Sexual dysfunction is a common and very distressing symptom that affects up to 70 percent of men and women with MS. It is now discussed more openly and constructively than in the past. Some evidence to support a counselling intervention has been provided recently. There has also been an increase in the understanding of the mechanisms responsible for the symptoms and advances in treatment, although mainly in erectile dysfunction in men. Apart from specific neurological damage, the development of disability may have a major effect on the self-image of patients, which may in turn affect both their relationships and sexual function.

Management of Sexual Dysfunction in Women
The most frequently described symptoms include decreased sexual desire, diminished orgasm, difficulties with vaginal lubrication, and fatigue that interferes with sexual activity. Decreased vaginal lubrication can be treated with water-soluble lubricants, and dysesthesias may be relieved with carbamazepine or phenytoin. However, nitrergic nerves are also present in the corpus cavernosum of the clitoris and vaginal wall, so there is good rationale for expecting sildenafil (Viagra®) to have a beneficial effect. A randomized control trial is currently under way.

Management of Sexual Dysfunction in Men
Erectile difficulties are present in between 60 and 80 percent of men with MS, with symptoms ranging from difficulty sustaining an erection for intercourse, with normal nocturnal erections, to total failure of erectile function and difficulty with ejaculation in more severe disease. Clinical and neurophysiologic evidence strongly suggests a spinal origin of these symptoms. Up to 96 percent of patients have pyramidal tract signs, while physiological abnormalities implicating spinal involvement are seen in 85 percent of patients.

The value of discussing and providing relevant information cannot be underestimated.

Oral Treatments for Sexual Dysfunction
Recent advances in drug treatment, notably sildenafil (Viagra®), which has superseded all previously available therapy, are likely to have a major effect on the impact of this symptom. Release of nitric oxide from nerves supplying the arterioles of the corpora cavernosa increases intracellular levels of cyclic GMP, which results in smooth muscle relaxation and penile erection. The effect of cGMP is terminated by the enzyme phosphodiesterase, and sildenafil is an orally active inhibitor of this enzyme. A double-blind, randomized, placebo-controlled trial of 217 men with clinically definite MS with disability ranging between 2.0 and 6.0 on the EDSS has been carried out. The 16-week study included a 4-week run-in period. Patients were randomized to either placebo or 50 mg sildenafil to be taken 1 hour before intercourse at a maximum of once per day. The dose could be altered to either 100 mg or 25 mg, depending on therapeutic response and tolerability. The primary outcome measure was the International Index of Erectile Function (IIEF). One hundred and two of the 104 patients (98 percent) in the active arm completed treatment compared with 88 of the 113 patients (77 percent) receiving placebo.

The ability to achieve and maintain erections was significantly improved in the treatment group compared with controls (p<0.0001), and in those patients with improved erections (sildenafil responders) 92 percent reported an improvement in the ability to have satisfactory sexual activity. Adverse events were predominantly mild in nature, with headache (23.1 percent active group versus 5.3 percent in the placebo arm) and flushing (13.5 percent versus 1.8 percent) being the most common. There were three serious adverse events in each arm, none of which were thought to relate to the treatment. No cardiac symptoms were experienced in the treatment arm, although one patient in the placebo arm had a myocardial infarction during the study. A beneficial effect on related aspects of quality of life was also detected using the Life Satisfaction Checklist and the Erection Distress Scale. The treated group showed significant benefit in five of the eight components of the checklist, including life as a whole (p<0.001) and sexual life (p<0.001), but also partnership relation (p<0.001), family life (p<0.003), and social contacts (p<0.03).

Studies of this agent in women with sexual dysfunction suggest that sildenafil may be beneficial in a proportion of patients, particularly when lubrication is an issue.

More recently other agents with a similar mode of action but which may be more potent have become available, notably vardenafil and tadalafil. There is some evidence to suggest that vardenafil may be effective in patients who are unresponsive to sildenafil.

The only available agent that is claimed to improve ejaculatory function is yohimbine, which is thought to be an alphasympathetic agonist, but it has never been subjected to rigorous evaluation.

Other Approaches to the Treatment of Sexual Dysfunction

Intracorporeal pharmacotherapy has been in existence for almost two decades, initially with papaverine but more recently with prostaglandin E1 (alprostadil) at a dose of 20 μg. The latter is rapidly metabolized so that priapism and local fibrosis are very rare. Studies have shown it to be highly efficacious, with few, if any, systemic side effects. However, the disadvantages of having to inject are obvious, and patients frequently report penile pain with this treatment. There is also the option to use a medicated urethral system for erection that delivers a pellet of alprostadil into the urethra via a small applicator.

A mixture of nitric oxide–releasing dilatory creams has been evaluated in a placebo-controlled, cross-over study and was beneficial in 58 percent of men, while only 8 percent responded to the placebo. Vacuum pumps are occasionally used but have never been evaluated, and prosthetic surgery is not recommended in patients with MS.

In the view of the Committee, sexual dysfunction in men, particularly difficulty maintaining an erection, is now treated relatively easily. However, sexual dysfunction in women remains difficult to manage.