Below is an extract from an interesting study on the influence of Finasteride 5 mg (Proscar ®  and other similar drugs) on the development of prostate cancer, and which also causes patients to doubt before taking finasteride for a pathology related to hair care.

What does this article presented by the New England Journal of Medicine (NEJM) for the users of finasteride 1 mg (Proscar ®  and other similar drugs) ? The study about Prevention of Prostate Cancer presented its conclusions about the affect of consuming 5 mg finasteride on the development of prostate cancer in the July 17-2003 edition of NEJM:

A random study, controlled by placebo was carried out over 7 years and which finished in 2003. 18.882 men of more than 55 years old, with normal prostates and PSA levels, were treated with finasteride to determine of the medicine which millions of men take for prostate enlargement, could prevent or retard the appearance of prostate cancer in a population that is more susceptible to this kind of cancer.

Results of the study

The global occurrence of prostate cancer in men treated with finasteride was 24.8% lower than that expected for men of that age-group and medical conditions. This indicates that finasteride 5 mg is effective in preventing or retarding the development of prostate cancer.In men who developed prostate cancer during the study, finasteride 5 mg was associated with a small increase in the risk of developing a cancer of greater malignancy. The reason for this small increase is unknown.

What the study means for those who use finasteride 1 mg

The results of this study (use of 5 mg finasteride for the treatment of prostate enlargement) cannot be generalised for patients taking a dose of finasteride 1 mg to treat hair loss due to androgenic alopecia. The tests performed on finasteride 1 mg have been accepted by the FDA as a safe method of treating hair loss.

History and Introduction

On the 17th of July, 2003, the prestigious New England Journal of Medicine published “The influence of finasteride on the development of prostate cancer”, an article which reported on the results of a multicenter study which lasted for 7 years. The purpose of this study was to test the hypothesis that finasteride 5 mg, used for the treating enlargement of the prostate gland, could reduce the risk of prostate cancer, a high-risk cancer and frequent in men, especially in older men.

The “good and bad news” about the results of the study were well covered by the news media, although they were often badly interpreted. Even though the study was performed on the 5 mg dosage of finasteride and refers only to the prevention of prostate cancer, the results of the study have given rise to questions from both patients and professionals about the use of finasteride 1 mg for the treatment of hair loss. The ISHRS (International Society of Hair Restoration Surgery) believe that the questions raised about the results from the study related to the use of 1 mg finasteride should be considered, but that the questions and also the answers should be based on 1) the facts as demonstrated by the researchers and 2) the interpretation of the results of the study as informed by the researchers.

Why was the study carried out?

The masculine hormone testosterone (androgen) and its most powerful metabolite dihydrotestosterone (DHT) are known to influence in the abnormal growth of the tissue of the prostate gland. When the abnormal growth is benign, the result is the enlargement of the prostate (hypertrophy) and the associated symptoms, such as urine retention. When the abnormal growth is malignant, then the result is prostate cancer.

Finasteride inhibits the enzyme which converts testosterone into dihydrotestosterone thereby reducing the amount of DHT in the body and also the amount which can act on the prostate tissue. Finasteride 5 mg is prescribed to treat benign enlargement of the prostate gland.

The researchers designed the study to establish if finasteride in doses of 5 mg (whose effectiveness has been more than demonstrated in the treatment of benign enlargement of the prostate) can also be effective in preventing or retarding the development of malignant growth in the prostate tissue (prostate cancer). The androgens have many effects on many different tissues and organs, amongst these the hair follicle. The dihydrotestosterone plays an important part in baldness due to androgenic alopecia. And finasteride in 1 mg doses is prescribed as a treatment to diminish its effects.

Proscar and Propecia (and others): same drug but different uses

It is important to emphasize that this medical investigation only studied the effects of 5 mg finasteride. This dosage is commonly prescribed for benign prostate hyperplasia (BPH). Finasteride in 1 mg dosage is commonly prescribed for the treatment of hair loss due to androgenic alopecia (AGA), but it was not used in the study and so was not discussed by the researchers. Many newspapers, television and internet media have not made this distinction when transmitting information, which led to much confusion about the results of the investigation.

The protocol of the study: Who was studied and for how long? The Study on Prevention of Prostate Cancer was a pilot investigation, random and controlled with a placebo (what the Americans call Gold Standard) to obtain objective results. The investigation was carried out in ten medical centres over a period of seven years and concluded in February, 2003.

It was performed with using a broad sample base: 18.882 men, randomly selected, and all of the age of 55 or years or over. All candidates had normal prostate which was confirmed by a physical examination and a prostate-specific antigen (PSA) level of 3.0 ng/ml or less, which indicates that there was no prostate enlargement present (benign or malignant).Half of the men were administered 5 mg of finasteride daily and the other half received the inactive placebo every day during the seven years of the study. The medical and laboratory examinations were performed at regular intervals, and a biopsy of the prostate was performed if indicated necessary by the results of the examinations. All of the men received a biopsy of the prostate at the end of the study. The researchers assumed that 60% of the men would have a provisional diagnostic for prostate cancer during the study or would undergo a biopsy at the end of the study to detect or rule out the presence of cancer.

Results of the investigationThe study was completed in February of 2003, 15 months early, when the researchers found that all of the objectives of the study had been achieved.

At the end of the study, 9,060 men were available for the final analysis: 4,368 had been taking finasteride and 4,692 had been taking the placebo. The final analysis demonstrated the following for each group:

The Finasteride group                                      

• 4,692 men were in the final analysis▪Number of patients with prostate cancer: 1,147 (24.4%).
• Occasions of prostate cancer of greater malignancy:  5.1% of the 4,692 men in the final analysis (22.2% of the 1,068 cancers stated).
• Medical issues and side-effects: the appearance of symptoms in the urinary tract was more frequent in the placebo group.
• Deaths in the study group: 5 deceased during the seven years. ▪See the complete study in NEJM for more details.
• Consult the complete study in NEJM for more details.

The placebo group

• 4,692 men were in the final analysis▪Number of patients with prostate cancer: 1,147 (24.4%).
• Occasions of prostate cancer of greater malignancy:  5.1% of the 4,692 men in the final analysis (22.2% of the 1,068 cancers stated).
• Medical issues and side-effects: the appearance of symptoms in the urinary tract was more frequent in the placebo group.
• Deaths in the study group: 5 deceased during the seven years. 
• See the complete study in NEJM for more details. ▪Consult the complete study in NEJM for more details.

What do the results mean?

• Reduction of prostate cancer incidents.
• The risk of prostate cancer in the USA is 16.7% At the end of the study, the incidence of prostate cancer in the finasteride group had been reduced by 24.8% – a finding which the investigators interpreted as reliable proof that 5 mg finasteride may prevent or retard the appearance of prostate cancer in men older than 55 years who show no signs of cancer before beginning to take the medication. The investigators stated that this finding had an overall beneficial effect. 
• The enigma of malignancy
• Of the 4,368 men who were administered finasteride, 6.4% were diagnosed with prostate cancer of considerable degree of malignancy at the end of the study. Of the 4,692 men who were administered the placebo, 5.1% were diagnosed with prostate cancer of considerable malignancy at the end of the study.

The reason for this small difference of 1.3% cannot be explained by the results of the study, but a number of possible explanations were put forward by the researchers:

• Androgen deprivation therapy (a therapy which diminishes the availability of androgens in tissues and organs and which may cause the changes in the tissue which imitate a greater degree of malignancy than actually present)
• Finasteride 5 mg may induce greater malignancy in prostate cancer by its action inside the prostate cells, or:
• Finasteride 5 mg appears to have preference for more malignant cancers rather than selectively inhibiting less malignant tumours.

The final conclusion, however, is that this result is still without a clear explanation and requires more investigation.

Advice for patients who are using or may use Finasteride

Finasteride 1 mg  

The results of the study cannot be generalized for patients who are taking a smaller dose (1 mg), which is the dosage used to treat hair loss. To repeat once more: only the 5 mg dose of finasteride was used in the study. This dosage is known to be effective in the benign enlargement of the prostate and was selected for the study for its known effects on the prostate tissue. Safety studies carried out on finasteride have never revealed any side effect of any significance which would limit its use to 1 mg for the treatment of hair loss. Those patients who have questions about the use of 1 mg finasteride should discuss them with their hair transplant specialist.

Finasteride 5 mg

Although the researchers studied the effect of 5 mg finasteride in the development of prostate cancer, the drug is generally not prescribed for this purpose. It is approved for the treatment of benign prostate hypertrophy and the associated symptoms, and the majority of men who use the drug are taking it for this purpose. The study showed that finasteride 5 mg can have an added benefit in preventing or retarding the appearance of prostate cancer of a high degree of malignancy, but could also be associated with a slight increase in the risk of developing this cancer. The reason for this small increase in the risk of prostate cancer of a high degree of malignancy was not explained by the results of the study.

The researchers recommend:

“With all of the information about the results of the treatment of prostate cancer published, patients (coordinating with their doctors) should balance the risks and benefits when it comes to deciding what’s best in terms of their own priorities with respect to the prevention of prostate cancer, urinal and sexual function, to reach a personal but informed decision on the use of finasteride” (Extract from the NEJM – see references).

References

Thompson IM, Goodman PJ, Tangen CM et al. The influence of finasteride in the development of prostate cancer. N Engl J Med 2003; 349:215 224. Scardino PT. The prevention of prostate cancer – the dilemma [editorial]. N Engl J Med 2003; 349:297-299. National Cancer Institute. Protocol for the prevention of Prostate Cancer.http:www.cancer.gov/clinical / view Brett AS. Comment. Journal Watch, 7/18/03.