Men with low testosterone who don’t respond initially to PDE5 inhibitors may benefit from longer trials of once a day tadalafil or the addition of testosterone therapy.

The PDE5 inhibitors have been a valuable tool in the treatment of men with erectile dysfunction (ED).  Many men pin a lot of hopes on tablets restoring their sexual capacity and the disappointment can be great if they discover they don’t work for them as expected.  Yet about 30-35% of patients fail to respond initially to PDE5 inhibitors In addition, uncontrolled studies have shown that testosterone deficiency predicts a poor response to sildenafil and tadalafil and addition of testosterone can help. This double-blind placebo controlled trial investigates how initial non-responders to the PDE5 inhibitor tadalafil can be helped by every day dosing, and the threshold of baseline testosterone for which the addition of testosterone gel may improve response.

The multicentre trial followed 173 men aged 45-80 who had initially not responded to tadalafil on four separate occasions.  All suffered ED for over 3 months and were in stable heterosexual relationships.  Early morning blood samples showed serum total testosterone levels less than or equal to 4ng/mL and/or bioavailable testosterone less than or equal to 1ng/mL.

The men were all given a four week treatment of 10mg once a day tadalafil monotherapy.  Randomisation into two parallel groups followed with participants receiving either additional testosterone gel replacement or a placebo gel.  Follow up investigations were done at 4, 8 and 12 weeks after combined therapy started.  Erectile function was assessed using the erectile function domain score (EFD) of the International Index of Erectile Function (IIEF) and the Sexual Encounter Profile (SEP).

223 men entered the first part of the study receiving once a day tadalafil alone.  During this period the mean scores of the EFD went from 12.9 +/– 4 at baseline to 17.4 +/- 6 at four weeks.  17% of the men became responsive to the drug and 14.6% recovered ‘normal’ erectile function.  173 men went on to randomisation, 87 in the test group receiving additional testosterone gel and 86 receiving placebo.  Both groups were matched for age, ED duration and other factors that may affect their erectile function.

Erectile function scores increased in both arms of the randomisation suggesting that once a day tadalafil monotherapy alone can continue to help non responders with low testosterone levels over a twelve week period.  In the combination treatment arm, erectile function scores significantly increased compared to the placebo group, in men with initial testosterone levels less than 3ng/mL.  The lower the baseline testosterone, the lower the improvement with tadalafil alone supporting, the hypothesis that the efficacy of PDE5 inhibitors is androgen dependent.

This study suggests that tadalafil once a day can help many men not responding to initial PDE5 inhibitors over the 12 week period of the study.  This prolonged effect may have clouded the results obtained by addition testosterone gel but it does appear that men with a total serum testosterone level less than 3ng/mL may benefit from the addition of testosterone treatment. 

The study highlights the potential value of routine early testosterone measurements in men with erectile dysfunction, not only to identify a cause for their erectile difficulties but to predict their response to PDE-5 inhibitors and ensure optimum dosing.  Every day tadalafil is also a good option for men with long standing ED.  This study used 10mg every day tadalafil but currently only a 5mg preparation is available.  A similar study needs to be done to see if the results are repeated using this lower dose.

 

Buvat J, Montorsi F, Maggi M et al.  Hypogonadal Men Nonresponders to the PDE5 Inhibitor Tadalafil Benefit from Normalization of Testosterone Levels with a 1% Hydroalcoholic Testosterone Gel in the Treatment of Erectile Dysfunction (TADTEST study).  J Sex Med 2011; 8 : 284-293.

 

 

Filed under: MedicinePosted at 21:49

Tweet

Leave your comment