Testosterone Plus Finasteride Improves BMD in Men With Low Testosterone

Laurie Barclay, MD

February 25, 2004

Feb. 25, 2004 — The combination of testosterone (T) and finasteride (F) improves bone mineral density (BMD) in men with low T levels without increasing prostate-specific antigen (PSA) levels, according to the results of a randomized trial published in the February issue of the Journal of Clinical Endocrinology & Metabolism. The editorialist warns that longer-term follow-up of PSA levels and of fracture risk is needed.

"Older men, particularly those with low serum T levels, might benefit from T therapy to improve BMD and reduce fracture risk. Concerns exist, however, about the impact of T therapy on the prostate in older men," write John K. Amory, from the University of Washington School of Medicine in Seattle, and colleagues. "We hypothesized that the combination of T and F, a 5α-reductase inhibitor, might increase BMD in older men without adverse effects on the prostate."

In a three-way randomization, 70 men aged 65 years or older, with serum T less than 12.1 nmol/L on two occasions, received T enanthate, 200 mg intramuscularly every two weeks with placebo pills daily (T-only); T enanthate, 200 mg every two weeks with 5 mg F daily (T+F); or placebo injections and pills (placebo). Low BMD was not a requirement for enrollment. Dual x-ray absorptiometry determined BMD of the lumbar spine and hip at baseline and serially.

Of the 70 men who entered the study, 50 completed the 36-month protocol. Intent-to-treat analysis including all men for as long as they provided data revealed that T therapy for 36 months increased BMD. At the lumbar spine, percentage increase in BMD from baseline was 10.2% ± 1.4% for T-only, 9.3% ± 1.4% for T+F, and 1.3% ± 1.4% for placebo ( P < .001 for T groups vs. placebo). At the hip, corresponding increases in BMD were 2.7% ± 0.7%, 2.2% ± 0.7%, and -0.2% ± 0.7%, respectively ( P <= .02). Both the intertrochanteric and trochanteric regions of the hip had significant increases in BMD.

Compared with baseline, the bone-resorption marker urinary deoxypyridinoline decreased significantly after six months of treatment in both the T-only and T+F groups ( P < .001). However, this marker was not significantly reduced in the T groups compared with the placebo group.

During the 36-month study, PSA levels increased from baseline in the T-only group ( P < .001). Although prostate volume increased in all groups, this increase was significantly less in the T+F group than in the T-only group or in the placebo group ( P = .02).

The authors conclude that T therapy in older men with low serum T increases vertebral and hip BMD during 36 months of treatment, either when given alone or in combination with F, suggesting that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men.

"In addition, the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy," they write. "These findings have important implications for the prevention and treatment of osteoporosis in older men with low T levels."

The National Institutes of Health supported this study.

In an accompanying editorial, Elizabeth Barrett-Connor, from the University of California at San Diego, and Shalender Bhasin, from the University of California in Los Angeles, refer to these results as "most impressive" but ask if they are clinically relevant. They note that 30% of the men in the T group required a dose reduction to manage a hematocrit increase of 52% or greater, raising concerns about the optimal dose.

"Just as improved bone density is insufficient to show fracture prevention, short trials showing modest PSA changes will be unsatisfactory to ensure prostate safety," they write. "It is important to get answers to these risk-benefit issues before we make assumptions based on biological plausibility and intermediate outcomes."

J Clin Endocrinol Metab. 2004;89:501-502, 503-510

Reviewed by Gary D. Vogin, MD