Finasteride improves urinary symptoms obstructive urethra (LUTS) for decreasing the size of the prostate, especially for those larger than 40 grams. Finasteride prevents the Testosterone be transformed into Dihydrotestosterone (DHT), the true intracellular active hormone. However, little is known about what this systemic blockade causes in organs sensitive to the action of testosterone.
There are two 5α-reductase isoforms:
Just to put it in context, hormones are produced by the endocrine glands that act remotely on their target organs. When a check up is done, both TSH, T3 and free T4 measurements are always requested. However, testosterone is poorly evaluated even in men. Women produce around one-sixth of men's testosterone. Knowledge about the action of Testosterone has improved in the last 10 years, not only in the prostate, but also for other organs.
The clinical treatment of alopecia has been with Finasteride 1 mg and prostate adenoma with Finasteride 5 mg or Dutasteride 0,5 mg for many years. They act on testosterone receptors expressed in various organs. Two types of 5α-reductase inhibitors are available for clinical use: Dutasteride and Finasteride. Finasteride inhibits only 5α-reductase type 2, while Dutasteride inhibits both types of 5α-reductase.
They have action on hair, beard, hair, liver, kidneys, male genitals, hematopoietic system, skeletal and cardiac muscle, among others. Testosterone and 5α-DHT play an important role in the regulation of muscle, adipose tissue, liver, bone and central nervous system, as well as in reproductive and sexual functions. The main purpose of Finasteride is improving urinary symptoms.
A Testosterone is transformed by the enzyme 5α-reductase into DHT, which is the active intracellular molecule. Therefore, the main cellular androgen is DHT. Although they are not elevated in HPB, DHT levels in the prostate remain normal with aging, despite the decrease in testosterone. Finasteride suppresses DHT by about 70% in the serum and up to 85-90% in the prostate.
The main objective of the treatment is the enlargement of the blocked urethra caused by the growth of the prostate. In this way, it facilitates the passage of urine. As a result, Finasteride improves symptoms, especially urinary jet strength and bladder emptying. In this way, the detrusor pressure decreases to expel urine from the bladder.
Therefore, there is an interruption of the effects that cause thickening of the detrusor, that is, of the bladder muscle. Thus, he does not need to exert as much force to expel the urine and reduces the bladder residue.
Risk factors for progression of BPH
The risk factors recognized for the progression of HPB are: age greater than 50 years, PSA greater than 1,4 ng / mL, prostate larger than 30 cm3, severity of urinary symptoms (LUTS), decreased urinary flow (Qmax) and obesity. However, there are exceptions to these rules, as there are patients with prostates less than 30 grams that are obstructed. In these patients, in addition to growth towards the urethra of the adenoma, the prostatic capsule is more densely fibrous and, therefore, prevents the accommodation of its growth. In this way, it causes progressive obstruction of the urethra and increases intravesical pressure. Therefore, the detrusor is damaged.
Diabetics and patients with metabolic syndrome should be understood as at-risk patients, as they cause damage to the bladder innervation. Initially, there is a decrease in bladder sensitivity and then in the contractile force of the detrusor. Furthermore, they produce the insulin-like growth factor, IGF-1, in the liver. Insulin resistance occurs by decreasing the response of tissues to insulin.
Hyperinsulinemia increases IGF-1 in the liver. Insulin resistance with secondary hyperinsulinemia is associated with increased HPB. In addition to this action, it increases the activity of the sympathetic nervous system and the smooth muscle tone in the prostate. They occur in the stroma which is the supporting tissue of the prostate that grows most among the glandular acini. So it can worsen urinary symptoms regardless of prostate volume.
A metabolic syndrome is a set of clinical and laboratory changes that predicts the risk of cardiovascular disease and the onset of diabetes. Furthermore, it causes a silent compromise in several organs. Therefore, if not properly treated, it can cause serious damage to health.
A metabolic syndrome it is defined by an increase in blood glucose and insulin resistance, an increase in abdominal circumference associated with the body mass index (BMI), an increase in triglycerides, an increase in total cholesterol and a decrease in HDL and an increase in blood pressure.
The goal of 5-α reductase inhibitors in the prostate is to improve urinary symptoms, reduce prostate volume, increase urinary flow, decrease the risk of urinary retention and reduce the indication for surgery. Symptoms may improve 3 months after starting treatment.
Thus, a treatment period of at least 6 months is necessary to verify its action on the prostate. Its benefits appear slowly. The first evaluation can be done with hair in 4 months. In the best of scenarios, there may be a reduction of around 20-25%.
Aging reduces the urinary stream slowly. Thus, it appears that the average voiding flow decreases from 20,3 mL / sec between 40 and 44 years to 11,5 mL / sec after 75 years of age.
The average improvement in urinary flow compared to the initial assessment is 2,4 mL / sec with the combination (Dutasteride and Tamsulosin), 1,9 mL / sec with Dutasteride and 0,9 mL / sec with Tamsulosin (medicine that opens the prostatic urethra and facilitates the outflow of urine).
The person who urinates well has a voiding flow greater than 15-20 mL / sec. So that patient who has an initial flow of 9 mL / sec, may even notice an improvement in symptoms, but is still living with a flow below the desired. If the intravesical pressure continues to increase, the bladder is not yet relieved and the lesion on the detrusor persists. Consequently, detrusor thickening may worsen.
The person who already has a detrusor thickening greater than 5 mm has a worse clinical response with the use of medications. Your answers are significantly worse. Thus, they present a decrease in several urinary parameters, when evaluated by their symptoms and tests that quantify them, when compared to the one with normal detrusor.
This patient should be evaluated with greater care, as clinical improvement can happen, but without functional improvement. Therefore, you will still be at risk of HPB and worsening of the detrusor. In this obstructed patient, the pressed detrusor turns into fibrosis, with loss of bladder elasticity, that is, decreasing its capacity to store urine.
The bladder is like a rubber band, if the muscle gets thicker, it decreases its elasticity. Likewise, the bladder gets smaller.
5α-reductase inhibitors induce the death of prostate epithelial cells leading to a reduction in size of about 18-28%. However, there is a decrease in PSA around 50% after six to twelve months of treatment.
The maximum effect of Dutasteride on DHT reduction is observed in 1 or 2 weeks. After 1 week, serum concentrations of DHT showed a reduction of 85% and after 2 weeks, of 90%. The reduction of DHT it was 94% after 1 year and 93% in 2 years.
The most expressive and widespread side effects are around 1-10%. Erection difficulties, decreased libido, changes in ejaculation (reduced semen volume and retrograde ejaculation) and breast enlargement were the most frequent. However, in a small number of people, these side effects continue after treatment is stopped. But the reason is unknown.
In the multicenter, specific study on the effects on sexuality, double-blind and placebo-controlled, PROWESS evaluated for 2 years, the long-term effects of Finasteride in men aged 50 to 75 years with moderate BPH. Of the 3.168 participants, there was a change in libido, ejaculation disorder, impotence or orgasm dysfunction in 10% of the Finasteride group versus 7% in the placebo.
The discontinuation rate was the same for the groups (1%). But, the small increase in sexuality-related side effects was associated with the drug. However, they consider long-term treatment to be well tolerated and effective.
Decreased libido, ejaculation disorder and impotence were reported in 4, 2,1 and 6,6%, respectively, in the Finasteride group, compared with 2,8, 0,6 and 4,7% for the control. However, only ejaculation and impotence disorders showed significant differences between groups (p <0,05).
All these negative effects are happening slowly and it ends up being incriminated to aging, as they get worse after 3 to 4 years. Certainly, there is a worsening in the quality of erection, drop in testosterone and consequently the quality of life of these patients.
Clinically, Finasteride improves urinary symptoms by decreasing the number of times a patient has to go to the toilet and waking up at night to urinate. When these drugs are indicated, the doctor usually tells the patient that they should be used for life to maintain their effects. However, this statement is being questioned. Its indication should be made only for patients with prostate is more bulky, therefore larger than 40 grams.
Clinical improvement starts after 4 months of use and can reach a maximum of 1,5 to 2 years. However, at 12 months it reaches 90%. Therefore, when administering this treatment, the patient must be evaluated with imaging tests after 4 months. Then, exams are held between 6 and 8 and thereafter annually. However, if there is no improvement after 6 months, it is understood that the patient is not a good responder and the medication should be discontinued. Thus, the surgery it should be indicated and it must be the main treatment.
In the PLESS study, with a 4-year follow-up, 13,2% of patients treated with placebo had a need for surgery or acute urinary retention, compared with 6,6% of patients treated with Finasteride. Therefore, there was a 51% reduction in the risk of surgery or acute urinary retention compared to the placebo group.
Finasteride reduced the risk of surgery by 55%, from 10,1% for placebo versus 4,6% and reduced the risk of acute urinary retention by 57%, from 6,6% for placebo versus 2,8%. The risk reduction was evident between the groups in the first assessment at 4 months and was maintained for the 4 years of the study.
Finasteride and Dutasteride are drugs that prevent the conversion of serum testosterone to DHT by 5α-reductases (5α-Rs). DHT is ten times more potent than testosterone, being the active form of the intracellular androgen. On the other hand, 5α-Rs are a family of several enzymes that play an important role in physiology, regulating the cellular metabolism of androgens, glucocorticoids and steroids. Thus, they modulate mitochondrial function, metabolism of carbohydrates, proteins and lipids and energy balance.
A Testosterone it regulates muscle growth, bone and brain metabolism, and the formation of red blood cells. In addition, the liver functions, the epithelium of the vessels, the hair and hair, and the function and inhibition of the formation of body fat. In the embryonic period, it has a fundamental role in sexual differentiation and in adolescence it is the main responsible for the spurt of genital and body growth.
However, if you would like to know more about this and other diseases of the genitourinary tract, access our content area for patients to understand and gain knowledge. There are more than 140 articles on various urological subjects available for your reading. Culture always makes a difference. You will be surprised!
Urinary retention in patients with BPH treated with finasteride or placebo over 4 years. Characterization of patients and ultimate outcomes. The PLESS Study Group. https://pubmed.ncbi.nlm.nih.gov/10765090/
Long-term treatment with finasteride improves clinical progression of benign prostatic hyperplasia in men with an enlarged versus a smaller prostate: data from the MTOPS trial. https://pubmed.ncbi.nlm.nih.gov/21334655/
European Urology association. https://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/