5-ARI may have adverse metabolic effects

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Authors of a recent study say that long-term therapy with a 5-alpha-reductase inhibitor was associated with increased glucose, increased glycated hemoglobin, and altered lipid profiles.

While the sexual side effects of finasteride (Proscar) and dutasteride (Avodart) are well known, a small but increasing body of research suggests that these agents potentially may have some metabolic effects in men who undergo long-term therapy.

Most of this evidence to date comes from basic science investigations, but the most recently published report pointing in this direction is a retrospective analysis of patient registry data. Authors of the new study say that long-term dutasteride therapy was associated with increased glucose, increased glycated hemoglobin (HbA_1c), and altered lipid profiles.

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“I think our study corroborates the clinical science, which is limited, but also the basic science, which is significant,” said first author Abdulmaged M. Traish, PhD, MBA, of Boston University School of Medicine, Boston.

While further study is warranted before any firm clinical conclusions can be drawn, Dr. Traish said he hoped urologists, endocrinologists, and others would at least take time to read the medical literature on the potential association, and share that with patients.

“Men with BPH may have to take these drugs for many years,” Dr. Traish said in an interview with Urology Times. “Clinicians should really discuss the potential benefit and potential risks with patients before starting therapy.”

The retrospective study, published online in Hormone Molecular Biology and Clinical Investigation (June 21, 2017), included a cohort of 230 men treated with dutasteride for lower urinary tract symptoms secondary to BPH, and another cohort of 230 men treated with tamsulosin (Flomax). The men were followed for 36-42 months.

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For the group of men treated with dutasteride, investigators noted a progressive increase in fasting blood glucose levels from baseline (6.77+/–0.55 mg/dL; p<.0001) along with an increase in HbA_1c (0.7+/–0.02%; p<.0001). By comparison, no such rises were seen in the cohort of men treated with tamsulosin.

Dutasteride also appeared to be associated with increases in aspartate transaminase and aminotransferase activity, while tamsulosin was not. This suggests inhibition of 5-alpha-reductase may bring about biochemical changes in liver function that may represent alterations in liver metabolism or increased inflammation, Dr. Traish and colleagues wrote.

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Other endpoints reported in the study included cholesterol measurements and sexual side effects:

Dutasteride treatment was associated with a significant increase in LDL cholesterol, but not HDL cholesterol levels, according to investigators.

The tamsulosin group also experienced an increase in LDL cholesterol, but in contrast to the dutasteride group, also had an increase in HDL cholesterol.

As expected based on previously published reports, dutasteride was also associated with reduced total testosterone plasma levels, increased score on the Aging Males' Symptoms (AMS) scale, and increased erectile dysfunction as compared with tamsulosin.

Limitations of the analysis, Dr. Traish acknowledged, include its retrospective nature, the lack of a control group, and some imbalances in patient characteristics. Notably, the tamsulosin group had a significantly larger mean waist circumference, higher body weight, and elevated LDL and HDL values compared with the dutasteride group. The tamsulosin group also had a lower mean AMS score at baseline.

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However, Dr. Traish said he hopes that these results will spark further interest from clinical collaborators who would like to undertake further research.

“By putting this paper out,” he said, “I’m trying to provoke myself, as well as my colleagues in the clinical and research community, to say, ‘let’s take a serious look at this.’ ”