Finasteride [5ARI] Induced/Associated Effects

[davesavvy]

Gur S, Kadowitz PJ, Hellstrom WJ. Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation. Expert Opin Drug Saf. An Error Occurred Setting Your User Cookie

Introduction: Treatment with 5-alpha reductase inhibitors (5ARI) is commonly utilized for the treatment of benign prostatic hyperplasia (BPH). The true prevalence of sexual side effects with 5ARI treatment is currently unknown.

Areas covered: The current article reviews the reported adverse effects of 5ARI in regard to erectile function, sexual desire and ejaculation. A PubMed search was performed of all articles from 1990 to present, which reported any sexual side effects with finasteride or dutasteride. Preference was given to more recent and human studies where available.

Expert opinion: Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5 - 9%. Decreased circulating dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARI. Patients receiving therapy with 5ARI should be counseled as to potential sexual and psychological adverse effects. Future clinical studies are needed to further investigate the sexual side effects associated with this class of drugs.

Accutane (isotretinoin) does the same thing. Google "accutane sexual dysfunction" and you'll see. Unfortunately I'm living proof. FDA is a f%$king joke.
https://www.google.com/search?client=ubuntu&channel=fs&q=isotretinoin+sexual+dysfunction&ie=utf-8&oe=utf-8#hl=en&safe=off&client=ubuntu&hs=Jk4&tbo=d&channel=fs&sclient=psy-ab&q=accutane+sexual+dysfunction&oq=accutane+sexual+dysfunction&gs_l=serp.3..0j0i22l3.60877.65618.1.67124.20.13.0.0.0.3.213.1387.5j7j1.13.0.les%3Bepmergenn..0.0...1.1.1Bdg0n8UoiI&psj=1&bav=on.2,or.r_gc.r_pw.r_cp.r_qf.&fp=54961953d5425771&bpcl=39580677&biw=1680&bih=932

 

[Dr JIM]

The assertion testosterone auto-antibodies (which are very rare) are the causative mechanism of SD (from 5aRIs) rather than the alteration of other steroidal hormones, depressed DHT levels in particular, is certainly NOT evidence based.

 

[OldGrower]

I wish the guy posting for an accutane source read this thread!

 

[Dr JIM]

Agreed OG there's a darn good reason the sole indication remains "SEVERE RECALCITRANT (to systemic antibiotics) CYSTIC (scarring) ACNE" and the FDA started a Accutane "data bank" many years back. The adverse effects may be PROFOUND!

 

[Drea'An]

I'm rather late in posting here, it's been a while. I was prescribed that drug at .5mg.
Something told me not to take it and I'm glad I did not. The drug was prescribe for my enlarge prostate gland which I find funny because with the doses of steroids I've been taking over the years, my prostate gland has shrunk to normal size and my PSA is almost at 1 ng/dl. Great stuff Test E and Super Test. It really boils down to the fact that some guys can benefit from the drug and some guys can not.
When I read the stories about guys that had lost it all, I was sadden and felt for them If only they had a angel a computer. I use olive oil and a oatmeal rub to aide with my acne problem.

 

[Michael Scally MD]

Ricci G, Martinelli M, Luppi S, et al. Finasteride and fertility: case report and review of the literature. J Drugs Dermatol 2012;11(12):1511-3. Finasteride and Fertility: Case Report and Review of the Literature: Scientific, Peer-Reviewed Dermatology Article Indexed with MEDLINE/PubMed

Although millions of men have taken or are taking finasteride, there are no documented cases of successful pregnancy in the literature after discontinuation of the drug. Early studies did not show significant influence of finasteride on semen parameters, whereas some recent observations have suggested that in subfertile patients, the effects of the drug might be amplified. Therefore, counseling is particularly difficult for men taking finasteride and planning pregnancy. We report the case of a couple whose male partner had used finasteride for approximately 10 years and who presented for primary infertility. The first semen analysis, carried out 3 months after finasteride cessation, revealed severe oligospermia. One month later, sperm concentration increased, and the following month, the couple spontaneously conceived. A healthy baby was delivered at full term. To the best of our knowledge, this is the first case of successful full-term pregnancy and live birth after long-term use of finasteride, which suggests that treatment with finasteride, even after several years, does not prevent normal conception. However, caution should be advised with the use of finasteride in male partners of couples who are attempting to become pregnant.

 

[Michael Scally MD]

Pugnaghi M, Monti G, Biagini G, Meletti S. Temporal lobe epilepsy exacerbation during pharmacological inhibition of endogenous neurosteroid synthesis. BMJ Case Rep 2013. http://casereports.bmj.com/content/2013/bcr-2012-008204.abstract

We report the case of a woman who presented cryptogenic temporal lobe seizures from the age of 43 years. Antiepileptic drug (AED) treatment with carbamazepine was able to control seizures for 1 year, but seizures relapsed and an add-on treatment with lamotrigine was started without achieving seizures control. The patient's medical history was unremarkable except for a mild hirsutism for which she was taking finasteride since 45 years of age. In view of the possible relationship between finasteride, a known inhibitor of neurosteroids synthesis, and patient's seizures exacerbation, we stopped finasteride resulting in prompt recovery of seizures control. It is know that 5alpha-dihydrosteroids are precursors of powerful positive modulators of gamma-aminobutyric acid-A inhibitory currents and exert antiseizure effects in animal epilepsy models. This case supports the hypothesis that endogenous neurosteroids can modulate seizure susceptibility and response to AEDs also in humans, suggesting their possible use as a new therapeutic option.

 

[Michael Scally MD]

Finasteride: No Prostate Cancer Survival Benefit

Background: As finasteride could reduce by 25% the number of prostate cancers (PCa) diagnosed in the U.S. annually, the public health benefit of prostate cancer prevention could be enormous. We performed a survival analysis to assess for any evidence of increased risk of death in men randomized to finasteride, a potential indicator of a ‘true’ increased risk of high grade (HG) disease in the PCPT.

Methods: A Social Security Death Index search was conducted on all randomized men to ascertain date of death. Cox proportional hazards models adjusting for known risk factors for overall survival and survival from time of diagnosis of PCa overall, low grade (LG) and HG were used to estimate hazard ratios (HR) and construct 95% confidence intervals to determine if survival on finasteride and placebo were equivalent.

Results: A total of 5,128 deaths have been reported; 2,584 men on finasteride and 2544 on placebo. 15-year survival rates for all randomized men in each arm is 78%. The HR for overall survival on finasteride compared to placebo is 1.04 (95% CI 0.96, 1.10, p=.19). 10-year survival from diagnosis for men with PCa was slightly higher for men randomized to finasteride (10-year survival 83% vs. 81%) but not statistically significant (HR= 0.87, 95% CI 0.73 - 1.04, p=.14). For the men with HG PCa, there was no evidence of worse survival on finasteride (HR= 1.01; 95% CI 0.73, 1.14, p=.97) while those diagnosed with LG disease finasteride had superior survival (HR= 0.73; 95% CI 0.57, 0.94, p=.01).

Conclusions: For men in PCPT with PCa there was no difference in survival from diagnosis date, a slightly-superior 10-year survival with finasteride and a statistically-superior survival among men with LG tumors in the finasteride group. A potential explanation for this phenomenon could be a lead-time bias. Arguing against this bias is the identical survival of HG PCa in both groups. Another potential explanation is that the men with LG PCa on placebo include a greater number with undetected HG disease; HG tumors in men on finasteride were more likely detected due to the improved performance of prostate biopsy. With follow-up of 18 years, finasteride administration for 7-years does not appear to affect mortality but significantly reduces the risk of a PCa diagnosis.

Goodman PJ, Thompson IM, Tangen CM, et al. Long-term survival of subjects in the prostate cancer prevention trial. Program and abstracts of the 2013 Genitourinary Cancers Symposium; February 14-16, 2013; Orlando, Florida. Abstract 10. https://meetinglibrary.asco.org/print/597781

 

[Michael Scally MD]

Inhibition of 5?-reductase type 1 with dutasteride impairs insulin sensitivity
Inhibition of 5

5?-Reductase (5?R) inhibitors decrease prostatic dihydrotestosterone in benign prostatic hyperplasia (BPH) treatment; finasteride inhibits 5?R type 2, while dutasteride inhibits 5?R1 and 2. 5?Rs, especially 5?R1, are also expressed in metabolic tissues regulating actions of androgens and other substrates, including glucocorticoids.

Hypothesis: 5?R1 inhibition with dutasteride induces metabolic dyshomeostasis.

Study: With ethical approval, in a double-blind RCT, we studied metabolism in 47 men (20–85 years) before and after 3 months of either dutasteride (0.5 mg daily; n= 17; D), finasteride (5 mg daily; n= 16; F) or control (tamsulosin; 0.4 mg daily; n= 14). The primary outcome was insulin sensitivity, measured during a two-step (10; 40 mU/m2 per min) hyperinsulinaemic euglycaemic clamp, with d2-glucose and d5-glycerol tracers. Data are mean (95% CI; P value) difference in change from baseline, compared by one-way ANOVA with LSD post-hoc tests where appropriate.

Results: D, but not F, impaired insulin sensitivity. During high-dose insulin, the M value (mean steady state glucose infusion rate) decreased with D vs both control and F, by 10.1 mg/kg fat-free mass/min (?16.3; ?3.9; P=0.002); signifying impaired skeletal muscle insulin sensitivity. Glucose and glycerol rates of appearance during low-dose insulin were unchanged. Tracer infusion alone induced hyperinsulinaemia only with D by 11 pmol/l (3; 20; P=0.009). D increased HOMA-IR and fasting C-peptide by 15% (3; 27; P=0.015), and 114.5 pmol/l (31.5; 197.6; P=0.007) respectively. Fasting glucose, cholesterol, body mass index, waist:hip ratio and blood pressure were unaltered. Body fat (bioimpedance) increased 2.6% (0.9; 4.2; P=0.003) with D. Post-treatment visceral and subcutaneous adipose volumes (magnetic resonance imaging; L4/5), and hepatic fat (1H spectroscopy), were unchanged. Serum adiponectin, resistin, IL8, and MCP1 were unchanged, however leptin increased 44% (16; 73; P=0.03) with D. In all indices F was not different to control.

Conclusion: 5?R inhibition with dutasteride, but not finasteride, impairs peripheral (principally muscle) insulin sensitivity, and increases body fat and leptin. 5?R1 inhibition is potentially detrimental to metabolic health; this may have important implications for BPH treatment.

 

[Michael Scally MD]

Corona G, Rastrelli G, Maseroli E, et al. Inhibitors of 5alpha-reductase-related side effects in patients seeking medical care for sexual dysfunction. J Endocrinol Invest 2013;35(10):915-20. Journal of Endocrinological Investigation

BACKGROUND: Despite their efficacy in the treatment of benign prostatic hyperplasia (BPH) the popularity of inhibitors of 5alpha-reductase (5ARI) is limited by their association with adverse sexual side effects. However, the real impact of 5ARI on sex hormones and sexual function is controversial.

AIM: To investigate the role of 5ARI therapy on hormonal parameters and sexual function in men already complaining of sexual problems.

MATERIALS AND METHODS: A consecutive series of 3837 men (mean age 63.5+/-12.8 yr) attending our outpatient clinic for sexual dysfunction was retrospectively studied. Several clinical, biochemical, and instrumental (penile color doppler ultrasound) factors were evaluated.

RESULTS: Among the patients studied, 78.7% reported erectile dysfunction, 51.1% hypoactive sexual desire (HSD), 86.7% perceived reduced sleep-related erections (PR-SRE) and 19.1% premature ejaculation. The use of 5ARI was associated with an increased risk of HSD and PR-SR whereas no relationship was found with erectile dysfunction and ejaculation disturbances. Subjects using 5ARI also more frequently had gynecomastia along with reduced SHBG and higher calculated free testosterone levels. All these associations were confirmed in a case-control study comparing 5ARI users with age-body mass index-smoking status and total testosterone-matched controls.

CONCLUSIONS: Our data indicates that use of 5ARI in men with sexual dysfunction does not significantly exacerbate pre-existing ejaculatory or erectile difficulties, but can further impair their sexual life by reducing sexual drive and spontaneous erection.

 

[Michael Scally MD]

Chhipa RR, Halim D, Cheng J, et al. The direct inhibitory effect of dutasteride or finasteride on androgen receptor activity is cell line specific. Prostate. The direct inhibitory effect of dutasteride or finasteride on androgen receptor activity is cell line specific - Chhipa - 2013 - The Prostate - Wiley Online Library

BACKGROUND: Finasteride and dutasteride were developed originally as 5alpha-reductase inhibitors to block the conversion of testosterone to dihydrotestosterone (DHT). These drugs may possess off-target effects on the androgen receptor (AR) due to their structural similarity to DHT.

METHODS: A total of four human prostate cancer cell models were examined: LNCaP (T877A mutant AR), 22Rv1 (H874Y mutant AR), LAPC4 (wild-type AR), and VCaP (wild-type AR). Cells were cultured in 10% charcoal-stripped fetal bovine serum, either with or without DHT added to the medium. AR activity was evaluated using the ARE-luciferase assay or the expression of AR regulated genes.

RESULTS: Dutasteride was more potent than finasteride in interfering with DHT-stimulated AR signaling. Disruption of AR function was accompanied by decreased cell growth. Cells that rely on DHT for protection against death were particularly vulnerable to dutasteride. Different prostate cancer cell models exhibited different sensitivities to dutasteride and finasteride. LNCaP was most sensitive, LAPC4 and VCaP were intermediate, while 22Rv1 was least sensitive. Regardless of the AR genotype, if AR was transfected into drug-sensitive cells, AR was inhibited by drug treatment; and if AR was transfected into drug-resistant cells, AR was not inhibited.

CONCLUSIONS: The direct inhibitory effect of dutasteride or finasteride on AR signaling is cell line specific. Mutations in the ligand binding domain of AR do not appear to play a significant role in influencing the AR antagonistic effect of these drugs. Subcellular constituent is an important factor in determining the drug effect on AR function.

 

[Michael Scally MD]

Wu Y, Godoy A, Azzouni F, Wilton JH, Ip C, Mohler JL. Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5alpha-reductase inhibitors. Prostate. Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5[]-reductase inhibitors - Wu - 2013 - The Prostate - Wiley Online Library

BACKGROUND: Blocking 5alpha-reductase-mediated testosterone conversion to dihydrotestosterone (DHT) with finasteride or dutasteride is the driving hypothesis behind two prostate cancer prevention trials. Factors affecting intracellular androgen levels and the androgen receptor (AR) signaling axis need to be examined systematically in order to fully understand the outcome of interventions using these drugs.

METHODS: The expression of three 5alpha-reductase isozymes, as determined by immunohistochemistry and qRT-PCR, was studied in five human prostate cancer cell lines. Intracellular testosterone and DHT were analyzed using mass spectrometry. A luciferase reporter assay and AR-regulated genes were used to evaluate the modulation of AR activity.

RESULTS: Prostate cancer cells were capable of accumulating testosterone to a level 15-50 times higher than that in the medium. The profile and expression of 5alpha-reductase isozymes did not predict the capacity to convert testosterone to DHT. Finasteride and dutasteride were able to depress testosterone uptake in addition to lowering intracellular DHT. The inhibition of AR activity following drug treatment often exceeded the expected response due to reduced availability of DHT. The ability to maintain high intracellular testosterone might compensate for the shortage of DHT.

CONCLUSIONS: The biological effect of finasteride or dutasteride appears to be complex and may depend on the interplay of several factors, which include testosterone turnover, enzymology of DHT production, ability to use testosterone and DHT interchangeably, and propensity of cells for off-target AR inhibitory effect.

 

[ViaSwiss]

Dr Scally can you interpret what those last 2 studies you posted are saying?

 

[Michael Scally MD]

Dr Scally can you interpret what those last 2 studies you posted are saying?

In a nutshell, almost all think that 5ARi (Finasteride & Dutasteride) act primarily by inhibiting DHT synthesis. What both of these studies are saying is the 5ARi are acting directly at the AR (and additional points)!

 

[ViaSwiss]

Thanks Dr Scally. I actually suffer from PFS, but I took Saw Palmetto. Previously I had known that SP does act on the Androgen Receptor (proof below), but this is the first research I have seen that shows Finasteride does as well. Pretty important link....Only question is....are the ARs still blocked or are they just de-sensitized (if either at all)?

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Other studies have shown that Serenoa extract inhibits androgenic activity by competing with DHT for the androgen receptor, thereby affecting testosterone metabolism.13 The binding of two synthetic androgens, mibolerone and methyltrienolone, that are specific for androgen receptors at low concentrations (5nM), were inhibited by Serenoa extract (Permixon) in a competitive manner. Various plant steroids were tested for competitive binding to androgen receptors and found to be inactive.13,14 The inhibitory effect of Serenoa extract on DHT and testosterone binding was tested in tissue from 11 BPH patients. An average of 40%-42% reduction in receptor binding was observed for both hormones.15

http://legacy.uspharmacist.com/oldforma ... icle_id=87
El-Sheikh MM. et al. The effect of Permixon on androgen receptors. Acta Obstet. Gynecol. Scand 1988;67:397-399


The bioactive substances in saw palmetto may actually interfere with the function of testosterone by blocking the androgenic and anabolic receptor sites of cells that testosterone needs to bind with to turn on cellular protein synthesis.

Saw Palmetto may actually interfere
with the function of testosterone.

Tests using tissue samples revealed that substances in saw palmetto actually reduced the tissue uptake of testosterone and dihydrotestosterone, which means saw palmetto bioactives blocked these anabolic hormones from entering cells, which is very anti-anabolic.

Bodybuilding.com - Avoiding The Anti-Anabolics For Maximum Muscle Growth!

 

[VICREP]

Hey guys I'm 22 and losing a bit of hair. MPB is strong in my family.

I'm thinking of starting fin but I constantly toss it up from all the reports of forums like this.

My question is do you believe it can be taken safely and effectively? I have read success stories of people using it long term with no side effects

Would running armidex alongside fin be worthwhile?

 

[Michael Scally MD]

Zhang MG, Wang XJ, Shen ZJ, Gao PJ. Long-term Oral Administration of 5alpha-reductase Inhibitor Attenuates Erectile Function by Inhibiting Autophagy and Promoting Apoptosis of Smooth Muscle Cells in Corpus Cavernosum of Aged Rats. Urology. Long-term Oral Administration of 5?-reductase Inhibitor Attenuates Erectile Function by Inhibiting Autophagy and Promoting Apoptosis of Smooth Muscle Cells in Corpus Cavernosum of Aged Rats

OBJECTIVE: To investigate the effects and mechanisms of long-term treatment of 5alpha-reductase inhibitors (5ARIs) on erectile organ structure and function in aged rats.

MATERIALS AND METHODS: Thirty 16-month-old male rats were assigned to 2 groups: untreated or treated with 5ARIs. After 16 weeks, the erectile function was measured after electrical stimulation of the cavernous nerve. The weights and histopathologic features of the corpus cavernosum were examined. The levels of autophagy, apoptosis, and protein expression were also recorded.

RESULTS: In the 5ARI-treatment group, the plasma and intraprostatic dihydrotestosterone concentration was lowered by 52.1% and 57.3%, respectively, and the weight of the corpus cavernosum and prostate had decreased by 22.4% and 35.6%, respectively. The in vivo erectile response to electrical stimulation of the cavernous nerve had decreased significantly in the 5ARI-treatment group (P <.001). Masson's staining, immunohistochemistry, and Western blot all demonstrated decreased smooth muscle and increased collagen deposition and decreased endothelial nitric oxide synthase and LC3-II protein expression in the corpus cavernosum of the 5ARI-treatment group. Using transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, decreased autophagy, aggravated ultrastructural injury of mitochondria, and increased apoptosis were observed in the cavernous smooth muscle cells from the rats in the 5ARI-treatment group.

CONCLUSION: Long-term 5ARI treatment did attenuate the erectile function of aged rats. The mechanisms might have been the decreased rate of autophagy and an increased rate of apoptosis in the cavernous smooth muscle cells, suggesting a new role for androgen in maintaining the structural and functional integrity of the erectile organ. Additional studies are necessary to demonstrate the mechanisms of dihydrotestosterone in regulating the autophagy and apoptosis of the cavernous smooth muscle cells.

 

[Michael Scally MD]

Melcangi RC, Caruso D, Abbiati F, et al. Neuroactive Steroid Levels are Modified in Cerebrospinal Fluid and Plasma of Post-Finasteride Patients Showing Persistent Sexual Side Effects and Anxious/Depressive Symptomatology. The Journal of Sexual Medicine. Neuroactive Steroid Levels are Modified in Cerebrospinal Fluid and Plasma of Post-Finasteride Patients Showing Persistent Sexual Side Effects and Anxious/Depressive Symptomatology - Melcangi - 2013 - The Journal of Sexual Medicine - Wiley Online Libr

Introduction Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5?-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation.

Aim A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology.

Methods The levels of neuroactive steroids were evaluated by liquid chromatography–tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls.

Main Outcome Measures Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls.

Results At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17?-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5?-androstane-3?,17?-diol and 17?-estradiol were observed in plasma.

Conclusion The present observations confirm that an impairment of neuroactive steroid levels, associated with depression symptoms, is still present in androgenic alopecia patients treated with finasteride despite the discontinuation of the treatment.

 

[ViaSwiss]

Curious as to why they do not suspect that low nuerosteroids can cause ED and low libido? Not activating GABA-a (bodies main stress defense mechanism) would most def. lower ones libido.

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Study Aims to Identify Causes at Molecular Level of Condition Potentially Affecting Thousands of Men Worldwide.


http://www.pfsfoundation.org/news/clinical-study-of-post-finasteride-syndrome-launched-at-brigham-and-womens-hospital-a-harvard-medical-school-teaching-affiliate/

 

[Michael Scally MD]

Re: Prostate Cancer

What can we now conclude about the use of finasteride for prevention? The safest conclusion is that it has no short- or long-term effect on all-cause mortality, so we cannot recommend its use to prolong life. For men who choose regular prostate-cancer screening, the use of finasteride meaningfully reduces the risk of prostate cancer and thus the morbidity associated with treatment of the disease. Whether the use of the drug has either a positive or a negative effect on prostate-cancer–specific mortality remains unknown, but either way the effect is probably very small and does not result in any difference in life expectancy.

Thompson IM, Goodman PJ, Tangen CM, et al. Long-Term Survival of Participants in the Prostate Cancer Prevention Trial. New England Journal of Medicine 2013;369(7):603-10. MMS: Error

BACKGROUND - In the Prostate Cancer Prevention Trial (PCPT), finasteride significantly reduced the risk of prostate cancer but was associated with an increased risk of high-grade disease. With up to 18 years of follow-up, we analyzed rates of survival among all study participants and among those with prostate cancer.

METHODS - We collected data on the incidence of prostate cancer among PCPT participants for an additional year after our first report was published in 2003 and searched the Social Security Death Index to assess survival status through October 31, 2011.

RESULTS - Among 18,880 eligible men who underwent randomization, prostate cancer was diagnosed in 989 of 9423 (10.5%) in the finasteride group and 1412 of 9457 (14.9%) in the placebo group (relative risk in the finasteride group, 0.70; 95% confidence interval [CI], 0.65 to 0.76; P<0.001). Of the men who were evaluated, 333 (3.5%) in the finasteride group and 286 (3.0%) in the placebo group had high-grade cancer (Gleason score, 7 to 10) (relative risk, 1.17; 95% CI, 1.00 to 1.37; P=0.05). Of the men who died, 2538 were in the finasteride group and 2496 were in the placebo group, for 15-year survival rates of 78.0% and 78.2%, respectively. The unadjusted hazard ratio for death in the finasteride group was 1.02 (95% CI, 0.97 to 1.08; P=0.46). Ten-year survival rates were 83.0% in the finasteride group and 80.9% in the placebo group for men with low-grade prostate cancer and 73.0% and 73.6%, respectively, for those with high-grade prostate cancer.

CONCLUSIONS - Finasteride reduced the risk of prostate cancer by about one third. High-grade prostate cancer was more common in the finasteride group than in the placebo group, but after 18 years of follow-up, there was no significant between-group difference in the rates of overall survival or survival after the diagnosis of prostate cancer. (Funded by the National Cancer Institute.)