature reported significant statistical improvement (P < 0.01; P < 0.05) only in patients with spinal cord injury (SCI). PDE5 efficacy was documented for SCI patients up to 10 years. The most frequent predicable factor for PDE5 success was the presence of upper motoneuron lesion. Each of the three clinical sildenafil studies documented statistically significant improvement on erectile function in Parkinson's patients (P < 0.01; P < 0.05). Two studies reported discordant results about sildenafil's effectiveness on multiple sclerosis (MS) patients; one on tadalafil showed significant statistical efficacy on erection versus baseline (P < 0.01; P < 0.05). The only spina bifida article determined that sildenafil remarkably improved erectile function. Overall, drawbacks were mostly slight-moderate, except in subjects with multiple system atrophy where sildenafil caused severe hypotension.. PDE5 represent first line ED therapy only for SCI patients, though treatment results through meta-analysis were not possible. Encouraging results are reported for Parkinson's and MS patients. PDE5 use for other CND patients is limited for various reasons, such as ED and concomitant libido impairment caused by depression and/or sexual endocrinology dysfunctions, and because PDE5 may cause a worsening of neurological illness. Medical centers staffed by health professionals able to counsel patients on the possible use of PDE5 are needed.

Topics: Carbolines; Central Nervous System Diseases; Clinical Trials as Topic; Humans; Imidazoles; Impotence, Vasculogenic; Male; Multiple Sclerosis; Parkinson Disease; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Spinal Dysraphism; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Erectile dysfunction (ED) is a common sexual disease in male patients with multiple sclerosis (MS). Sildenafil citrate is considered as an effective drug in the treatment of male ED in the general population, but it has not been systematically reviewed in patients with MS.. To assess the efficacy and safety of sildenafil citrate for ED in patients with MS.. We searched the Cochrane (November 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4 of 4, 2011), MEDLINE (PubMed) (January 1966 to November 2011), EMBASE (January 1974 to November 2011) and the China Biological Medicine Database (CBM) (1979 to November 2011). We searched trials registers and conference proceedings and contacted pharmaceutical company and authors of included studies for additional data. There were no language restrictions.. Randomised controlled trials comparing sildenafil citrate with placebo or no treatment for ED in patients with MS.. Two review authors independently selected articles for inclusion, extracted data and assessed trial quality. Disagreements were resolved by discussion between review authors. Authors of included studies were contacted for additional information. Results were presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI).. Two randomised controlled trials involving a total of 420 patients were identified. Both trials investigated the short-term efficacy and safety of sildenafil citrate for ED in patients with MS. Patients taking sildenafil citrate were more likely to improve their ability to achieve and maintain an erection measured by International Index of Erectile Function and achieve vaginal penetration ( (RR 1.28, 95%CI 0.92 to 1.78) and complete intercourse measured by Sexual Encounter Profile diary (RR RR 1.38, 95%CI 1.00 to 1.90). and receive A global well respond measured by Global Assessment Question (RR 2.72, 95%CI 1.40 to 5.28) was reported. One trial showed sildenafil citrate is effective in quality of life improvement, while the other trial did not find any significant difference between both groups. Both included trials were judged as high risk of attrition bias. Adverse events were also reported: the most common were headache, flushing, rhinitis, visual disturbances and dyspepsia. Two patients suffered serious adverse events: one with coronary artery disease requiring triple bypass surgery and one with a cerebrovascular accident.. There is limited evidence to support sildenafil citrate as an effective treatment for ED in patients with MS. Future well designed randomised, double blinded, placebo-controlled trials with long-term duration are needed.

Topics: Erectile Dysfunction; Humans; Male; Multiple Sclerosis; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfones; Vasodilator Agents

Interferon (IFN) therapy is nowadays widely used in clinical practice. In the literature, there are very few reports of the association between IFN therapy and pulmonary arterial hypertension (PAH), and current guidelines do not mention IFNs as a risk factor for PAH. We describe a patient with multiple sclerosis who developed severe PAH after treatment with IFN-β-1a and the clinical response to sildenafil. Furthermore, we stress the need to further investigate the link between IFNs and PAH.

Topics: Adjuvants, Immunologic; Antihypertensive Agents; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Interferon beta-1a; Interferon-beta; Middle Aged; Multiple Sclerosis; Piperazines; Purines; Sildenafil Citrate; Sulfones

Neurologic erectile dysfunction presents a diagnostic and treatment challenge to the internist and urologist. Multiple chronic disease modalities and traumatic etiologies exist. Education regarding these conditions and a detailed and thorough history and office work-up are the best resources for the clinician. Treatment can follow the model of proceeding from the least to most invasive procedure (process of care), taking into account patient and partner satisfaction. Because the psychology of grief and loss may enter into treatment of some neurologic conditions (e.g., erectile dysfunction after radical retropubic prostatectomy, spinal cord injury, or chronic diseases), a whole-patient approach encompassing psychotherapy is warranted.

Topics: Chronic Disease; Diabetic Neuropathies; Erectile Dysfunction; Humans; Intervertebral Disc Displacement; Male; Multiple Sclerosis; Parkinson Disease; Penile Prosthesis; Phosphodiesterase Inhibitors; Piperazines; Prostatectomy; Purines; Sildenafil Citrate; Spinal Cord Injuries; Sulfones

We evaluated the safety and efficacy of sildenafil citrate for treating erectile dysfunction in patients with multiple sclerosis.. A total of 203 patients with multiple sclerosis (age range 18 to 50 years old) with erectile dysfunction were randomly assigned to receive 50 to 100 mg sildenafil (102 patients in group 1) or a similar regimen of placebo (101 patients in group 2) 45 minutes to 2 hours before sexual stimulation. Patients were asked to use at least 24 doses/attempts at home. Primary outcome measures consisted of responses to questions 3 and 4 from the International Index of Erectile Function questionnaires well as responses to Sexual Encounter Profile diary questions 2 and 3. We also assessed the number of attempts at sexual intercourse, the number of attempts that were successful and adverse drug effects.. Improved erections (positive response to the Global Assessment Questionnaire) were reported by 32.8% of patients receiving sildenafil and 17.6% of those receiving placebo (p = 0.04). For Sexual Encounter Profile question 2 (successful penetration) the increase from baseline in mean per patient percentage of yes responses was 29.4% after sildenafil vs 18.8% after placebo (p = 0.04). The proportion of successful sexual attempts ranged from 12% to 26% for sildenafil and from 9% to 21% for placebo, respectively (p = 0.044). Of patients taking sildenafil and placebo 24 (23.5%) and 9 (8.9%) experienced 81 and 31 adverse events, respectively (p = 0.01).. Compared with placebo, sildenafil has little effect on multiple sclerosis emergent erectile dysfunction and, therefore, cannot be recommended for the routine treatment of erectile dysfunction in patients with multiple sclerosis. This finding implies that there must be other mechanisms that are not affected by sildenafil or are resistant to the effects of sildenafil.

Topics: Adult; Double-Blind Method; Erectile Dysfunction; Evoked Potentials, Somatosensory; Humans; Male; Middle Aged; Multiple Sclerosis; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Identifying and effectively treating erectile dysfunction (ED) can result in an improvement of the quality of life (QoL) in men with multiple sclerosis (MS).. This randomised, double blind (DB), placebo controlled, flexible dose study with an open label extension (OLE) assessed efficacy, QoL, and safety of sildenafil citrate in men with MS and ED. Overall, 217 men received sildenafil (25-100 mg; n = 104) or placebo (n = 113) for 12 weeks. Efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire that includes questions on achieving (Q3) and maintaining (Q4) an erection as well as a global efficacy question (GEQ). QoL was also assessed.. After 12 weeks, patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo (p<0.0001), and 89% (92/103) reported improved erections compared with 24% (27/112) of patients receiving placebo (p<0.0001). At the end of the OLE phase, 95% of men reported improved erections. Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections (97% v 26%). Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo (p<0.05). The total mean score for the QoL questionnaire improved by 43% for the sildenafil group versus 13% for the placebo group (p<0.0001). Treatment related AEs were predominantly mild in nature, and no patient discontinued due to an AE.. Sildenafil treatment for ED in men with MS was effective and well tolerated, and resulted in significant improvements in both general and disease specific QoL variables.

Topics: Adult; Aged; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Male; Middle Aged; Multiple Sclerosis; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Vasodilator Agents

We assessed the tolerability, safety and efficacy of sildenafil for the treatment of women with sexual dysfunction secondary to multiple sclerosis, as well as the role of somatosensory evoked potential neurophysiological testing.. We performed a double-blind, randomized, placebo controlled, crossover study investigating the effects of sildenafil in women with multiple sclerosis and sexual dysfunction. Assessments were done by validated questionnaires. Pudendal and tibial evoked potentials were also recorded.. A total of 19 women completed the 2 arms of the double-blind phase and 12 completed the optional open label extension phase. Statistically significant improvement following sildenafil was only reported in the lubrication domain of sexual function during the double-blind phase. There was no overall change in quality of life after sildenafil. There was a significant correlation between the latency of tibial and pudendal evoked potentials.. Sildenafil only appeared to produce limited benefit in certain individuals with female sexual dysfunction. Some measure of the extent of neurological deficit in these patients could be ascertained from the latency of tibial evoked potentials, which correlated with pudendal evoked potentials. However, it could not predict the extent of sexual dysfunction. Sildenafil is unlikely to help all patients with neurogenic female sexual dysfunction.

Topics: Algorithms; Cross-Over Studies; Double-Blind Method; Female; Humans; Multiple Sclerosis; Phosphodiesterase Inhibitors; Piperazines; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones; Surveys and Questionnaires

Topics: Animals; Arthritis; Cyclic Nucleotide Phosphodiesterases, Type 4; Encephalomyelitis, Autoimmune, Experimental; Freund's Adjuvant; Indium; Indoles; Molecular Structure; Multiple Sclerosis; Oligodendrocyte-Myelin Glycoprotein; Phosphodiesterase 4 Inhibitors; Quinoxalines; Rats; Structure-Activity Relationship; Zebrafish; Zebrafish Proteins

While it has recently been shown that sildenafil (Viagra®) has a protective effect on myelination/remyelination, the mechanism of this protection is still unknown. In general, cytokines, chemokines and metalloproteinases have a pro-inflammatory action, but can also exert a role in modulating glial cell activation, contributing to the balance of cell response. Investigating these molecules can contribute to clarifying the mechanisms of sildenafil neuroprotection. In addition, it is not known whether sildenafil is able to restore an already installed neurodegenerative process or if the treatment period is critical for its action. The aim of the present study was to evaluate, in a cuprizone (CPZ)-induced demyelination model, the effects and mechanisms of time-dependent treatment with sildenafil (beginning 15 days after neurodegeneration and continuing for 15 days, or starting concomitantly with neurodegeneration and continuing for 30 days) on neuroinflammation and remyelination. Neuroinflammation and demyelination induced by CPZ in rodents has been widely used as a model of multiple sclerosis (MS). In the present study, five male C57BL/6 mice aged 7-10 weeks were used per group. For four weeks, the groups received either cuprizone (CPZ) 0.2% mixed in feed or CPZ combined with the administration of sildenafil (Viagra®, Pfizer, 25 mg/kg) orally in drinking water, starting concurrently with (sild-T0) or 15 days (sild-T15) after the start of CPZ treatment. Control animals received pure food and water. The cerebella were dissected and processed for immunohistochemistry, immunofluorescence (frozen), Western blotting, Luxol fast blue staining and transmission electron microscopy. Magnetic resonance was performed for live animals, after the same treatment, using CPZ 0.3%. CPZ induced an increase in the expression of IL-1β and a decrease in MCP-1, CCR-2, MBP and GST-pi, as well as promoting damage in the structure and ultra-structure of the myelin sheath. Interestingly, the administering of sild-T0 promoted a further increase of MMP-9, MCP-1, and CCR-2, possibly contributing to changes in the microglia phenotype, which becomes more phagocytic, cleaning myelin debris. It was also observed that, after sild-T0 treatment, the expression of GST-pi and MBP increased and the myelin structure was improved. However, sild-T15 was not efficient in all aspects, probably due to the short treatment period and to starting after the installation of the degenerative process. Therefor

Topics: Animals; Chemokine CCL2; Cuprizone; Demyelinating Diseases; Matrix Metalloproteinase 9; Mice; Multiple Sclerosis; Myelin Sheath; Phosphodiesterase 5 Inhibitors; Receptors, CCR2; Signal Transduction; Sildenafil Citrate

Topics: Animals; Azoles; Bipolar Disorder; Carbazoles; Clinical Trials, Phase II as Topic; Dipyridamole; Drug Approval; Drug Evaluation, Preclinical; Drug Industry; Drug Repositioning; Drugs, Generic; Dry Eye Syndromes; Epilepsy; Humans; Isoindoles; Mice; Multiple Sclerosis; Neoplasms; Off-Label Use; Organoselenium Compounds; Patents as Topic; Sildenafil Citrate; Zidovudine

Sildenafil induces cGMP accumulation through phosphodiesterase-5 (PDE5) inhibition. cGMP-pathways protect oligodendrocytes and modulate astroglial and microglial reactions. Microglia and astrocytes play an important role in perpetuating multiple sclerosis (MS), a chronic inflammatory disease characterized by demyelination. Therefore, sildenafil can be a potential tool for MS treatment. The present study investigated the effects of sildenafil on the myelin structure and astrocyte/microglia-mediated neuroinflammation in an animal model of MS. Cuprizone-induced demyelination and neuroinflammation in rodents has been widely used as a model for MS. Herein, five male C57BL/6 mice (7-10 weeks old) were used per group. Over a 4-week period, the different groups received the following: (1) cuprizone (0.2%) mixed into the chow; (2) cuprizone in the chow and sildenafil (Viagra®; 3, 25 or 50mg/kg) in the drinking water; or (3) pure chow and water (control group). Cerebella were analyzed using transmission electron microscopy, western blotting, immunohistochemistry and luxol fast blue staining. Cuprizone induced tissue damage, with an increase in GFAP, Iba-1 and COX-2 and demyelination in comparison to the control group. However, cuprizone did not affect the expression of cytokines (TNF-α, IFN-γ, IL-1β and IL-2). Sildenafil reduced GFAP (25 and 50mg/kg) and Iba-1 expression (25mg/kg) in comparison to the cuprizone group, indicating the modulation of astrocytes and microglia, respectively. Sildenafil preserved myelin and axons ultrastructure and strongly reduced IFN-γ, TNF-α, IL-1β, IL-2 and COX-2 expression in comparison to the control and/or cuprizone groups. The results demonstrate a protective effect of sildenafil in the cerebellum. Thus, well-designed clinical trials may demonstrate that the oral administration of sildenafil can be suitable for individuals with MS and other neuroinflammatory/neurodegenerative diseases, providing additional benefits to current treatments.

Topics: Animals; Cerebellum; Cuprizone; Cyclooxygenase 2; Cytokines; Demyelinating Diseases; Disease Models, Animal; Down-Regulation; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Immunoblotting; Male; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Acute Disease; Adult; Cardiac Output, Low; Catheterization; Critical Care; Electrocardiography; Female; Femoral Artery; Gastrectomy; Humans; Multiple Sclerosis; Peptic Ulcer Perforation; Piperazines; Pulmonary Embolism; Purines; Sildenafil Citrate; Sulfones; Thrombolytic Therapy; Vasodilator Agents; Vena Cava Filters

A 23-year-old woman with multiple sclerosis developed respiratory symptoms 3 years after introduction of interferon beta-1b. The diagnosis of pulmonary arterial hypertension (PAH) was established. The patient partially responded to sildenafil and bosetan treatment. This is the first report of PAH, associated with interferon beta therapy. As shown in experimental models, interferon treatment can induce PAH by stimulation of thromboxane cascade and secretion of various inflammatory mediators.

Topics: Antihypertensive Agents; Bosentan; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Immunologic Factors; Interferon beta-1b; Interferon-beta; Multiple Sclerosis; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Young Adult

The aim of this study was to analyze the sexual dysfunction in patients affected by multiple sclerosis.. From January 2005 to December 2007, 221 consecutive patients, 97 women and 124 men, were included in the study. Age range was 20+/-65 years (average 38.77). Fifty-two patients, 14 women (26.9%) and 38 men (73%), among those who have had sexual dysfunctions, showed their will to tackle their problem, and were thus taken into consideration by the Department of Andrology. Sexual activity of these patients has been estimated by self-administered questionnaire, through the International Index of Erectile Function (IIEF) for men and Index of Female Sexual Arousal (IFSA) for women. All 64 patients started a domiciliary therapy with sildenafil 50 mg, and in case of failure, sildenafil 100 mg. Results have been estimated for men according to the IIEF questionnaire and to the answers to the third and fourth question, concerning the capacity to have and keep an adequate erection during a sexual intercourse, and for women according to the IFSA questionnaire and to the answers given to questions number 1, 5, 6, and 10.. Among the 124 male patients, 25 (20.1%) had a serious deficiency of the erectile function (score IIEF<10), 11 (8.8%) had a moderate deficiency (score from 11 to 16), and 20 (16.12%) had a light deficiency (score from 17 to 25). Twenty-five patients affected with serious erectile deficiency, also reported a contemporaneous decrease of libido. Among the 97 female patients, 22 (28.86%) of them reported a serious decrease of the genital sensitivity and of the sexual desire; 22 (22.68%) of them reported instead a serious decrease of the vaginal lubrication; 9 (9.2%) reported a moderate decrease of the sensitivity, and 10 (10.30%) reported a moderate decrease of the vaginal lubrication. According to Disability Scale Expanded Score 52 male patients showed a 2.6 mean score (range 1.5-7); 14 female patients showed a 2.9 mean score (range 3-6). The answers to IIEF questions number three and four, and to the IFSA questions number 1, 5, 6 and 10 reported the achievement and keeping of an adequate erection after a follow-up of 4 sexual intercourse, and lubrication and sensitivity during a sexual intercourse in all the cases analysed.. Sildenafil has been effective and safe in the treatment of sexual dysfunctions for both sexes. In all analysed patients sexual deficiency was due to the neurological and central nervous system on which depend different dysfunctions correlated with the extension and the gravity of the multiple sclerosis. IIEF questions number 13 and 14 and IFSA questions number 21 and 22 showed a clear improvement of the sexual life quality of these patients, after sildenafil therapy.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Phosphodiesterase Inhibitors; Piperazines; Purines; Sexual Dysfunction, Physiological; Sildenafil Citrate; Sulfones

Topics: Denmark; Drug Costs; Erectile Dysfunction; Humans; Insurance, Pharmaceutical Services; Male; Multiple Sclerosis; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Sweden; Vasodilator Agents