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

Hum Reprod. 2018 Mar 1;33(3):503-511. doi: 10.1093/humrep/dey009.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Phthalic Acids
  • Prescription Drugs
  • phthalic acid