Top

Published in:

Open Access 01-03-2017 | Original Research Article

Effect of Medications for Gastric Acid-Related Symptoms on Total Motile Sperm Count and Concentration: A Case–Control Study in Men of Subfertile Couples from the Netherlands

Authors: Nicole A. Huijgen, Hedwig J. Goijen, John M. Twigt, Annemarie G. M. G. J. Mulders, Jan Lindemans, Gert R. Dohle, Joop S. E. Laven, Régine P. M. Steegers-Theunissen

Published in: Drug Safety | Issue 3/2017

Abstract

Introduction

Gastric acid-related symptoms are highly prevalent in the general population (21–40%), and more than 11% of individuals use medication for the treatment of these symptoms. The uptake of micronutrients is dependent on the gastrointestinal potential of hydrogen (pH).

Objective

We hypothesized that medication affecting gastrointestinal pH reduces the availability of B vitamins, thereby deranging one-carbon metabolism and detrimentally affecting spermatogenesis.

Methods

This explorative nested case–control study in men of subfertile couples investigated associations between medication used for gastric acid-related symptoms and semen parameters. We included 40 men using medication for gastric acid-related symptoms and 843 men not using medication. Semen analyses were performed between 70 days before and 21 days after the visit.

Results

The use of medication was associated with a twofold higher risk of a low total motile sperm count [TMSC <1 × 10⁶, odds ratio (OR) 2.090, p = 0.049] and negatively with sperm concentration (β −0.320, p = 0.028). Red blood cell folate was positively associated with TMSC (β 0.257, p = 0.026), sperm count (β 1.679, p = 0.013) and ejaculate volume (β 0.120, p = 0.023), and total homocysteine (tHcy) was negatively associated with sperm count (β −0.077, p = 0.021).

Conclusion

Here we delineate associations between the use of medication for gastric acid-related symptoms and poor semen quality in men of subfertile couples. The use of medication for gastric acid-related symptoms is associated with a twofold higher risk of a low TMSC and a decreased sperm concentration. Although these findings warrant further research on causality, the associations between folate, tHcy and semen quality emphasize the importance of preconception counselling in male subfertility.

Available only for authorised users

Evers JL. Female subfertility. Lancet. 2002;360(9327):151–9. doi:10.1016/S0140-6736(02)09417-5.CrossRefPubMed

van der Steeg JW, Steures P, Eijkemans MJ, Hompes PG, Kremer JA, et al. Role of semen analysis in subfertile couples. Fertil Steril. 2011;95(3):1013–9. doi:10.1016/j.fertnstert.2010.02.024.CrossRefPubMed

Tielemans MM, Jaspers Focks J, van Rossum LG, Eikendal T, Jansen JB, Laheij RJ, et al. Gastrointestinal symptoms are still prevalent and negatively impact health-related quality of life: a large cross-sectional population based study in The Netherlands. PLoS One. 2013;8(7):e69876. doi:10.1371/journal.pone.0069876.CrossRefPubMedPubMedCentral

Ronkainen J, Aro P, Storskrubb T, Johansson SE, Lind T, Bolling-Sternevald E, et al. Prevalence of Barrett’s esophagus in the general population: an endoscopic study. Gastroenterology. 2005;129(6):1825–31. doi:10.1053/j.gastro.2005.08.053.CrossRefPubMed

Laine L, Ahnen D, McClain C, Solcia E, Walsh JH. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther. 2000;14(6):651–68 (pii: apt768).CrossRefPubMed

Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435–42. doi:10.1001/jama.2013.280490.CrossRefPubMed

Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med. 1994;120(3):211–5.CrossRefPubMed

Steegers-Theunissen RP, Twigt J, Pestinger V, Sinclair KD. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum Reprod Update. 2013;19(6):640–55. doi:10.1093/humupd/dmt041.CrossRefPubMed

Boxmeer JC, Smit M, Utomo E, Romijn JC, Eijkemans MJ, Lindemans J, et al. Low folate in seminal plasma is associated with increased sperm DNA damage. Fertil Steril. 2009;92(2):548–56. doi:10.1016/j.fertnstert.2008.06.010.CrossRefPubMed

10.

Boxmeer JC, Smit M, Weber RF, Lindemans J, Romijn JC, Eijkemans MJ, et al. Seminal plasma cobalamin significantly correlates with sperm concentration in men undergoing IVF or ICSI procedures. J Androl. 2007;28(4):521–7. doi:10.2164/jandrol.106.001982.CrossRefPubMed

11.

Vujkovic M, de Vries JH, Dohle GR, Bonsel GJ, Lindemans J, Macklon NS, et al. Associations between dietary patterns and semen quality in men undergoing IVF/ICSI treatment. Hum Reprod. 2009;24(6):1304–12. doi:10.1093/humrep/dep024.CrossRefPubMed

12.

Wong WY, Thomas CM, Merkus JM, Zielhuis GA, Steegers-Theunissen RP. Male factor subfertility: possible causes and the impact of nutritional factors. Fertil Steril. 2000;73(3):435–42 (pii: S0015-0282(99)00551-8).CrossRefPubMed

13.

Ebisch IM, Pierik FH, de Jong FH, Thomas CM, Steegers-Theunissen RP. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int J Androl. 2006;29(2):339–45. doi:10.1111/j.1365-2605.2005.00598.x.CrossRefPubMed

14.

Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002;77(3):491–8 (pii: S0015028201032290).CrossRefPubMed

15.

World Health Organization DoRHaR. WHO laboratory manual for the examination and processing of human semen. Geneva: World Health Organization; 2010.

16.

World Health Organization DoRHaR. WHO laboratory manual for the examination of human semen and sperm–cervical mucus interaction. 4th ed. Cambridge: World Health Organization; 1999.

17.

Beijer C, Kooij van R, Repping S, Rhemrev JP, Breejen EME. Multidisciplinaire richtlijn Semenanalyse: Nederlandse Vereniging voor Obstetrie en Gynaecologie; 2011 [in Ducth, updated 2011; cited 2012 9 november]. Available from: http://nvog-documenten.nl/uploaded/docs/Multidisciplinaire%20richtlijn%20Semenanalyse%20def.pdf

18.

Repping S, van Weert JM, Mol BW, de Vries JW, van der Veen F. Use of the total motile sperm count to predict total fertilization failure in in vitro fertilization. Fertil Steril. 2002;78(1):22–8 (pii: S0015028202031783).CrossRefPubMed

19.

Rhemrev JP, Lens JW, McDonnell J, Schoemaker J, Vermeiden JP. The postwash total progressively motile sperm cell count is a reliable predictor of total fertilization failure during in vitro fertilization treatment. Fertil Steril. 2001;76(5):884–91 (pii: S0015-0282(01)02826-6).CrossRefPubMed

20.

Brouwer IA, van Dusseldorp M, Thomas CM, Duran M, Hautvast JG, Eskes TK, et al. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr. 1999;69(1):99–104.PubMed

21.

Eisenberg ML, Li S, Behr B, Pera RR, Cullen MR. Relationship between semen production and medical comorbidity. Fertil Steril. 2015;103(1):66–71. doi:10.1016/j.fertnstert.2014.10.017.CrossRefPubMed

22.

Sanchez-Pozo MC, Mendiola J, Serrano M, Mozas J, Bjorndahl L, Menkveld R, et al. Proposal of guidelines for the appraisal of SEMen QUAlity studies (SEMQUA). Hum Reprod. 2013;28(1):10–21. doi:10.1093/humrep/des355.CrossRefPubMed

23.

Magnusdottir EV, Thorsteinsson T, Thorsteinsdottir S, Heimisdottir M, Olafsdottir K. Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Hum Reprod. 2005;20(1):208–15. doi:10.1093/humrep/deh569.CrossRefPubMed

24.

Hayashi T, Miyata A, Yamada T. The impact of commonly prescribed drugs on male fertility. Hum Fertil (Camb). 2008;11(3):191–6. doi:10.1080/14647270701739566.CrossRefPubMed

25.

Gupta A, Gupta S, Tiwary AK. Spermicidal efficacy of H2-receptor antagonists and potentiation with 2’, 4’-dichlorobenzamil hydrochloride: role of intrasperm Ca2+. Contraception. 2003;68(1):61–4 (pii: S0010782403001021).CrossRefPubMed

26.

Van Thiel DH, Gavaler JS, Smith WI Jr, Paul G. Hypothalamic–pituitary–gonadal dysfunction in men using cimetidine. N Engl J Med. 1979;300(18):1012–5. doi:10.1056/NEJM197905033001803.CrossRefPubMed

27.

Wang C, Wong KL, Lam KC, Lai CL. Ranitidine does not affect gonadal function in man. Br J Clin Pharmacol. 1983;16(4):430–2.CrossRefPubMedPubMedCentral

28.

Huijgen N, De Ridder M, Verhamme K, Dohle GR, Vanrolleghem A, Sturkenboom MC et al. Are proton-pump inhibitors harmful for semen quality in men of couples planning pregnancy? Fertil Steril. 2016;0015-0282. doi:10.1016/j.fertnstert.2016.09.010.

29.

Hammiche F, Laven JS, Twigt JM, Boellaard WP, Steegers EA, Steegers-Theunissen RP. Body mass index and central adiposity are associated with sperm quality in men of subfertile couples. Hum Reprod. 2012;27(8):2365–72. doi:10.1093/humrep/des177.CrossRefPubMed

30.

Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Buck Louis GM. The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Hum Reprod. 2014;29(2):193–200. doi:10.1093/humrep/det428.CrossRefPubMed

31.

Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK, et al. BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update. 2013;19(3):221–31. doi:10.1093/humupd/dms050.CrossRefPubMed

32.

Hammiche F, Laven JS, Boxmeer JC, Dohle GR, Steegers EA, Steegers-Theunissen RP. Sperm quality decline among men below 60 years of age undergoing IVF or ICSI treatment. J Androl. 2011;32(1):70–6. doi:10.2164/jandrol.109.009647.CrossRefPubMed

33.

Hansen ML, Thulstrup AM, Bonde JP, Olsen J, Hakonsen LB, Ramlau-Hansen CH. Does last week’s alcohol intake affect semen quality or reproductive hormones? A cross-sectional study among healthy young Danish men. Reprod Toxicol. 2012;34(3):457–62. doi:10.1016/j.reprotox.2012.06.004.CrossRefPubMed

34.

Lopez Teijon M, Garcia F, Serra O, Moragas M, Rabanal A, Olivares R, et al. Semen quality in a population of volunteers from the province of Barcelona. Reprod Biomed Online. 2007;15(4):434–44.CrossRefPubMed

35.

Martini AC, Molina RI, Estofan D, Senestrari D, Fiol de Cuneo M, Ruiz RD. Effects of alcohol and cigarette consumption on human seminal quality. Fertil Steril. 2004;82(2):374–7. doi:10.1016/j.fertnstert.2004.03.022.CrossRefPubMed

36.

Povey AC, Clyma JA, McNamee R, Moore HD, Baillie H, Pacey AA, et al. Modifiable and non-modifiable risk factors for poor semen quality: a case-referent study. Hum Reprod. 2012;27(9):2799–806. doi:10.1093/humrep/des183.CrossRefPubMed

37.

Jensen TK, Swan S, Jorgensen N, Toppari J, Redmon B, Punab M, et al. Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men from Europe and the USA. Hum Reprod. 2014;29(8):1801–9. doi:10.1093/humrep/deu118.CrossRefPubMedPubMedCentral

38.

Joo KJ, Kwon YW, Myung SC, Kim TH. The effects of smoking and alcohol intake on sperm quality: light and transmission electron microscopy findings. J Int Med Res. 2012;40(6):2327–35.CrossRefPubMed

39.

Kunzle R, Mueller MD, Hanggi W, Birkhauser MH, Drescher H, Bersinger NA. Semen quality of male smokers and nonsmokers in infertile couples. Fertil Steril. 2003;79(2):287–91 (pii: S0015028202046642).CrossRefPubMed

40.

Wallock LM, Tamura T, Mayr CA, Johnston KE, Ames BN, Jacob RA. Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers. Fertil Steril. 2001;75(2):252–9 (S0015-0282(00)01697-6).CrossRefPubMed

41.

Young SS, Eskenazi B, Marchetti FM, Block G, Wyrobek AJ. The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Hum Reprod. 2008;23(5):1014–22. doi:10.1093/humrep/den036.CrossRefPubMed

Title: Effect of Medications for Gastric Acid-Related Symptoms on Total Motile Sperm Count and Concentration: A Case–Control Study in Men of Subfertile Couples from the Netherlands
Authors: Nicole A. Huijgen
Hedwig J. Goijen
John M. Twigt
Annemarie G. M. G. J. Mulders
Jan Lindemans
Gert R. Dohle
Joop S. E. Laven
Régine P. M. Steegers-Theunissen
Publication date: 01-03-2017
Publisher: Springer International Publishing
Published in: Drug Safety / Issue 3/2017
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI: https://doi.org/10.1007/s40264-016-0488-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effect of Medications for Gastric Acid-Related Symptoms on Total Motile Sperm Count and Concentration: A Case–Control Study in Men of Subfertile Couples from the Netherlands

Abstract

Introduction

Objective

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2017

Hyperglycaemia Induced by Novel Anticancer Agents: An Undesirable Complication or a Potential Therapeutic Opportunity?

Benefits and Risks of Long-Term Asthma Management in Children: Where Are We Heading?

Developing a Crowdsourcing Approach and Tool for Pharmacovigilance Education Material Delivery

Cancer Event Rate and Mortality with Thienopyridines: A Systematic Review and Meta-Analysis

The Impact of Provider Networks on the Co-Prescriptions of Interacting Drugs: A Claims-Based Analysis

Proactive Regional Pharmacovigilance System Versus National Spontaneous Reporting for Collecting Safety Data on Concerning Off-Label Prescribing Practices: An Example with Baclofen and Alcohol Dependence in France