Associations between urinary biomarkers of phthalates and phthalate alternatives and female sexual function in a North American cohort.

BACKGROUND

Phthalates are endocrine-disrupting chemicals that can dysregulate hormonal systems supporting female sexual function (eg, estrogen interference). Female sexual function is important for positive sexual expression, fertility, and well-being but remains understudied in the context of environmental toxicants to which females are ubiquitously exposed. Identifying environmental determinants of female sexual dysfunction can inform exposure-reduction strategies and clinical practice to improve sexual health.

AIM

We investigated associations between phthalate exposure and sexual function in a cohort of North American females.

METHODS

We leveraged cross-sectional data from a subset of 21-45-year-old females trying to conceive enrolled in Pregnancy Study Online (n = 347) to assess associations between phthalate and phthalate alternative exposure and sexual function, measured on a modified version of the Female Sexual Function Index-6 (FSFI-6). We summed FSFI-6 responses (range = 2-30); lower scores reflected poorer function. We measured urinary concentrations of 18 phthalate and alternative metabolites using online solid phase extraction coupled with high-performance liquid chromatography isotope dilution tandem mass spectrometry. Given that the biomarkers were nonlinearly associated with FSFI-6 scores, we categorized creatinine-corrected biomarker concentrations in tertiles. We used multivariable linear regression to estimate mean differences (β) with 95% confidence intervals (CIs) in FSFI-6 scores per tertile increase in biomarker concentrations, adjusting for hypothesized confounders. In secondary analyses, we considered individual FSFI-6 items (range = 1-5) as outcome variables.

OUTCOMES

Female sexual function measured on the FSFI-6.

RESULTS

Most biomarkers were not associated with FSFI-6 scores. Mono-n-butyl phthalate concentrations were weakly and non-monotonically associated with lower summed FSFI-6 scores (β = -0.8, 95% CI = -1.8, 0.2) and orgasm scores (β = -0.3, 95% CI = -0.7, 0.1) at the second (vs first) tertile, reflecting poorer sexual function. Mono-2-ethyl-5-carboxypentyl terephthalate concentrations were weakly associated with poorer scores for orgasm, while other biomarkers (notably, mono-carboxyisononyl phthalate) were associated with higher summed FSFI-6 and FSFI-6 item scores.

CLINICAL IMPLICATIONS

Exposure to phthalates should be considered in clinical settings, particularly for females experiencing issues with sexual function.

STRENGTHS AND LIMITATIONS

This study represents one of the first to assess associations of phthalate exposure and female sexual function, and we investigated associations in an established cohort with a validated measure of sexual function. We were limited by our sample size and cross-sectional study design.

CONCLUSION

Although associations for most phthalate biomarkers were null, some were weakly associated with female sexual function, suggesting exposure to certain chemicals may affect female sexual function with implications for clinical practice and exposure reduction strategies.