Correspondence

Finasteride for Benign Prostatic Hyperplasia

N Engl J Med 1993; 328:442-443February 11, 1993

Article

To the Editor:

In my primary care internal medicine practice, the most common symptoms that I hear of from men with prostatic hyperplasia are nocturia and urinary frequency. Could Dr. Gormley and his colleagues (Oct. 22 issue)1 comment on why these symptoms were not included in their symptom questionnaire? In addition, although I would like to ameliorate the symptoms of the disorder in my patients, I find it difficult to decide which ones should be treated with finasteride. Did the authors find that men with any particular group of symptoms and signs were more likely to respond to finasteride?

D. Michael Geller, M.D.
Nalle Clinic, Charlotte, NC 28262

1 References

1. 1

   Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med 1992;327:1185-1191
   Full Text | Web of Science | Medline

To the Editor:

In the study by Gormley et al., the decrease in prostatic volume appeared to level off after six months of treatment with finasteride. Is there a limit to the decrease in prostatic volume -- and in symptoms -- that can occur? Did prostatic volume increase after finasteride was stopped, as occurred in men treated with this drug for a shorter period1?

The urinary flow rate depends on detrusor strength as well as outlet resistance. In previous studies of the relation between flow rate and age, the study subjects were not characterized urodynamically with respect to the presence of either prostate obstruction or impaired detrusor contractility2,3. Although prostate growth may result in both obstruction and secondary detrusor decompensation, systemic disorders and medications also may affect detrusor and outlet function and are frequently not excluded as factors3. Thus, the decline in urinary flow rate with age may represent not only the natural history of prostatic hyperplasia3 but also an age- or disease-related decrease in detrusor contractility. With this in mind, might it not be premature for Gormley et al. to conclude that an improvement of 3 ml per second in the flow rate in men treated with finasteride “represents a shift of about 15 years in the natural course of the disease”?

In view of the common discordance between statistical significance and clinical importance, do the authors have information on the patients' global satisfaction and their quality of life, and can they tell us the number of men who chose to continue taking finasteride after the study ended?

Catherine E. DuBeau, M.D.
Brigham and Women's Hospital, Boston, MA 02115

3 References

1. 1

   Stoner E. The clinical effects of a 5α-reductase inhibitor, finasteride, on benign prostatic hyperplasia. J Urol 1992;147:1298-1302
   Web of Science | Medline

2. 2

   Jorgensen JB, Jensen KM, Mogensen P. Age-related variation in urinary flow variables and flow curve patterns in elderly males. Br J Urol 1992;69:265-271
   CrossRef | Medline

3. 3

   Drach GW, Layton TN, Binard WJ. Male peak urinary flow rate: relationships to volume voided and age. J Urol 1979;122:210-214
   Web of Science | Medline

To the Editor:

I am concerned with the characterization of the effects of finasteride on sexual function in the abstract of the article by Gormley et al. as “a slightly increased risk of sexual dysfunction.” The authors do not say how sexual function was assessed. Were the men asked explicit questions about sexual function each month, did each man complete a symptom questionnaire, or were reports of sexual dysfunction based on responses to a general question about side effects? These three methods can result in different levels of completeness in assessing a problem1.

In addition, the side effects relating to sexual function were not analyzed or discussed in relation to the individualized risk and the effect on the quality of life. The impact of these side effects in any individual man will depend on his base-line level of sexual activity and the degree to which any sexual dysfunction causes distress2,3. Men who were sexually active before the study were probably more likely to have sexual dysfunction during treatment with finasteride than those who were not active. Was base-line sexual activity assessed in this trial? Can the occurrence of sexual dysfunction during the study be related to the base-line level of sexual activity or to other factors, such as age, the presence of other medical problems, or the use of other medications? Answers to these questions would help put the authors' conclusion into better perspective.

Brent A. Blumenstein, Ph.D.
Fred Hutchinson Cancer Research Center, Seattle, WA 98104

3 References

1. 1

   Sugarbaker PH, Barofsky I, Rosenberg SA, Gianola FJ. Quality of life assessment of patients in extremity sarcoma clinical trials. Surgery 1982;91:17-23
   Web of Science | Medline

2. 2

   McSweeney AJ, Labuhn KT. Chronic obstructive pulmonary disease. In: Osoba D, ed. Effect of cancer on quality of life. Boca Raton, Fla.: CRC Press, 1991:105-11.
   

3. 3

   Sherbourne CD. Social functioning: sexual problems measures. In: Stewart AL, Ware JE Jr, eds. Measuring functioning and well-being: the Medical Outcomes Study Approach. Durham, N.C.: Duke University Press, 1992:194-204.
   

Author/Editor Response

The authors reply:

To the Editor: Dr. Geller asks about whom to treat. We found that significant improvement occurred in men with mild, moderate, and severe symptoms; no a priori characteristic helped predict the response to therapy. Nighttime urinary frequency, which was evaluated but not included in the symptom score, decreased as compared with base-line values in the men treated with finasteride, but was not different from that in the men in the placebo group.

Clinical studies of finasteride in the treatment of benign prostatic hyperplasia now include more than 3000 men. On the basis of the results available to us, the effects reported after one year are sustained. Eighty-one percent of the men in our study who received finasteride for 12 months elected to continue treatment, and 64 percent completed 24 months of treatment. After 24 months, their median prostatic volume was reduced by 25 percent and maximal urinary flow was increased by a mean of 2.3 ml per second; 50 percent had an increase of 3 ml per second or more. Moreover, the mean symptom score improved by 3.3 points, which is approximately half the effect produced by transurethral resection of the prostate, as assessed by the same validated questionnaire. The incidence of global satisfaction (i.e., whether the patient was better after finasteride therapy) at one year was higher in the finasteride-treated men than in the placebo-treated men on the basis of ratings by either patients or physicians.

Base-line sexual function was not assessed in detail. The side effects reported were those identified by the patients and considered by investigators to have some relation to treatment. The low reported incidence of sexually related side effects remained constant, with reversal of the effects in some men despite continued treatment. Among men who have undergone transurethral resection of the prostate, 3 to 35 percent become impotent.1

Glenn J. Gormley, M.D., Ph.D.
Elizabeth Stoner, M.D.
Eve E. Slater, M.D.
Merck Research Laboratories, Rahway, NJ 07065

1 References

1. 1

   Roehrborn CG, McConnell JD, Eddy DM. Outcome analysis after treatment for benign prostatic hyperplasia (BPH) by various modalities -- a confidence profile analysis. J Urol 1991;145:Suppl:364A-364A abstract.