Study: Tadalafil Recommended for Men with ED and BPH/LUTS, Regardless of Total Testosterone Levels

Study: Tadalafil Recommended for Men with ED and BPH/LUTS, Regardless of Total Testosterone Levels

Impact of Baseline Total Testosterone Level on Successful Treatment of Sexual Dysfunction in Men Taking Once-Daily Tadalafil 5 mg for Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: An Integrated Analysis of Three Randomized Controlled Trials

John P. Mulhall, MD; Gerald B. Brock, MD; Sidney Glina, MD; Simin Baygani, MS; Craig F. Donatucci, MD; Mario Maggi, MD

ONLINE: May 2016 – The Journal of Sexual Medicine

DOI: http://dx.doi.org/10.1016/j.jsxm.2016.02.163


Introduction

Older men with benign prostatic hyperplasia (BPH – an enlarged prostate) often experience erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Testosterone is linked to ED, but it is unclear how it how testosterone deficiency affects LUTS.


The researchers concluded that baseline total testosterone levels do not impact the response of tadalafil in these men.


Past studies have found that men with low levels of total testosterone do not respond well to phosphodiesterase type 5 inhibitors (PDE5i’s - oral ED medications). The situation might improve after testosterone replacement therapy (TRT). However, other studies suggest that that is no link between TRT and ED improvement with these drugs.

The current study investigated whether baseline hormone levels play a role in sexual response to the PDE5i tadalafil in men with LUTS-BPH and ED.

The researchers concluded that baseline total testosterone levels do not impact the response of tadalafil in these men.

Methods

The study was based on data from three earlier studies of men with LUTS-BPH. Each study began with a 4-week lead-in period followed by a 12-week double-blinded treatment phase. Five hundred forty men received tadalafil 5 mg once daily. The remaining 535 men were given a placebo.

Men who were sexually active completed the International Index of Erectile Function (IIEF) at baseline (after the lead-in period but before the treatment phase) and again at the end of the 12-week treatment period. Total testosterone (TT) levels were measured at baseline, along with luteinizing hormone (LH), and estradiol.

None of the men had had TRT in the past.

Results

The present analysis included 1,049 men with baseline TT levels and 1,058 men with baseline LH levels. On average, they were between 64 and 70 years old.

At baseline, over 79% of the men self-reported ED, and about two-third of them said their ED had been moderate to severe for at least a year. Baseline characteristics were similar for both the treatment and the placebo groups.

The average baseline TT level was 355.1 ng/dL. Hypogonadism, defined as TT below 300 ng/dL, was diagnosed in 32.4% of the men.

Men with low TT levels were more likely to have diabetes, cardiovascular disease, and hypertension when compared to men with normal TT levels.

Data on sexual function changes, measured by the changes in IIEF scores, was available for 900 men. After the 12-week treatment period, tadalafil was “significantly” more effective than placebo for most IIEF domain scores. The drug was also more effective than placebo regardless of TT level.

Discussion

“The findings of this integrated analysis challenge previous reports suggesting that normalizing testosterone levels is essential toward achieving a response to PDE5i therapy in men with low TT levels,” the authors wrote, adding, “Our analysis corroborates and extends previous reports supporting that low androgen levels do not compromise PDE5i efficiency.”

They did acknowledge some limitations. For example, only one TT measurement was taken – at baseline - and levels could vary based on the assay used. Only TT levels were analyzed, so it is unknown how free testosterone could affect the men’s response to PDE5i therapy. Also, only one tadalafil dose – 5 mg once daily – was investigated. Other doses might have yielded different results.

More research is needed on men with very low TT levels, the authors noted.

They recommended that clinicians consider starting PDE5i therapy after a patient’s first visit for ED. “There is no need to wait for confirmation of a normal serum testosterone level. TRT as a supplement to PDE5i therapy should be reserved for those patients whose clinical laboratory values repeatedly confirm low serum testosterone levels and who have demonstrated a suboptimal therapeutic response,” they explained.