Effects of oral phentolamine, taken before sleep, on nocturnal erectile activity: a double-blind, placebo-controlled, crossover study DG Hatzichristou 1 *, A Apostolidis 1 , V Tzortzis 1 , K Hatzimouratidis 1 and D Kouvelas 1 1 Department of Urology and Center for Sexual Dysfunction, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece The objective of this study was to determine the effects of oral phentolamine, administered before sleep, on nocturnal penile erectile activity of men with mild to moderate erectile dysfunction (ED). We studied five patients with mild to moderate ED (mean age 34.8  8.13 and mean duration of ED 31.8  23.5 months), in a double-blind, placebo-controlled, crossover study. All patients received oral phentolamine (Vasomax TM ) at a dose of 40 mg and placebo for three consecutive nights respectively and were submitted to nocturnal penile tumescence and rigidity monitoring (NPTR) with the Rigiscan 1 device. NPTR parameters of the two 3-night recordings were evaluated and compared. Administration of oral phentolamine before sleep was associated with a statistically significant increase in the number of erectile events with rigidity  60% lasting  10 min (P ¼ 0.02), as well as the rigidity activity units (RAU) value per hour sleep, both at the base (P ¼ 0.023) and the tip of the penis (P ¼ 0.019). The number of events as measured by Rigiscan software (20% change in circumference), as well as tumescence activity units (TAU)=h values did not show any statistical difference. No adverse effects were recorded. It is concluded that oral phentolamine administered before sleep enhanced NPTR parameters associated with the quality of the erectile events. Such results provide a pathway for the development of a prevention strategy for ED. Future studies will elucidate whether vasoactive agents taken on a regular basis before sleep, can prevent ED in men at risk, protecting also minimally and moderately impotent patients to become moderately and severely impotent respectively. International Journal of Impotence Research (2001) 13, 303–308. Keywords: erectile dysfunction; nocturnal erections; prevention; phentolamine Introduction Recent epidemiological data determined that the annual incidence rate of erectile dysfunction (ED) is 26=1000 men=year and about one million new cases are expected annually in the USA alone. 1 Such high incidence rate, together with the advances in the treatment of ED — mainly due to the availability of oral agents in the market — brought into considera- tion the urgent need for the development of prevention strategies. An increasing body of evidence suggests that pharmacologic erections may prevent erectile dys- function (ED). 2,3 In their pioneer study, Montorsi et al demonstrated the beneficial effect of post- operative intracavernous injections of alprostadil on the recovery of spontaneous erections after nerve- sparing radical retropubic prostatectomy. 4 Such data gave us the idea to consider the administration of oral agents for ED prevention. Nocturnal erections have been proposed to play a protective role on the trabecular tissue, increasing tissue oxygenation, specifically during long periods of sexual abstinence. 5 As orally taken vasoactive drugs, such as sildenafil and phentolamine have shown to be effective in enhancing erectile capabil- ities, 6,7 it was postulated that it may be possible to pharmacologically manipulate nocturnal erections with regular administration of such agents before sleep. If such a hypothesis proves to be correct, an increase in the nocturnal erectile activity may have a beneficial effect on the overall erectile function, preventing ED in men at risk, as well as restraining further hypoxia-induced tissue damage in men with minimal or moderate corporal pathology. The present study represents the first step in the exploration of the above hypothesis. The objective of the study is to determine the effects of oral phentolamine, administered before sleep in men with mild to moderate erectile dysfunction, on nocturnal penile erectile activity. *Correspondence: DG Hatzichristou, 77 Mitropoleos str., 54 622 Thessaloniki, Greece. E-mail: hatzichr@med.auth.gr Received 3 January 2001; accepted 12 February 2001 International Journal of Impotence Research (2001) 13, 303–308 ß 2001 Nature Publishing Group All rights reserved 0955-9930/01 $15.00 www.nature.com/ijir