Sexual Dysfunction in Patients with Hypertension: Implications for Therapy

Carlos M. Ferrario, MD, Pavel Levy, MD

In This Article

Effects of AIIAs on Sexual Dysfunction in Hypertensive Patients

Therapy with AIIAs and ACE inhibitors is generally not associated with development of sexual dysfunction in patients with hypertension ( Table II and Table III ),[6,12,31,39] although two questionnaire-based studies have reported a relatively high occurrence of sexual problems in patients receiving ACE inhibitors.[11,22] As noted by Rosen, "...hypertension therapy directed at the renin-angiotensin system was more likely to be associated with improvements in sexual distress scores than other forms of treatment, and less likely to lead to a deterioration in sexual function."[6] This statement is corroborated by two studies comparing blockers with either an ACE inhibitor or an AIIA.[12,39] In both of these studies, the blocker caused chronic worsening in sexual activity, whereas both the ACE inhibitor and AIIA had no long-term effect -- in fact, the AIIA improved sexual activity. For example, in a double-blind, crossover study by Fogari and colleagues,[12] 160 hypertensive patients with newly diagnosed hypertension were randomized to receive valsartan 80 mg once daily or carvedilol 50 mg once daily for 16 weeks. Sexual activity was assessed with a self-administered questionnaire containing a series of questions addressing the patients' interest in sex, difficulties getting or maintaining erections, and the number of times patients had sexual intercourse over a 2-week period. Despite similar effects on blood pressure by the two agents, AIIA therapy increased sexual activity (8.3 episodes/month of sexual intercourse at baseline to 10.2 at week 16), whereas blocker therapy significantly decreased sexual activity compared with baseline (8.2 to 3.7 episodes per month; p<0.01) and compared with AIIA (p<0.01).[12] Erectile dysfunction was a complaint of 15 patients receiving carvedilol (13.5%) and one patient receiving valsartan. These findings serve to illustrate the marked differences in the effects of blockers and AIIAs on sexual function (despite similar efficacy in reducing blood pressure) and suggest that AIIAs may offer therapeutic advantages with respect to quality of life.

More recent evidence supporting a beneficial effect of AIIAs in positively influencing several indices of sexual function, including erectile function, sexual satisfaction, and frequency of sexual activity, as well as perceived quality of life, is provided by a recent open-label study by Llisterri and colleagues[11] in hypertensive patients aged 30-65 years. This study evaluated the effect of the AIIA losartan in hypertensive subjects either with (n=82) or without (n=82) a diagnosis of sexual dysfunction, all of whom were selected consecutively from primary care clinics. Sexual dysfunction was diagnosed by means of a well accepted, self-administered questionnaire revalidated in an independent study of 60 additional hypertensive subjects. Of the 323 hypertensive male and female subjects in the initial sample, 82 men with sexual dysfunction (prevalence of 42.3%; 95% confidence interval, 35.3-49.3; age range, 30-65 years) received a 12-week regimen of losartan 50 mg/day. AIIA treatment for 12 weeks produced marked and statistically significant increases in sexual satisfaction, from 7.3% of patients at baseline to 58.5% of patients after AIIA therapy (p<0.001). In addition, this medication increased the proportion of patients with a high frequency of sexual activity (40.5% vs. 62.3%), improved the quality of life in 73% of patients, and decreased the percentage of patients reporting erectile dysfunction (75.3% vs. 11.8%). Overall, only 11.8% of the treated subjects did not report an improvement in sexual function with losartan. In the control group of hypertensive patients without sexual dysfunction, the AIIA produced comparable reductions in arterial blood pressure but no significant changes in erectile dysfunction, sexual satisfaction, frequency of sexual activity, or perceived quality of life (p>0.05). Changes in sexual dysfunction variables were unrelated to age, duration of hypertension, level of education, marital status, or blood pressure levels, or type of antihypertensive agent subjects received prior to study entry.

The potentially beneficial effect of AIIAs on sexual function in hypertensive patients is consistent with their excellent tolerability and adverse event profile observed in both short-term and long-term trials in hypertensive patients.[40,41] AIIAs are well tolerated in hypertensive patients, as evidenced by the similarity in the percentage of patients with clinical adverse experiences in AIIA-treated and placebo-treated patients.[40] This may have important clinical ramifications with respect to patients staying on therapy, an assertion borne out by a recent study showing that the percentage of patients continuing initial therapy with AIIAs was greater than that for ACE inhibitors, CCBs, blockers, or diuretics.[42]

Collectively, these studies suggest that AIIAs, such as losartan, may offer a therapeutic option to prevent and/or correct erectile dysfunction in patients with hypertension. The favorable effects of AIIAs on sexual function may be related, in part, to their ability to block ANG II, which has recently been proposed as a potential mediator of erectile function.[42] In addition, AIIAs may also cross the blood-brain barrier and have a direct positive effect on the central nervous system, an assertion supported by the recent finding that losartan, but not hydrochlorothiazide, improves cognitive function in elderly hypertensive patients.[43]