Low-dose lisinopril in normotensive men with idiopathic oligospermia and infertility: a 5-year randomized, controlled, crossover pilot study

Mbah AU; Ndukwu GO; Ghasi SI; Shu EN; Ozoemena FN; Mbah JO; Onodugo OD; Ejim EC; Eze MI; Nkwo PO; Okonkwo PO

doi:10.1038/clpt.2011.265

Male Fertility Male Factor Treatment

Low-dose lisinopril in normotensive men with idiopathic oligospermia and infertility: a 5-year randomized, controlled, crossover pilot study

Mbah AU, Ndukwu GO, Ghasi SI, Shu EN, Ozoemena FN, Mbah JO, Onodugo OD, Ejim EC, Eze MI, Nkwo PO, Okonkwo PO

Published April 2012 Clinical Pharmacology and Therapeutics, 91(4), 582-589

DOI 10.1038/clpt.2011.265 PMID 22378155

RRM Academy Synopsis

Low-dose lisinopril was linked to higher sperm counts in a pilot trial

Sperm count and the share of motile sperm rose during low-dose lisinopril treatment in a randomized, double-blind crossover pilot trial of 33 men with low sperm counts of unknown cause. Of the 28 men who finished, 15 improved overall, to varying degrees. About 5 out of 10 couples had an unassisted pregnancy during the study.

About 5 in 10 couples had an unassisted pregnancy during the study. Source: Mbah AU et al., 2012, PMID 22378155.

Study at a glance, randomized, double-blind crossover: Sperm count rose during low-dose lisinopril in a small pilot trial — Study at a glance, randomized, double-blind crossover of 33 men: Sperm count rose during low-dose lisinopril in a small pilot trial. Source: Mbah AU et al., 2012, PMID 22378155.

Key Findings

Sperm count rose in the lisinopril-onset group (P ≤ 0.03), fell after switching to placebo (P ≤ 0.02), and rose in the placebo-onset group after switching to lisinopril (P ≤ 0.004).
In the lisinopril-onset group, the percentage of motile sperm first rose at week 12 (P < 0.001) and the percentage with abnormal morphology fell from week 12 to 112 (P ≤ 0.04).
Among the 28 completers, 15 (53.6%) improved overall to varying degrees, 4 (14.3%) decreased in quantity and quality, and 6 (21.4%) decreased in quality with no significant change in quantity.
Unassisted pregnancy occurred in 16 families, a couple pregnancy rate of 48.5%, and the trial recorded 13 deliveries; none of the babies had an obvious anomaly.
Symptom distributions did not differ between treatments (P = 0.74); chest pain, dizziness and joint pain were significantly more common with lisinopril, and no event warranted hospitalization or withdrawal.

Interpretation

This randomized, double-blind crossover trial scheduled each man to take lisinopril and placebo in turn, switching at week 96. Sperm count followed the treatment in both groups, and the authors conclude that lisinopril is linked to the changes in sperm count. In the lisinopril-onset group, mean sperm count stayed above baseline at week 282 despite placebo from week 96 (P < 0.001). Participants were men aged 24 to 34 with normal blood pressure from one Nigerian fertility clinic, all taking their usual fertility medications. The authors note that their sample was small. The findings support larger studies of this approach.

RRM Context

In restorative reproductive medicine, oligospermia of unknown cause is an undiagnosed condition with a cause still to be found. The authors suggest it may be a group of conditions with different mechanisms, and link this to the varied responses among individual men. Their introduction puts male factor at about 50% of all infertility problems. Restorative reproductive medicine takes a couple-level view and evaluates both partners.

Our editorial summary of this paper, not the article's abstract.

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.

Topics

Male Fertility

Male Factor Treatment Medical Management

Male Fertility › Male Factor Treatment › Medical Management

PMID 22378155 22378155 DOI 10.1038/clpt.2011.265 10.1038/clpt.2011.265 Mbah et al. 2012, Mbah 2012

Keywords

Adult, Cross-Over Studies, Dose-Response Relationship, Drug, Female, Humans, Infertility, Male/drug Therapy/epidemiology, Lisinopril/administration & Dosage, Longitudinal Studies, Male, Oligospermia/drug Therapy/epidemiology, Pilot Projects, Pregnancy, Pregnancy Rate/trends, Sperm Count/methods, Young Adult, Lisinopril

Low-dose lisinopril in normotensive men with idiopathic oligospermia and infertility: a 5-year randomized, controlled, crossover pilot study

Low-dose lisinopril was linked to higher sperm counts in a pilot trial

Key Findings

Interpretation

RRM Context

Abstract

Topics

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Keywords