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Low-Dose Lisinopril in Normotensive Men With Idiopathic Oligospermia and Infertility: A 5-Year Randomized, Controlled, Crossover Pilot Study



The outcomes of drug treatment for male infertility remain conjectural, with controversial study results. Our pilot study
employed a randomized, placebo-controlled, crossover methodology with intention-to-treat analysis. Thirty-three men
with idiopathic oligospermia were randomized to start either daily oral lisinopril 2.5 mg (n = 17) or daily oral placebo (n =
16). Lisinopril was found to cause a normalization of seminal parameters in 53.6% of the participants. Although the mean
ejaculate volume was unchanged (P ≥ 0.093), the total sperm cell count and the percentage of motile sperm cells increased
(P ≤ 0.03 and P < 0.001, respectively), whereas the percentage of sperm cells with abnormal morphology decreased (P ≤
0.04). The pregnancy rate was 48.5%, and there was no serious adverse drug event. It is concluded, albeit cautiously,
that prolonged treatment with 2.5 mg/day of oral lisinopril may be well tolerated in normotensive men with idiopathic
oligospermia, may improve sperm quantity and quality, and may enhance fertility in approximately half of those treated.