Tadalafil tied to urethral smooth muscle relaxation in healthy women: Study

Denmark: Single-dose Tadalafil in healthy women decreases opening urethral pressure (OUP) during resting and squeezing parameters with no differences in voiding parameters. The study drug-induced relaxation of urethral smooth muscle and the external urethral sphincter in healthy women.

The findings of the study were presented at the International Continence Society's 2022 annual meeting (ICS 2022) in Vienna, Austria. 

Urethral pressure is impacted by extensive vascular plexus encompassing the female urethra. Decreased urethral pressure leads to urinary incontinence. The local increase in arterial blood flow induced by the expansion of the vascular plexus could be a potential strategy to treat urinary incontinence. This pharmacological action of vasodilation mediated by phosphodiesterase-type 5 (PDE5) inhibitor action could expand urethral vasculature.

PDE5 is expressible in female reproductive organs, male genital and bladder tissue. Preclinical studies indicate increased baseline urethral pressure following PDE5 inhibition in female rats. The literature also mentions relaxation of urethral smooth muscle and the external urethral sphincter associated with PDE5 inhibition causing micturition. The studies of PDE5 inhibition in female urinary tracts remain clear. Datta et al. could not evaluate significant findings in voiding parameters of sildenafil, 50 mg twice daily for four weeks, in women with obstructed bladder outflow.

Based on the above background, Thea Christoffersen and colleagues from the University of Copenhagen in Denmark conducted a randomized, placebo-controlled trial to evaluate the effects of Tadalafil on OUP.

24 healthy women with a median age of 24.5 and a median body mass index of 22.7 received 40 mg of Tadalafil at the first visit. This was then crossed over to the opposite treatment at the second visit, separated by a washout period of 6 days to avoid carry-over effects.

The key pointers from the study include:

• Urethral pressure reflectometry measured OUP during resting and squeezing conditions of the pelvic floor. This was done after 2 hours of medication in the peak plasma drug concentration.

• Immediately after the above step, uroflowmetry with a prefilled bladder volume of 300 ml natrium chloride was performed.

• Single dose tadalafil 40 mg significantly decreased resting OUP of 6.8 cmH20 and 8.8 cmH20 during squeezing, compared to placebo.

• No significant changes associated with voiding parameters were observed after Tadalafil usage compared with placebo.

• A statistically significant period effect for average flow rate and the maximum flow rate was observed with more increase at the second visit.

• Headache was the most common adverse event associated with Tadalafil use.

The researchers concluded, "Tadalafil induces relaxation of urethral smooth muscle and the External urethral sphincter by nitric oxide pathway, observed as fall in OUP. The effect of PDE5 activity in urethral vascular pressure is negligible, or the mean decrease in urethral pressure during rest and voluntary contraction is the net result of the simultaneous processes."

The authors wrote," Healthy women already have free flow and could explain the reason for lack of significant effect of Tadalafil on voiding parameters."

References:

Christoffersen T, Riis T, Kornholt J, Sonne D, Klarskov N. The effect of single-dose tadalafil on urethral pressure and voiding parameters: a double-blind, randomized, placebo-controlled, crossover study in healthy women. Presented at: ICS 2022, September 7-10, Vienna, Austria. Abstract 3.