Are proton-pump inhibitors harmful for the semen quality of men in couples who are planning pregnancy?

Long-term proton-pump inhibitors use harms semen quality in men from couples planning pregnancy, suggesting that a long-term increase in gastric pH results in a decline of sperm quality.

Volume 106, Issue 7, Pages 1666-1672


Nicole A. Huijgen, M.D., Maria A.J. de Ridder, Ph.D., Katia M. Verhamme, Ph.D., Gert R. Dohle, Ph.D., Ann M. Vanrolleghem, M.Sc., Miriam C.J.M. Sturkenboom, Ph.D., Joop S.E. Laven, Ph.D., Régine P.M. Steegers-Theunissen, M.D., Ph.D.



To determine associations between proton-pump inhibitor (PPI) use and semen parameters in young men of couples who are planning pregnancy.


Case-control study of a population-based registry.


Not applicable.


General practitioner patients comprising 2,473 men from couples planning pregnancy with a recorded semen analysis: 241 with a low total motile sperm count (TMSC ≤1) and 714 with TMSC >1 as matched controls.



Main Outcome Measure(s)

Exposure to PPI; PPI dosage.


The study of data from between 1996 and 2013 from the Integrated Primary Care Information database in the Netherlands, which incorporates the medical records of 1.5 million patients from 720 general practitioners, found that the use of PPIs in the period between 12 and 6 months before semen analysis was associated with a threefold higher risk of low TMSC (odds ratio 2.96; 95% confidence interval 1.26–6.97) adjusted for age and other medication. Use of PPIs during the 6 months immediately before the semen analysis was not statistically significantly associated with low TMSC.


The use of PPIs in the period 12 to 6 months preceding semen analysis is associated with a threefold higher risk of low TMSC, which suggests that a long-term increase in gastric pH results in a decline of sperm quality. This finding emphasizes the need for more preconceptional research and counseling on the potential effects of medication use on semen quality.

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Go to the profile of Mary Samplaski
over 5 years ago
I would be interested to know if the controls were age matched. It does not make sense that a change in gastric pH would alter semen parameters. However, older men have a decline in semen quality, and are also more likely to take PPIs; I wonder if this is the true association.