1 Introduction

Although there is no precise data on the occurrence of erectile dysfunction, it is estimated that around 10% of male population in Indonesia suffer from this sexual dysfunction. This condition is known to diminish the self-esteem, cause emotional disturbances, and interfere with normal sexual relationship.

Current treatment of erectile dysfunction consists of 3 options as follows: 1) First-line therapy includes psychosexual therapy, oral medication, and use of vacuum constriction device. 2) Second-line therapy consists of intracavernous injection of vasoactive agents and transurethral application of alprostadil. 3) Third-line therapy is penile implant (prostheses)^[1].

As an optional treatment, intracavernous injection of vasoactive agents has been used widely in many part of the world. However, the injection method becomes a restriction for many people because of its side effects like pain, priapism, and fibrosis. Therefore the development of a new method to apply the vasoactive agent is expected.

The transurethral method in application of vasoactive agent seems to be more comfortable with less side effects compared to intracavernous injection. In November 1996, United States FDA cleared a transurethral application of alprostadil with the brand name MUSE (Medicated Urethral System for Erection) for marketing at doses of 125 g, 250 g, 500 g, and 1000 g.

2 Materials and methods

2.1 Patients

Twenty patients aged between 32-74 years old were recruited in this study. They were patients who came to the clinic to seek some treatment for their erectile dysfunction problem. Their mean age was 51 years old.

1)   The patients recruited were required to meet the following inclusion criteria:
*  Adult males 18 years or older with a subjective complaint or erectile dysfunction.
*  They were to provide written informed consent.
*  They were to agree not to use other forms of treatment for erectile dysfunction during the course of observation.
*  Have screening of laboratory values done within the acceptable range including platelet count, chemistry panel (albumin, GOT, GPT, alkaline phosphatase, bilirubin, creatinine, total cholesterol, LDL, HDL, triglyceride, uric acid), PSA, testosterone, and urine analysis. The laboratory examination was performed during the screening evaluation and at the end of the study (except for testosterone, which was determined at recruitment only).

2)    Patients were  excluded from the the study if they had:
*  A known allergy or hypersensitivity to alprostadil.
*  A history of sickle-cell disease or trait, multiple myeloma, thrombocythemia, polycythemia, or any other medical condition that, in the judgment of the investigator, would contraindicate the administration of the study medication or interfere with the study evaluations.
*  A history of myocardial, uncontrolled congestive heart failure (dyspnea at rest or upon minimal exertion), or unstable angina (chest pain more than twice a week while on therapy) within the previous 6 months. 
*  Abnormal penile anatomy or poor personal hygiene that the investigator felt would have interfered with intraurethral administration.
*  A history of urethral stricture, balanitis, severe hypospadias or curvature, or acute or chronic urethritis.
*  A current urinary tract infection or known sexually transmitted disease.
*  A current or prior penile implant or indwelling (Foley type) urethral catheter.
*  A partner who is pregnant or attempting to become pregnant during this study.
*  Participated in an investigational drug evaluation within the past 30 days, or have previously been enrolled in this study.

3) Partners of the patients included in this study were required to:
*  Be at least 18 years of age.
*  Provide written informed consent.
*  Be willing to comply with all study requirements and visit schedules.
*  Desire treatment of their partner's erectile dysfunction.
*  Be willing to use adequate contraception while participating in the study (if of childbearing   potential).

4) Partners of the patients were excluded if they had:
*  a known allergy or hypersensitivity to alprostadil.
*  any significant medical conditions that, in the opinion of the investiga
tor, would preclude study participation.
*  dyspareunia.
*  conceived or were attempting to become pregnant during the study.

2.2 Methods     

This study was an open-labelled treatment study consisting of two parts.

Part 1: Eligible patients were titrated in the clinic until they identified a dose that produced an erection sufficient for intercourse (scale 4 or 5). The in-clinic-titration started with a dose of 250 g and proceeded in a stepwise manner to 500 g and 1000 g on separate clinic visits at the interval of 2-3 days. Each in-clinic titration dose was evaluated at 15-min intervals over a one hour period for erection assessment, blood pressure and pulse. The erection assessment scale was as follows: 1=no response, 2=some enlargement, 3=full enlargement but not sufficient for intercourse, 4=erection sufficient for intercourse, 5=rigid erection.

3 Results

3.1 Etiology

The etiology of the erectile dysfunction was as follows:

4 Discussion

The era of the second-line therapy  actually started in 1982 when Virag introduced papaverine that produced penile erection when injected intracavernously^[2,3].

However, the repeated use of papaverine could cause pathological changes, like fibrosis, edema, degeneration, and atrophy of the corpus cavernosum smooth muscle^[4].

Although the side effects of  intracavernous injection for alprostadil are not as serious as those of papaverine^[5-10], the need for intracavernous injection is still a restriction for many patients. Therefore  the development of a transurethral method for alprostadil application seemed  to offer a more comfortable and safer approach than injection.

Based on the present study, after transurethral application of alprostadil, 75% of  patients achieved erection scale 4 or 5 with successful intercourse. The remaining 25% only achieved scale 2 or 3 that was not sufficient for intercourse.  However, from the patients achieving scale 4 or 5, only 60 % continued to be involved in the study, while 40% withdrew from the study because of pain, either during application, during erection, or during intercourse.

This data is similar with that presented by Padma-Nathan^[11] and Williams et al^[12]. They had observed 64%-65.9% of the patients involved in their study achieved maximal penile response of scale 4-5 sufficient for intercourse.

Williams et al^[12] showed that the in-home use of alprostadil gave a better result in producing an erection. They reported that 69% of the patients using transurethral alprostadil at home had  sexual intercourse compared to 64% of the patients in the clinic. We also indicated a better result at home for certain patients. This difference in reaction may be caused by psychological factors. The environmental situation at home being more comfortable  for them, and the surroundings may not pose extra stress on  some of the patients.

Penile pain is a common side effect of transurethral application of alprostadil as also reported by Padma-Nathan (35.7% of the patients during clinical testing and 32.7% during home treatment)^[11]. This side effect was the only reason  for withdrawal  of some patients from the study.

Acknowledgements

References

[1] Rosen R, Goldstein I, Padma-Nathan H. A process of care model. Evaluation and  treatment of erectile dysfunction. The University of Medicine and Dentistry of New Jersey-Robert Wood Johnoson Medical School. 1998; p 16-8.
[2] Virag R. Intracavernous injection of papaverine for erectile failure. Lancet 1982; 2: 938.
[3] Virag R, Frydman D, Legman M. Intracavernous injection of papaverine as diagnostic and therapeutic method in erectile failure. Angiology 1984; 35: 79- 87.
[4] Adaikan PG, Ng SC, Chan C, Kumar J, Lau LJ, Ratnam SS. Intracavernous injection therapy: long term effect-animal studies/human results. Int J Impotence Res 1994;  6 Suppl 1.
[5] Adimoelja A. Prostaglandin-E₁ intracorporal injections in selective and half-way erectile dysfunction. In: Proceedings of the 4th Biennial Asia Pasific Meeting on Impotence. Denpasar, Indonesia. November 18-20, 1993; p 94-6.
[6] Pangkahila W. Intracavernosal injection of PGE₁ for the treatment of impotence. Presented in the World Congress of Human  Reproduction. Denpasar, Indonesia. April 4-9, 1993.
[7] Pangkahila W. Intracavernosal injection of prostaglandin E₁ in non-organic impotence. Presented in the 6th National Congress of Andrology and 3rd International Symposium on New Perspective of Andrology in Human Reproduction. Manado, Indonesia. September 19-24, 1994.
[8] Stackl W, Hasun R, Marberger M. Intracavernous injection of PGE₁ in impotent men. J Urol 1988; 40: 66-8.
[9] Tulloch AGS, Keogh EJ, Early CM, Cherry DJ, Lord DJ. The  management of impotence. Presented at the National Congress of Endocrinology. Jakarta. 1985.
[10] Waldhauser M, Schramek P. Efficiency and side effects of prostaglandin-E₁ in the  treatment of erectile dysfunction. J Urol 1988; 140: 525-7.
[11] Padma-Nathan H, Hellstrom WJG, Kaiser FE, Labasky RF, Lue TF, et al. Treatment of men with erectile dysfunction with transurethral alprostadil. N Engl J Med 1997; 336: 1-7.
[12] Williams G, Abbou C-C, Amar ET, Desvaux P, Flam TA, Gesundheit N, et al. International study of the effect of transurethral alprostadil on erectile function and quality of life. Presented in 6th Biennial APSIR Meeting on Impotence. Kualalumpur, Malaysia. October 22-26, 1997.