Association between use of phthalate-containing medication and semen quality among men in couples referred for assisted reproduction

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Abstract

STUDY QUESTION Does phthalate exposure from prescription drugs affect semen quality? SUMMARY ANSWER Exposure to phthalate-containing drugs is associated with poor semen quality. WHAT IS KNOWN ALREADY Phthalates and their metabolites have been shown to disrupt the hormone signalling in animal studies. One study has shown associations between medicinal phthalate exposure and poor semen quality, suggesting similar effects in humans. STUDY DESIGN, SIZE, DURATION We included 18 515 males with poor semen quality (cases) and 31 063 males with normal semen quality (controls) registered in the Danish IVF Registry from 2006 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Exposure to phthalate-containing drugs was assessed from the Danish Register of Medicinal Product Statistics. Outcome measures were obtained at the first contact with the fertility clinic, and categorized according to the International Classification of Diseases (ICD-10). The association between current use of phthalate-containing medications <90 days prior to semen sampling and reduced semen quality was analysed using unconditional logistic regression, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE In total, 57 cases and 72 controls redeemed at least one prescription for a drug containing ortho-phthalates in the 90 days before their first semen sample, yielding an adjusted odds ratio (OR) of 1.30 (95% CI: 0.91-1.85) for poor semen quality when compared to males exposed to phthalate-free generic drugs. Similarly, 81 cases and 78 controls exposed to a drug containing polymers had increased odds of poor semen quality (OR = 1.71, 95% CI: 1.24-2.35). Current exposure to polymer containing products from alimentary tract and metabolism drugs was associated with the highest OR of 2.80 (95% CI: 1.63-4.84). Comparing males exposed to drugs containing ortho-phthalates or polymers with males unexposed to prescription drugs, we found adjusted ORs of 1.32 (95% CI: 0.93-1.87) and 1.73 (95% CI: 1.26-2.36), respectively. We saw no clear relationship between degree of exposure and odds of poor semen quality. LIMITATIONS, REASONS FOR CAUTION The reliance on ICD-10 based register data restricted our ability to relate phthalate exposure to detailed semen parameters. Furthermore, due to imperfections in the registry, we could only include the first semen sample and could not follow semen quality over time. WIDER IMPLICATIONS OF THE FINDINGS Our results support the likely negative effect of phthalate exposure from medicinal drugs on semen quality. As exposures from medicinal products are readily avoidable, our findings may be of relevance to regulatory authorities. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by Odense University Hospital, Denmark (Grant number A1003). None of the authors declare conflict of interest.

Original languageEnglish
JournalHuman Reproduction
Volume33
Issue number3
Pages (from-to)503–511
ISSN0268-1161
DOIs
Publication statusPublished - 1. Mar 2018

Fingerprint

Semen
International Classification of Diseases
Pharmaceutical Preparations
Odds Ratio
Registries
phthalic acid
Generic Drugs
Conflict of Interest
Denmark
Logistic Models
Outcome Assessment (Health Care)
Hormones

Keywords

  • Adult
  • Denmark
  • Environmental Exposure
  • Fertilization in Vitro
  • Humans
  • Male
  • Phthalic Acids/analysis
  • Prescription Drugs/chemistry
  • Registries
  • Semen Analysis
  • Sperm Count
  • Spermatozoa/drug effects

Cite this

@article{3a58ab88be174387a07164ff136728a4,
title = "Association between use of phthalate-containing medication and semen quality among men in couples referred for assisted reproduction",
abstract = "STUDY QUESTION Does phthalate exposure from prescription drugs affect semen quality? SUMMARY ANSWER Exposure to phthalate-containing drugs is associated with poor semen quality. WHAT IS KNOWN ALREADY Phthalates and their metabolites have been shown to disrupt the hormone signalling in animal studies. One study has shown associations between medicinal phthalate exposure and poor semen quality, suggesting similar effects in humans. STUDY DESIGN, SIZE, DURATION We included 18 515 males with poor semen quality (cases) and 31 063 males with normal semen quality (controls) registered in the Danish IVF Registry from 2006 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Exposure to phthalate-containing drugs was assessed from the Danish Register of Medicinal Product Statistics. Outcome measures were obtained at the first contact with the fertility clinic, and categorized according to the International Classification of Diseases (ICD-10). The association between current use of phthalate-containing medications <90 days prior to semen sampling and reduced semen quality was analysed using unconditional logistic regression, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE In total, 57 cases and 72 controls redeemed at least one prescription for a drug containing ortho-phthalates in the 90 days before their first semen sample, yielding an adjusted odds ratio (OR) of 1.30 (95{\%} CI: 0.91-1.85) for poor semen quality when compared to males exposed to phthalate-free generic drugs. Similarly, 81 cases and 78 controls exposed to a drug containing polymers had increased odds of poor semen quality (OR = 1.71, 95{\%} CI: 1.24-2.35). Current exposure to polymer containing products from alimentary tract and metabolism drugs was associated with the highest OR of 2.80 (95{\%} CI: 1.63-4.84). Comparing males exposed to drugs containing ortho-phthalates or polymers with males unexposed to prescription drugs, we found adjusted ORs of 1.32 (95{\%} CI: 0.93-1.87) and 1.73 (95{\%} CI: 1.26-2.36), respectively. We saw no clear relationship between degree of exposure and odds of poor semen quality. LIMITATIONS, REASONS FOR CAUTION The reliance on ICD-10 based register data restricted our ability to relate phthalate exposure to detailed semen parameters. Furthermore, due to imperfections in the registry, we could only include the first semen sample and could not follow semen quality over time. WIDER IMPLICATIONS OF THE FINDINGS Our results support the likely negative effect of phthalate exposure from medicinal drugs on semen quality. As exposures from medicinal products are readily avoidable, our findings may be of relevance to regulatory authorities. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by Odense University Hospital, Denmark (Grant number A1003). None of the authors declare conflict of interest.",
keywords = "Adult, Denmark, Environmental Exposure, Fertilization in Vitro, Humans, Male, Phthalic Acids/analysis, Prescription Drugs/chemistry, Registries, Semen Analysis, Sperm Count, Spermatozoa/drug effects",
author = "Anne Broe and A Potteg{\aa}rd and Jesper Hallas and Thomas Ahern and Jens Fedder and Per Damkier",
note = "{\circledC} The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com",
year = "2018",
month = "3",
day = "1",
doi = "10.1093/humrep/dey009",
language = "English",
volume = "33",
pages = "503–511",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Heinemann",
number = "3",

}

Association between use of phthalate-containing medication and semen quality among men in couples referred for assisted reproduction. / Broe, Anne; Pottegård, A; Hallas, Jesper; Ahern, Thomas; Fedder, Jens ; Damkier, Per.

In: Human Reproduction, Vol. 33, No. 3, 01.03.2018, p. 503–511.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Association between use of phthalate-containing medication and semen quality among men in couples referred for assisted reproduction

AU - Broe, Anne

AU - Pottegård, A

AU - Hallas, Jesper

AU - Ahern, Thomas

AU - Fedder, Jens

AU - Damkier, Per

N1 - © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

PY - 2018/3/1

Y1 - 2018/3/1

N2 - STUDY QUESTION Does phthalate exposure from prescription drugs affect semen quality? SUMMARY ANSWER Exposure to phthalate-containing drugs is associated with poor semen quality. WHAT IS KNOWN ALREADY Phthalates and their metabolites have been shown to disrupt the hormone signalling in animal studies. One study has shown associations between medicinal phthalate exposure and poor semen quality, suggesting similar effects in humans. STUDY DESIGN, SIZE, DURATION We included 18 515 males with poor semen quality (cases) and 31 063 males with normal semen quality (controls) registered in the Danish IVF Registry from 2006 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Exposure to phthalate-containing drugs was assessed from the Danish Register of Medicinal Product Statistics. Outcome measures were obtained at the first contact with the fertility clinic, and categorized according to the International Classification of Diseases (ICD-10). The association between current use of phthalate-containing medications <90 days prior to semen sampling and reduced semen quality was analysed using unconditional logistic regression, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE In total, 57 cases and 72 controls redeemed at least one prescription for a drug containing ortho-phthalates in the 90 days before their first semen sample, yielding an adjusted odds ratio (OR) of 1.30 (95% CI: 0.91-1.85) for poor semen quality when compared to males exposed to phthalate-free generic drugs. Similarly, 81 cases and 78 controls exposed to a drug containing polymers had increased odds of poor semen quality (OR = 1.71, 95% CI: 1.24-2.35). Current exposure to polymer containing products from alimentary tract and metabolism drugs was associated with the highest OR of 2.80 (95% CI: 1.63-4.84). Comparing males exposed to drugs containing ortho-phthalates or polymers with males unexposed to prescription drugs, we found adjusted ORs of 1.32 (95% CI: 0.93-1.87) and 1.73 (95% CI: 1.26-2.36), respectively. We saw no clear relationship between degree of exposure and odds of poor semen quality. LIMITATIONS, REASONS FOR CAUTION The reliance on ICD-10 based register data restricted our ability to relate phthalate exposure to detailed semen parameters. Furthermore, due to imperfections in the registry, we could only include the first semen sample and could not follow semen quality over time. WIDER IMPLICATIONS OF THE FINDINGS Our results support the likely negative effect of phthalate exposure from medicinal drugs on semen quality. As exposures from medicinal products are readily avoidable, our findings may be of relevance to regulatory authorities. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by Odense University Hospital, Denmark (Grant number A1003). None of the authors declare conflict of interest.

AB - STUDY QUESTION Does phthalate exposure from prescription drugs affect semen quality? SUMMARY ANSWER Exposure to phthalate-containing drugs is associated with poor semen quality. WHAT IS KNOWN ALREADY Phthalates and their metabolites have been shown to disrupt the hormone signalling in animal studies. One study has shown associations between medicinal phthalate exposure and poor semen quality, suggesting similar effects in humans. STUDY DESIGN, SIZE, DURATION We included 18 515 males with poor semen quality (cases) and 31 063 males with normal semen quality (controls) registered in the Danish IVF Registry from 2006 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Exposure to phthalate-containing drugs was assessed from the Danish Register of Medicinal Product Statistics. Outcome measures were obtained at the first contact with the fertility clinic, and categorized according to the International Classification of Diseases (ICD-10). The association between current use of phthalate-containing medications <90 days prior to semen sampling and reduced semen quality was analysed using unconditional logistic regression, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE In total, 57 cases and 72 controls redeemed at least one prescription for a drug containing ortho-phthalates in the 90 days before their first semen sample, yielding an adjusted odds ratio (OR) of 1.30 (95% CI: 0.91-1.85) for poor semen quality when compared to males exposed to phthalate-free generic drugs. Similarly, 81 cases and 78 controls exposed to a drug containing polymers had increased odds of poor semen quality (OR = 1.71, 95% CI: 1.24-2.35). Current exposure to polymer containing products from alimentary tract and metabolism drugs was associated with the highest OR of 2.80 (95% CI: 1.63-4.84). Comparing males exposed to drugs containing ortho-phthalates or polymers with males unexposed to prescription drugs, we found adjusted ORs of 1.32 (95% CI: 0.93-1.87) and 1.73 (95% CI: 1.26-2.36), respectively. We saw no clear relationship between degree of exposure and odds of poor semen quality. LIMITATIONS, REASONS FOR CAUTION The reliance on ICD-10 based register data restricted our ability to relate phthalate exposure to detailed semen parameters. Furthermore, due to imperfections in the registry, we could only include the first semen sample and could not follow semen quality over time. WIDER IMPLICATIONS OF THE FINDINGS Our results support the likely negative effect of phthalate exposure from medicinal drugs on semen quality. As exposures from medicinal products are readily avoidable, our findings may be of relevance to regulatory authorities. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by Odense University Hospital, Denmark (Grant number A1003). None of the authors declare conflict of interest.

KW - Adult

KW - Denmark

KW - Environmental Exposure

KW - Fertilization in Vitro

KW - Humans

KW - Male

KW - Phthalic Acids/analysis

KW - Prescription Drugs/chemistry

KW - Registries

KW - Semen Analysis

KW - Sperm Count

KW - Spermatozoa/drug effects

U2 - 10.1093/humrep/dey009

DO - 10.1093/humrep/dey009

M3 - Journal article

VL - 33

SP - 503

EP - 511

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 3

ER -