Clinical Briefs

By Louis Kuritzky, MD

Sildenafil Citrate for Erectile Dysfunction in Men Receiving Multiple Antihypertensive Agents

Erectile dysfunction (ED) is commonplace in men at middle-age and beyond, the same era when hypertension (HTN) incidence begins to rise steeply. Since ED is widely recognized as a vasculopathy, in large part related to endothelial dysfunction, HTN can contribute to the burden of ED. Additionally, antihypertensive medications can lead to ED.

Sildenafil can produce dramatic, potentially disastrous blood pressure reductions if concomitantly administered with organic nitrates (eg, nitroglycerin), and is thusly contra-indicated. Little studied is the efficacy and safety of sildenafil in men already on multiple antihypertensive agents.

Pickering and colleagues studied middle-aged men with ED (n = 562), all of whom were taking 2 or more antihypertensives. Men were randomized to sildenafil (titrated to most efficacious, best tolerated dose) or placebo, and monitored for medication efficacy as well as adverse events.

Sildenafil provided efficacy in restoring erectile function similar to that seen in prior trials including non-hypertensive patients. It was also well tolerated, and sildenafil-related hypotension was not identified. These data are encouraging that sildenafil may be used safely and efficaciously in men already receiving multi-drug regimens for HTN.

Pickering TG, et al. Am J Hypertens. 2004;17:1135-1142.

Risk of Fracture after Androgen Deprivation for Prostate Cancer

In the population of men with advanced prostate cancer (PCA) as a whole, androgen deprivation, through medical or surgical orchiectomy, produces benefits in morbidity and mortality. In 2 distinct PCA populations—men with localized disease, and men with post-prostatectomy PSA elevations—gonadotropin-releasing hormone agonists (GNRH) are finding increased use, despite lack of proof for survival advantage. Because androgen deprivation results in rapid bone loss, an increased risk of fracture would be anticipated to result. Data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and Medicare provided the information from which 50,613 men with prostate cancer could be studied.

Between 1992 and 1997, the relative risk of any fracture for men who had received nine or more doses of 9 was increased approximately 1.5 fold. The relative risk for fracture requiring hospitalization was even greater.

Indeed, men who received orchiectomy or greater than 9 doses of GNRH in the year after diagnosis had a lower fracture-free survival rate, compared with those who did not receive androgen deprivation. Noting these risks, Shahinian and colleagues suggest caution, at least in the distinct populations mentioned above, in use of androgen deprivation until benefits of treatment are more clearly delineated.

Shahinian VB, et al. N Engl J Med. 2005;352:154-164.

Chronic Stress Accelerates Ultraviolet-Induced Cutaneous Carcinogenesis

Long-term consequences of stress in human beings are difficult to measure, but it is believed that excessive emotional stress contributes to important adverse health outcomes such as myocardial infarction. Whether stress impacts cancer is little understood. To elucidate this issue, Parker and colleagues studied carcinogenesis in animals.

Mice were exposed to the stressor of being placed in a compartment (without opportunity for escape) for 60 minutes daily containing odor from fox urine, one of their natural predators. After 2 weeks of daily stress, the frequency was reduced to thrice weekly for 30 weeks. During the study period, animals were irradiated with UV light known to induce skin lesions.

Animals exposed to stress began to manifest neoplasm dramatically earlier than control animals (8 weeks vs 21 weeks), and with greater frequency (5 fold-increase in stress-subjected animals). Stressed animals in which tumors developed survived less well compared to controls (who also developed tumors).

Although animal studies do not directly translate into human agenda, these data support the conceptual framework for a deleterious impact of stress upon carcinogenesis, as well as survival from established carcinoma.

Parker J, et al. J Am Acad Dermatol. 2004;51:919-922.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.