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

Abstract

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.

Seminal, ultrasound and psychobiological parameters correlate with metabolic syndrome in male members of infertile couples

“…In that study, (Muciaccia et al, 2012) the link between elevated blood pressure and abnormal morphology/DNA fragmentation was not clarified, but it was hypothesized that hypertension induces, within the testis, a generally altered vascular status characterized by enhanced ROS generation and limited antioxidant defence (Sharma et al, 1999;Brownlee, 2005;Amaral et al, 2008). Another recently published report (Mbah et al, 2012) indicates that treating normotensive, oligospermic men Table 4 Comparisons between subjects with metabolic syndrome (MetS) and 1 : 3 ratio matched controls (matched for age, body mass index, total testosterone, smoking habit, alcohol consumption, past or present cryptorchidism, leucocytospermia, current positive urine and/or semen cultures with a low-dose angiotensin converting enzyme inhibitor (lisinopril, 2.5 md/daily) ameliorates, in a rigorous placebo-controlled, crossover design, semen parameters, including sperm number, motility and morphology. In a rabbit model of MetS, also characterized by hypertension, we observed an increase in advanced glycation end products and their receptor (RAGE) in the seminiferous epithelium and in the cytoplasm of Sertoli cells, spermatocytes and spermatids respectively (Mallidis et al, 2011).…”

Angiotensin-Converting Enzymes Play a Dominant Role in Fertility

“…Despite the controversial study results, there are data supporting the use of ACEIs as effective drugs for the management of infertile men with idiopathic oligospermia, because of its beneficial effect on the sperm number, motility and morphology [18,98]. ACEIs exert beneficial effects on the sperm quantity and quality by blocking the conversion of bradykinin in the related kallikrein–kinin system into inactive peptides [99].…”

“…Furthermore, the ACE1 has become a promising target for the treatment of MetS, which increases the risk factors of infertility, such as obesity, IR and so on [15–17]. Some studies further pointed out that ACE1 inhibitors (ACEIs) have become first-line drugs for some fertile issues [18,19]. This review attempts to summarize and explore the relationship between the sterility and ACEs expression in the ovaries and testes.…”

An evidence‐based systematic review of the off‐label uses of lisinopril

“…Lisinopril was found to cause a normalization of seminal parameters in 53.6% of the participants. Although the mean ejaculate volume was unchanged, the total sperm cell count and the percentage of motile sperm cells increased, whereas the percentage of sperm cells with abnormal morphology decreased (Tables and ).…”

“…Therefore, lisinopril, by inhibiting angiotensin II formation, can reduce this fibrogenesis effect . ACE‐inhibitors can modulate the actions of sex hormones, cytokines, growth factors and leptins, thereby improving oligospermia and infertility . Studies show that ACE is produced locally by vascular endothelial cells, which may have direct detrimental effects on retinal flow and vascular structure (independent of changes in systemic blood pressure).…”