RANDOMIZED STUDY OF TESTOSTERONE GEL AS ADJUNCTIVE THERAPY TO SILDENAFIL IN HYPOGONADAL MEN WITH ERECTILE DYSFUNCTION WHO DO NOT RESPOND TO SILDENAFIL ALONE

doi:10.1097/01.ju.0000132389.97804.d7

The Journal of Urology

Volume 172, Issue 2, August 2004, Pages 658-663

https://doi.org/10.1097/01.ju.0000132389.97804.d7 Get rights and content

ABSTRACT

Purpose:

We compare the efficacy of testosterone gel (T-gel) versus placebo as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone.

Materials and Methods:

A randomized, placebo controlled, double-blind, parallel group, multicenter study was performed. A total of 75 hypogonadal men (18 to 80 years old, morning serum total testosterone 400 ng/dl or less) with confirmed lack of response to sildenafil monotherapy were randomized (1:1) to receive a daily dose of 1% T-gel or 5 gm placebo gel as adjunctive therapy to 100 mg sildenafil during a 12-week period. Subjects were evaluated for sexual function, primarily based on the International Index of Erectile Function (IIEF), quality of life and serum testosterone levels at baseline and weeks 4, 8 and 12.

Results:

Testosterone treated subjects had greater improvement in erectile function compared to those who received placebo, reaching statistical significance at week 4 (4.4 vs 2.1, p = 0.029, 95.1% CI 0.3, 4.7). Similar trends were observed for improvements in orgasmic function, overall satisfaction, total IIEF score and percentage of IIEF responders. T-gel significantly (p ≤0.004) increased total and free testosterone levels throughout the study, although no significant correlations were made between testosterone levels and the IIEF at end point.

Conclusions:

T-gel taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who are unresponsive to sildenafil alone.

Section snippets

Study design and population.

This study followed the Declaration of Helsinki (1996) and the US 21 Code of Federal Regulations. Institutional review board approval was obtained before initiation and written informed consent was obtained from each subject. This randomized, placebo controlled, double-blind, parallel group study involved 7 study visits. Visits 1 and 2 (screening) were completed within 14 days of visit 3, visit 3 was on day −28 at the start of the 4-week lead-in period with 100 mg sildenafil monotherapy, visit

Disposition and background characteristics.

The study was conducted from October 2, 2001 to November 15, 2002. A total of 75 subjects (15 centers) were randomized and received at least 1 dose of study gel in conjunction with sildenafil (fig. 1). Seventy subjects were included in the ITT efficacy analyses. Treatment groups were generally well matched with regard to demographic and background characteristics (table 2).

Efficacy findings.

Erectile Function Domain of the IIEF: Mean erectile function domain scores were comparable between groups at baseline (

DISCUSSION

In this study adjunctive use of transdermal T-gel with sildenafil improved sexual activity in hypogonadal men with ED who were unresponsive to sildenafil alone. Improvements over placebo were observed throughout the 12-week period for each domain of the IIEF and the total score. Differences between study groups were most marked after 4 weeks of therapy, reaching statistical significance for improvements in the total IIEF score and 3 of the 5 domain scores (including erectile function). These

CONCLUSIONS

Despite the therapeutic advance of PDE-5 inhibitors, many men with ED do not adequately respond to therapy. More than 20% of subjects screened for our study had low T levels (less than 400 ng/dl). Such levels may contribute to continued sexual dysfunction when treated with sildenafil alone. T-gel (1%) taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with ED who are unresponsive to sildenafil alone. Further studies using T-gel in conjunction with

REFERENCES (10)

RosenR.C. et al.
The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction
Urology
(1997)
MoyadM.A.
The placebo effect and randomized trials: analysis of conventional medicine
Urol Clin North Am
(2002)
NIH Consensus Conference
Impotence. NIH Consensus Development Panel on Impotence
JAMA
(1993)
www.viagramd.com/pi/proPackInsert.asp. Accessed September 17,...
SaloniaA. et al.
Sildenafil in erectile dysfunction: a critical review
Curr Med Res Opin
(2003)

There are more references available in the full text version of this article.

Cited by (318)

Erectile dysfunction in diabetes mellitus
2009, Journal of Sexual Medicine
Type 2 diabetes is reaching pandemic levels and young-onset type 2 diabetes is becoming increasingly common. Erectile dysfunction (ED) is a common and distressing complication of diabetes. The pathophysiology and management of diabetic ED is significantly different to nondiabetic ED.
To provide an update on the epidemiology, risk factors, pathophysiology, and management of diabetic ED.
Literature for this review was obtained from Medline and Embase searches and from relevant text books.
A comprehensive review on epidemiology, risk factors, pathophysiolgy, and management of diabetic ED.
Large differences in the reported prevalence of ED from 35% to 90% among diabetic men could be due to differences in methodology and population characteristics. Advancing age, duration of diabetes, poor glycaemic control, hypertension, hyperlipidemia, sedentary lifestyle, smoking, and presence of other diabetic complications have been shown to be associated with diabetic ED in cross-sectional studies. Diabetic ED is multifactorial in aetiology and is more severe and more resistant to treatment compared with nondiabetic ED. Optimized glycaemic control, management of associated comorbidities and lifestyle modifications are essential in all patients. Psychosexual and relationship counseling would be beneficial for men with such coexisting problems. Hypogonadism, commonly found in diabetes, may need identification and treatment. Maximal doses of phosphodiesterase type 5 (PDE5) inhibitors are often needed. Transurethral prostaglandins, intracavenorsal injections, vacuum devices, and penile implants are the available therapeutic options for nonresponders to PDE5 inhibitors and for whom PDE5 inhibitors are contraindicated. Premature ejaculation and reduced libido are conditions commonly associated with diabetic ED and should be identified and treated.
Aetiology of diabetic ED is multifactorial although the relative significance of these factors are not clear. A holistic approach is needed in the management of diabetic ED. Malavige LS, and Levy JC. Erectile dysfunction in diabetes mellitus. J Sex Med 2009;6:1232–1247.
Testosterone therapy in men with androgen deficiency syndromes: An endocrine society clinical practice guideline
2010, Journal of Clinical Endocrinology and Metabolism
Our objective was to update the guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men published previously in 2006.
The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration.
We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and, in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected by measurement of free or bioavailable testosterone level, using validated assays. We recommend testosterone therapy for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 4 ng/ml or greater than 3 ng/ml in men at high risk for prostate cancer such as African-Americans or men with first-degree relatives with prostate cancer without further urological evaluation, hematocrit greater than 50%, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score above 19, or uncontrolled or poorly controlled heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.
Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations
2008, European Journal of Endocrinology
Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: Correlations with bioavailable testosterone and visceral adiposity
2007, Diabetes Care
The decline of androgen levels in elderly men and its clinical and therapeutic implications
2005, Endocrine Reviews
Effects of testosterone on sexual function in men: Results of a meta-analysis
2005, Clinical Endocrinology

View all citing articles on Scopus

: Supported by Solvay Pharmaceuticals, Inc., the parent company of Unimed Pharmaceuticals, Inc. and manufacturer of the testosterone gel used in this study.
Study received institutional review board approval.

View full text

Adult Urology: Sexual Function/InfertilityRANDOMIZED STUDY OF TESTOSTERONE GEL AS ADJUNCTIVE THERAPY TO SILDENAFIL IN HYPOGONADAL MEN WITH ERECTILE DYSFUNCTION WHO DO NOT RESPOND TO SILDENAFIL ALONE

ABSTRACT

Purpose:

Materials and Methods:

Results:

Conclusions:

Section snippets

Study design and population.

Disposition and background characteristics.

Efficacy findings.

DISCUSSION

CONCLUSIONS

Urology

Urol Clin North Am

Impotence. NIH Consensus Development Panel on Impotence

JAMA

Sildenafil in erectile dysfunction: a critical review

Curr Med Res Opin

Adult Urology: Sexual Function/Infertility
RANDOMIZED STUDY OF TESTOSTERONE GEL AS ADJUNCTIVE THERAPY TO SILDENAFIL IN HYPOGONADAL MEN WITH ERECTILE DYSFUNCTION WHO DO NOT RESPOND TO SILDENAFIL ALONE