Effect of Denosumab on Sperm Concentration in Men With Severe Oligospermia: A Randomized Controlled Trial.

Abstract

RANKL has been suggested as a novel regulator of male reproduction, and a recent randomized controlled trial (RCT) showed that the RANKL-inhibitor denosumab, normally used to treat osteoporosis, can improve semen quality in infertile men with high anti-Müllerian hormone (AMH) and small testicles. Therefore, this RCT aimed to investigate the effect of denosumab in men with severe oligospermia prospectively selected by serum AMH and testicular size. A double-blinded, placebo-controlled, single-center RCT, including 42 men with oligospermia with the main endpoint of improving sperm concentration. The groups were randomized 2:1 to receive either a single subcutaneous injection of denosumab 60 mg (n = 28) or a placebo treatment (n = 14) for 80 days. Thirty-nine men completed the study, with 26 assigned to the denosumab group and 13 to the placebo group. No differences in sperm concentration or total sperm count were found at day 80 between those treated with denosumab or placebo. Additionally, there were no differences in serum testosterone, LH, FSH, inhibin B, or AMH. Men treated with denosumab or placebo experienced an increase in both sperm concentration and total sperm count but not serum inhibin B from baseline to day 80. This RCT showed that denosumab did not improve sperm concentration or alter reproductive hormones compared to placebo. Denosumab is not superior to the vitamin D- and calcium-supplemented men in the placebo group.