In a review article published on August 8, 2016 in the peer-reviewed journal Environment International, Melissa Mariana and colleagues from Health Sciences Research Centre, University of Beira Interior, Portugal, summarize the knowledge on how phthalates are metabolized in humans, and discuss the evidence from epidemiological studies and animal experiments on the reproductive and cardiovascular effects of these compounds.

In regard to the male reproductive system, the results of epidemiological studies were judged to be very variable, possibly due to different study populations and different endpoints examined. Due to this variability, the authors concluded that “there is not enough consistent data that relates human exposure to phthalates with hypospadias and cryptorchidism, and the relation between phthalates and AGD [anogenital distance] is weak.” For sperm, the most consistent evidence for an association with lower semen quality was found for di(2-ethylhexyl) phthalate (DEHP, CAS 117-81-7) and di-n-butyl phthalate (DBP, CAS 84-74-2).

In regard to the female reproductive system, no evidence was found in support of an association between phthalate exposure and precocious puberty. An association between phthalates and endometriosis has been suggested, but more studies are needed to reach a definite conclusion on this link. Significant evidence was found for phthalates’ association with reduced gestational time, but not for the effects of phthalates on birth size.

An association between blood levels of several phthalate metabolites and cardiovascular disease risk factors was found in the sole study performed on this issue so far. One other study has related urinary levels of mono(2-ethylhexyl) phthalate (MEHP, CAS 4376-20-9), a metabolite of DEHP, to atherosclerosis, and several more studies have examined the link between phthalate exposure and hypertension. Overall, the authors concluded that “evidence points to an increased cardiovascular risk from exposure to phthalates”, but further research is required to better understand the effects and mechanisms.

The authors suggest that, in order to deliver useful additional information on the health risks of exposure to phthalates, future epidemiological studies should have a large study population and address the issues of contamination and proper sampling strategies. Furthermore, to understand the sources of high variability observed previously, the authors suggest to carry out comparative studies in different phthalate-exposed populations to better understand the influence of exposure types and/or genetic background on the observed responses to phthalates exposure.


Mariana, M., et al. (2016). “The effects of phthalates in the cardiovascular and reproductive systems: A review.Environment International (published August 8, 2016).