Current issues of ACP Journal Club are published in Annals of Internal Medicine


Sexual dysfunction in men was greater with chlorthalidone than with placebo, acebutolol, amlodipine, doxazosin, or enalapril

ACP J Club. 1997 Jul-Aug;127:6. doi:10.7326/ACPJC-1997-127-1-006

Source Citation

Grimm RH, Grandits GA, Prineas RJ, et al., for the TOMHS Research Group. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS). Hypertension. 1997 Jan;29:8-14.



To compare the effects of 5 antihypertensive drugs on sexual function in patients with stage I diastolic hypertension.


Randomized, double-blind, placebo-controlled trial with 4-year follow-up (Treatment of Mild Hypertension [TOMHS]).


{4 clinical research units in the United States.}*


902 patients 45 to 69 years of age (mean age 55 y, 62% men) who had stage I diastolic hypertension and no cardiovascular disease. 39% of patients were not taking antihypertensive medication at baseline (mean diastolic pressure 90 to 99 mm Hg), and 61% were taking antihypertensive medication (mean diastolic pressure 85 to 99 mm Hg). Exclusion criteria were body weight ≥ 50% above or ≥ 10% below desirable weight, excess alcohol intake, excess restaurant meals, or unwillingness to comply with a lifestyle-modification program. Follow-up was > 90%.


Patients were allocated to placebo (n = 235) or 1 of 5 antihypertensive agents: acebutolol, 400 mg/d (n = 132); amlopidine, 5 mg/d (n = 131); chlorthalidone, 15 mg/d (n = 136); doxazosin, 2 mg/d (n = 134); or enalapril, 5 mg/d (n = 135). If blood pressure remained elevated, a step-up protocol was invoked.

Main outcome measures

Sexual function at 24 and 48 months was compared with baseline assessment, each drug group was compared with the placebo group, and the 5 drug groups were compared with each other.

Main results

Analysis was by intention to treat. At baseline, sexual problems were reported in 14.4% of men and 4.9% of women. Age ≥ 60 years, systolic blood pressure ≥ 140 mm Hg, and previous use of antihypertensive drugs were associated with erectile problems in men at baseline. During follow-up, age and previous use of antihypertensive medication were associated with erectile problems in men; sexual problems in women were rare (5 women [1.5%] reported difficulty in having an orgasm). At 24 months, men taking chlorthalidone had the highest incidence of erectile problems; 15.7% had problems obtaining an erection compared with 4.9% of men taking placebo (P = 0.004). The other 4 groups did not differ from the placebo group. The differences among groups at 48 months did not reach statistical significance because 11 additional patients receiving placebo and 1 additional patient receiving chlorthalidone reported erectile problems at 36 or 48 months.


Chlorthalidone was associated with a higher rate of erectile problems after 2 years than placebo, acebutolol, amlodipine, doxazosin, or enalapril. Sexual dysfunction was rare in women with hypertension.

Sources of funding: National Institutes of Health; Boehringer-Ingelheim; Merck, Sharp & Dohme; Pfizer, Inc.; Wyeth-Ayerst.

For article reprint: Dr. R.H. Grimm Jr., Shapiro Center for Evidence-Based Medicine, 914 South 8th Street, D-5, Minneapolis, MN 55404, USA. FAX 612-347-7761.

*JAMA. 1996;275:1549-56.


To me, the most important observations from the study by Grimm and colleagues were that few patients experienced sexual dysfunction resulting from treatment and that differences among the drugs, despite their varied mechanisms of action, were slight. The patient sample was relatively small, and when it was divided into the 5 drug groups plus 1 placebo group, the numbers in each group reached levels at which major differences were necessary to establish significance. In the study sample, 14% of the men had sexual dysfunction at baseline; this was related to age and occurred in about 18% of patients older than 60 years of age. During the 4-year follow-up period, the incidence increased to only 15%, with some patients improving and others developing problems. The incidence in the placebo group increased, suggesting again that aging was a major factor in the onset of sexual problems.

The statement that chlorthalidone was the major culprit and that doxazosin was associated with the fewest problems is based on relative differences in a situation in which the absolute numbers are small. For example, although 17% of patients receiving chlorthalidone had erectile problems at 24 months, this amounted to only 12 patients; the corresponding figure for placebo was 8%, a 2-fold difference in relative terms but representing only about 5 patients in absolute values. After 4 years, the 5 classes of drugs did not differ and chorthalidone no longer differed from placebo. The evidence of sexual dysfunction in women obtained in this study was too slight to provide any useful information.

What is important in this study is that erectile dysfunction is relatively uncommon, even in older men; that this dysfunction is, to a substantial extent, related to age and not to medication; and that little evidence exists to show that any one of the common drugs creates more problems than another. Further, because of individual variations in both patients and drugs, one can empirically switch agents and sometimes resolve the erectile problem without impairing efficacy.

Alvin P. Shapiro, MD
University of PittsburghPittsburgh, Pennsylvania, USA