Generic Tadalafil In The Treatment Of BPH: Therapeutic Evidence

What is benign prostate benign prostatic hyperplasia?

Benign prostatic hyperplasia, sometimes referred to as enlarged prostate, is a condition during which the overall size of the prostate gland is magnified. Why is it benign? Simply, because it does not belong to cancer conditions, nor it can cause any cancer or become a risk-factor for it.

benign prostatic hyperplasiaWhy it is dangerous then? The problem with the prostate is when it grows to be large enough; it can physically press onto the urethra. When urethra is pressed on, consequently, it cannot function longer normally, while the urine flow gets suppressed or even altogether blocked in. This condition, in its turn, can become a cause of a wide variety of complications with urination, or, in extreme case, can cause very dangerous urinary tract infection.

What is the function of the prostate gland?

The prostate is the gland which is approximately the size of a walnut that belongs to the male reproductive system. It is wrapping the first portion of the urethra. Above the prostate, the urinary bladder is situated. It functions as a manufacturing unit for the production of a milky fluid that flows from the urethra and is later fused with spermatozoa when the ejaculation occurs. This milky fluid’s primarily function is providing needful nutrition for the sperm. It also works as an excellent natural lubricant.

What men are affected by benign prostatic hyperplasia?

Benign prostatic hypеrplasia affects aging men more than younger men. As a matter of fact, it is estimated to be more than fifty percent of male over the age of sixty having an enlarge prostate. Around half of men who belong to this group show clinically bad symptoms.

What causes benign prostatic hyperplasia?

Benign prostatic hyperplasia can be caused by a variety of factors or a combination of those. One of the significant factors causing BPH is actually normal hormonal change that occurs in men while they age. Inside the aging prostate tissue, the ratio of the proliferation of cells that are targeted and induced by hormones may exceed the usual, preprogrammed rate of cell death. As a result of this miscalculation, there is a larger number of cells than it was supposed to be inside this part of the male organism. The tissue gets growing larger and larger.

How can benign prostatic hyperplasia be treated?

The medical specialists usually refer to three general classes of meds when dealing with the treatment of benign prostatic hyperplasia.

  1. The oldest treatments available are alpha-blockers. These medications are good in relaxing muscles in the prostate as well as around the bladder neck area. When the muscles are relaxed, the urine can flow smoothly and the balance is restored to normal again.
  2. 5-alpha reductase inhibitors. These essentially inhibit the overall local production level of dihydrotestosterone, which is the hormone primarily responsible for prostate enlargement.
  3. Reversible phosphodiesterase type 5 inhibitor, such as tadalafil.

For patients, who are not responsive to the above three major groups of medications, the minimum invasive procedures are available.

Let’s focus on tadalafil efficacy in the BHP treatment

What is tadalafil?

Tadalafil belongs to a class of reversible phosphodiesterase-type 5 inhibitors. The medication is traditionally packaged in an oral pill and is available in a variety of dosages: 2,5 mg, 5 mg, 10, mg, 20 mg. In its generic versions, tadalafil can be available at other dosages as well.

What is tadalafilWhile envisioned, manufactured and marketed as a treatment for ED in men primarily, tadalafuil has shown efficacy in treatment of benign prostatic hyperplasia and granted an authorization as a treatment for this condition as of 2012. While the accurate place of tadalafil’s in BPH therapy is yet to be established, there are positive indications that tadalafil can become the primary option for treating the condition among all available on a today’s pharmaceutical market.

The summary of evidence of treatment of BPH with tadalafil

The available studies that were conducted to establish the efficacy of treatment of BPH in men show the following positive results: A large group of men were trialed with tadalafil in a classic, double blind, placebo controlled, dose finding study. For twelve weeks, the group of men were treated with placebo or tadalafil (5 mg). The findings upon the end of the treatment showed that daily 5 mg dosage of tadalafil administered improved the lower urinary tract symptoms compared to those with placebo on average at 2.6 points according to the recognized world-wide prostate symptoms score coefficient. It should be noted that while the primary benefits of administering tadalafil were observed within the first twelve weeks of treatment, these were maintained to a smaller degree for a larger timeframe (six months to twelve month).

Is there a connection between erectile dysfunction and BHP?

Erectile dysfunction (disease page) and lower urinary tract symptoms, where BHP belongs, in general considered to be very prevalent conditions that are affecting the overall quality of a male’s life negatively. While these two conditions had been considered separated from one another for a significant period of time, however, due to the increasing number of clinical researches and gathered data, the two conditions have become linked from the point of view of modern medicine as they share several comоrbidies and also have a similar impact on one’s lifestyle.

Major shared pathways between ED and BHP

There are four major ways on evaluating how pathways are shared between ED and BPH.

  1. The shared impairness of the synthase of nitric dioxide while in the endothelium of the pelvic area. The latter includes the prostate, the bladder, and the smooth muscles of the penis.
  2. A known increase of Rho-kinase activation which in its turn manifests in the decreased relaxation in muscles. As a result, the outlet resistance of the bladder gets magnified while a possibility to get a healthy erection gets lower.
  3. There is a connection between an autonomic hyperactivity as well as accompanied metabolic syndrome effects on the growth of the prostate and erectile dysfunction.
  4. Consider atherosclerosis as a common precursor for BHP and erectile dysfunction. Atherosclerosis is known to significantly reduce nitric dioxide production as well as Rho-kinase activation and usually causes the overall loss of smooth muscles from the area of the bladder detrusor and prostate fibrosis commonly linked with the overall decreased bladder compliance.

To add, all four ways are accompanied by the impairment of vascular function.

What is the clinical evidence of effects of tdalafil on the common pathways of erectile dysfunction and BPH?

There are two important mechanisms that play role in decreasing the tension in smooth muscles of the bladder as well as the penis: the reversal of norepinephrine and endiothelin tissue constriction and an anti-proliferative effect on muscle cells in the prostate and in the bladder.

  • Tadalafil, as PDE5 inhibitor has greater activity when compared to sildenafil citrate or vardanafil in the overall relaxation level of the above mentioned smooth muscles. Across the family of PDE5 inhibitors, only tadalafil showed results in relaxation of the smooth muscles in the bladder and prostate of more than fifty percent on the pre-contracted strips.
  • Tadaladil causes an inhibitory effect on nitric оxide among ion channels across afferent neurons (sensory pathways) as well as on afferent activity of nerves in the bladder.
  • Tadаlafil have a potential of inhibiting in vitro activity of PDE5, which is manifested in the vesicular-deferential arteries and increased oxygenation into the prostate tissue.
  • Tаdalafil increases prostatic blооd perfusion.
  • Tаdalafil lessens the amount of expression of a variety of inflammatory markers and has a potential of reducing atherosclerotic overall damage as well as inflammation by way of decreasing leukocyte recruitment significantlyю

Tаdalafil’s mechanism of action in relation to BHP:

  1. Upregulating nitric oxide/ cycle GMP activity
  2. Downregulating Rho-kinase activity
  3. Modulating autonomous nervous system over-activity and afferent nerve activity
  4. Increasing pelvic perfusion and reducing ischemia
  5. Reducing inflammation

Is taking tadalafil safe for patients with BHP?

The clinical studies have shown that tadalafil is a very safe treatment.

There are side effects of taking tadalafil which include:

  • Mild headache
  • Dyspepsia
  • Nasal congestion
  • Face flushing
  • Mild back pain

The incidents of these are varied from 1 percent to 3 percent among the patients in the control group.

Is it safe to combine α-adrenergic antagonist with tadalafil?

The studies have shown that all patients who alpha-blockers with tadalafil 5 mg were stable. It is generally considered to be a healthy combination of two powerful medicines. However, the further study needs to be done for the specific type of alpha-blockers, most notably those taking doxazosin and other nonuro-selective alpha-blockers. There is some evidence that men who take these when combined with tadаlafil treatment show increased hemodynamic signs and symptoms.