1 Division of Thalassaemia and 2 Department of Microbiological Science and Gynaecological Science, Ospedale S.Bambino, Catania, 3 Research Group for Sexology, Section of Dept for Gynaecological Science, University of Catania, Ospedale S.Bambino, Catania and 4 Division of Urology, Ospedale Vittorio Emanuele, Catania, Italy
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Abstract |
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Key words: erectile dysfunction/fertility/haemochromatosis/iron load/thalassaemia
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Introduction |
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Current treatments for impotence vary according to the cause (Morley and Kaiser, 1993; Feldman et al., 1994
). A distinction needs to be made between intrapsychic or relational problems on the one hand, and organic problems on the other (Buvat et al., 1997
). When organic factors are present, mechanical, surgical or pharmacological solutions are adopted in order to restore erection (Morales, 1993
; Caruso et al., 1997
). In patients affected by vascular pathologies in the pelvic area, by diabetes mellitus or by neurological disordersside effects of prescribed drugsthe intracavernous injection (ICI) of prostaglandins has proved to be immediately effective (Ishii et al., 1989
). However, such treatment can be accompanied by pain, priapism, haematoma and fibrosis (Lakin et al., 1990
).
Recently, it has become possible to administer prostaglandins transurethrally. This constitutes a safe method (that is only relatively invasive) for pharmacological treatment of impotence, and offers an alternative to existing therapies. Although erectile disorders in thalassaemic patients are presumably to be attributed to endocrine factors, we did not take pathogenic criteria into consideration, choosing instead to assign priority to clinical symptoms. We thus decided to consider the possibility of restoring erection using the transurethral application of E1 prostaglandins (alprostadil). The aim of our research was to test the effectiveness of the drug, and the response of erection by the erection assessment scale (Ishii et al., 1989). The clinical assessments were based on the transurethral administration of prostaglandins in a clinical setting, with erection grade scored by the clinicians themselves. Since a more extensive assessment of the patients' sex life will be included in a future research programme, we did not evaluate any home use by self-administration.
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Case report |
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Investigations
Blood samples were taken from each patient for measurement of plasma concentrations of FSH, LH, prolactin, total testosterone and free testosterone, at 08:00, 13:00 and 18:00 hours. All plasma hormone concentrations were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits (Roche, Monza, Italy).
Doppler sonography of the cavernous arteries was carried out in basal and dynamic conditions, using an ICI of 1.5 or 2.5 µg of prostaglandin E1. The intracavernous test with prostaglandins on men affected by erectile dysfunction is usually carried out using 10 µg of PGE1; instead, each thalassaemic patient was tested with 1.5 µg or 2.5 µg by ICI. This dose of prostaglandin E1 was chosen for thalassaemic men who were patients with chronic hypoxia, and consequently might be at risk of priapism.
After the endocrine and instrumental findings had been considered, and after written informed consent had been received from each of the patients enrolled, a 500 µg dose of alprostadil was administered transurethrally (MUSE®; Vivus, Menlo Park, CA, USA). The alprostadil was introduced into the distal urethra using an appropriate system. Patients were asked to urinate immediately before the application, so that the residual urine would facilitate insertion of the applicator. After administration, a genital massage was performed along the ventral shaft of the penis, to improve absorption of the drug through the urethral wall.
The response was measured with the erection assessment scale (EAS) (Waldhauser and Schramek, 1988; Ishii et al., 1989
), and graded as follows: 1 = no response at all; 2 = slight tumescence; 3 = reasonable tumescence but without sufficient rigidity; 4 = enough erection for coitus; and 5 = complete rigidity.
The times from drug administration to response and duration of the response were recorded.
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Results |
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Intraurethral application of alprostadil produced a response of 34 on the EAS (Table II). The average minimum response time was 20 min, and average maximum response time was ~60 min. On average, erection subsided after ~3045 min. Patient A reported coitus and orgasm at home, as a distal, non-pharmacological effect. None of the patients reported priapism. Only patient A complained of discomfort during and after the prostaglandin application, in the form of slight pain and stinging in the urethra.
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Discussion |
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As far as the gonads are concerned, the testicular biopsies have revealed: (i) an anatomopathological situation of hypogonadotrophic hypogonadism with massive haemosiderosis, above all at the tubular level (Fink, 1964); (ii) interstitial fibrosis (Kuo et al., 1968
); and (iii) thickening and hyalinosis of the basal membrane of the seminiferous tubules (Cianciulli and Del Poeta, 1986
). These aspects could be the reason for the absence of response to testosterone treatment. As regards the anatomopathological factors in the erection process, there are very few in-vivo or autopsy data available in the literature. Since siderosis is systemic in haemochromatosis, whether primary or post-transfusion, one might also postulate an induced effect from iron load overlapping that of other organs or glands where its presence is well documented, namely the liver, heart, pancreas and gonads (De Sanctis et al., 1992
; Lombardo et al., 1995
). Hence we suggest that the iron deposit is associated first with interstitial siderosis of the interlacunar trabeculae of the corpora cavernosa, and subsequently with a situation of fibrotic replacement, involving a consequent reduction and/or loss of elasticity and therefore hindering erection.
Our study examined thalassaemic patients with a chronic erectile disorder for whom the therapy chosen was the transurethral application of prostaglandins. Usually, the therapy appears to be well tolerated, it is only relatively invasive, does not give rise to unpleasant side effects such as pain or haematoma, and definitely increases compliance (Padma-Nathan et al., 1997b). With regard to the use of ICI in thalassaemia, the absence of sufficiently well-documented data makes it difficult to assess whether there exists a greater risk of priapism than in patients with other pathologies. ICI is clearly not recommended in the case of sickle-cell anaemia, where the occurrence of priapism is one of the complications of this illness (Fowler et al., 1991
). For thalassaemic patients, even if the pathogenic situation is clearly different, it is considered more appropriate to adopt the transurethral method, in part due to a lack of documentation in this area. Moreover, in patients affected by erectile dysfunction on a vascular and/or psychogenic level, the dilating of the arteries attendant upon the application of alprostadil is seemingly more widespread than in patients treated with ICI. Thalassaemic patients could benefit from the dilation of the arteries accompanying the application of alprostadil, since it may compensate for the delay in erection which, as mentioned above, normally follows the administration of prostaglandins (Gesundheit et al., 1996
).
By way of conclusion, it may be said that this pilot study produced satisfactory results. As a consequence, thalassaemic patients may become more at ease with themselves and their illness, improve their quality of life, and achieve a successful, stable relationship with their partner. This restored self- confidence will naturally have a positive effect on the patients' behaviour in society, enabling them to enjoy fundamental emotional experiences such as falling in love, having children, and a rewarding sex life. Thalassaemic patients are thus given the opportunity to establish their place in the world and in the order of things, and to appease the basic human instincts of self-preservation and survival of the species. In this respect, it should be stressed that treatment with alprostadil does not alter the total amount of prostaglandins in the spermatozoa, and thus does not affect the patient's ability to have children. In vitro, alprostadil has no effect on the motility, progression and integrity of the spermatozoa (Hellstrom et al., 1996).
It is therefore the case that the transurethral application of alprostadil appears to restore erection. We thus believe that treatment with alprostadil can be an effective, non-invasive therapeutic approach for thalassaemic patients with erectile dysfunction.
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Acknowledgments |
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Notes |
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References |
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Submitted on November 18, 1999; accepted on July 21, 2000.