Benign prostatic hyperplasia (BPH) and lower urinary tract symptoms are bothersome and costly conditions affecting nearly half of men older than age 50 years and 90% of men older than age 80. In the search for more effective noninvasive therapies, the role of the neural activity in BPH has been studied. Botulinum toxin injection has been used for several urological conditions including voiding dysfunction, and studies have shown that intraprostatic injection may be beneficial in lower urinary tract symptoms secondary to BPH.

Eligible men were randomized in a 1:1 ratio to a 100 or a 300 U dose of onabotulinum toxin A. The study was double-blind as to the toxin dose. The drug was injected transrectally into the prostatic peripheral transitional zone with ultrasound guidance. It was administered as 2 cc per lobe in 1 ml aliquots at 2 injection sites for a total of 4 sites.

Men were contacted by telephone at 1 week after treatment, and evaluated in person at 1, 2, 3, 6, 9 and 12 months. Uroflowmetry, vital signs, AUASI and medical conditions were collected or performed at baseline and each visit; transrectal ultrasound and questionnaires on the impact of BPH, bladder function, erectile function and ejaculatory function were administered at baseline, and 3 and 12 months; bladder ultrasound was performed at baseline and 12 months; and physical and digital rectal examination, and prostate specific antigen were determined at baseline, and at 3, 6 and 12 months.

To determine whether two different doses (100 U and 300 U) of onabotulinum toxin A injection into the prostate gland demonstrate sufficient improvement in the management of lower urinary symptoms due to BPH to warrant more extensive research.

The primary outcome was treatment success at 3 months post-treatment, defined as:

1. Improvement in the American Urological Association symptom index (AUASI) by at least 30% and/or

2. Urinary flow rate (Qmax) improvement of more than 30%, each determined from baseline to 3 months after injection.

In addition, two safety criteria also had to be met. A dose failed if either:

1. Any reported event was determined to be related to the onabotulinum toxin A injection and was considered life threatening, disabling, or fatal

2. ≥ 40% of the participants reported a moderate or severe side effect related to the botulinum toxin injection.

• Male at least 50 years of age
• Voided volume ≥ 125 ml
• Maximum urinary flow < 15 ml/sec
• AUA symptom severity score ≥ 8
• Patient signed informed consent prior to the performance of any study procedures
• Patient able to complete the study protocol in the opinion of the investigator

A total of 134 men were randomized and treated (68 with 100 units, 66 with 300 units), with 131 assessed at 3 months and 108 assessed at 12 months. Each dose met the 3-month primary outcome criteria. In the 100 unit arm the mean baseline AUASI score of 18.8 decreased by 7.1 and 6.9 at 3 and 12 months, respectively. In the 300 unit arm the baseline of 19.5 decreased by 8.9 and 7.1, respectively. In the 100 unit arm the mean baseline maximum urinary flow rate of 10.0 ml per second increased by 2.5 and 2.2, respectively, and in the 300 unit arm the baseline of 9.6 increased by 2.6 and 2.3, respectively. (J Urol. 2011 Sep;186(3):965-70.)