Finasteride Update 2015

POINT/COUNTERPOINT – International Society of Hair Restoration Surgery (ISHRS) Task Force on Finasteride Adverse Events 2015

At the ISHRS annual scientific meeting in Chicago, there was an excellent update on finasteride side effects by guest speaker and specialist in male infertility and sexual medicine, Dr. Mohit Khera, Associate Professor in the Department of Urology at Baylor College of Medicine.

Post Finasteride Syndrome (PFS)

Dr. Khera mentioned his conflict of interest in that his study was funded by a grant from the Post-Finasteride Foundation (PFF). This foundation was started by two physicians whose son developed severe depression while using finasteride. The organization’s mission is to increase global awareness of, “The often life-altering, devastating sexual, neurological, and physical side effects that persist in men who have taken the 5-alpha reductase type II enzyme inhibitor finasteride.”

While there are a number of clinician and research members of the International Society of Sexual Medicine and Sexual Medicine Society of North America who have strong opinions that PFS is a real entity, no studies to date have defined the at-risk patient population, the actual incidence, or the mechanism that could explain persistent symptoms. The often-quoted publications of Dr. Michael Irwig have been heavily criticized for using a patient database that was obtained from a website with strong bias influence of this group. Conclusions from his “studies,” which have extreme selection bias and lack scientific controls, should be regarded with skepticism.

Male Breast Tissue

Gynecomastia is a well-documented adverse event reported in up to 2% of men taking 5-ARIs. Dr Khera raised an alarm concerning male breast cancer quoting a study in which four out of 1,554 men taking finasteride developed breast cancer, 200 times the general population. In my review of finasteride and dutasteride double- blinded, controlled studies, of 28,000 men taking finasteride vs. placebo, eight cases of breast cancer were reported, three taking finasteride and five placebos. Of 22,400 men taking dutasteride vs. placebo, three cases of breast cancer, two with dutasteride and one placebo. Based on these two large cohort studies, there is no statistical evidence to arrive at the conclusion of an increased incidence of breast cancer in men using 5-ARIs. While the patient information packets for finasteride and dutasteride mention post marketing associations with breast cancer, 50 cases have been reported in the world’s literature, and 26 developed in less than a year within starting finasteride.

The Million Women Study in the United Kingdom was set up to investigate the effects of specific types of hormone replacement therapy on incident and fatal breast cancer. It concluded that the risk of breast cancer increased with increasing total duration of use. The report in men of so many cases within one year of starting the drug, suggests that the cancers were not induced by finasteride. These cancers were already present and detected due to early discovery. A review of this issue in the Journal of Urology in November 2013 concluded,” the lack of an association suggests that the development of breast cancer should not influence the prescribing of 5-ARI therapy.”

Infertility

During the Q&A session, Dr Khera recommended against using finasteride in couples attempting conception. While his expertise is in infertility, there is ample data to support the opposite opinion, that there is insufficient finasteride in normal ejaculate volume to adversely affect a potentially pregnant woman, or to reduce spermatogenesis or infertility in healthy men chronically taking finasteride. The few studies with small populations implicating a reduction in male fertility appear to be in subfertile men or those with an underlying condition such as varicocele.

Prostate Cancer

Attendees may have left with the impression that 5-ARIs cause high-grade prostate cancer. The original PCPT study found a higher percentage of high-grade prostate cancer in men taking finasteride; however, subsequent analysis found multiple counter arguments against this increase being a real risk. Analysis of this same cohort 18 years later showed no significant difference between the two groups in rates of overall survival or survival after diagnosis of prostate cancer. Based on this information, it can be concluded that the increased Gleason scores initially noted were due to better detection by biopsy in prostates that were smaller from the effects of finasteride and possibly increased sensitivity of PSA testing.

Placebo controlled clinical trials are needed to assess the incidence and possible etiology of CNS and sexual side effects, as well as determining which patient populations are at risk. The significant psychological aspects of potential side effects, magnified by sensationalized information on the internet and in the media, complicates the interpretation of data obtained outside of bilateral-controlled, blinded scientific studies.

References

• Beral V et al, Lancet. 2003 Aug 9;362(9382):419-27
• Bird et al, Journal of Urology 2013:190; 1811-14
• Overstreet, Fuh, Howards, Hellstrom et al Journal of Urology 1999:162 1295-1300
• Samplaski et al. Fertility and Sterility, Dec 2013