Abstract
Fibroid etiology is poorly understood but is likely hormonally mediated. Therefore, we evaluated associations between midlife phthalates (hormone-altering chemicals) and prior fibroid diagnosis, and considered differences by weight gain status. Women (ages: 45–54; n = 754) self-reported past fibroid diagnosis. We pooled 1–4 urines collected after fibroid diagnosis over the consecutive weeks to analyze nine phthalate metabolites and calculate relevant molar sums (e.g., di(2-ethylhexyl) phthalate, ΣDEHP; anti-androgenic phthalates, ΣAA; all metabolites, ΣPhthalates). Using Poisson regression, we evaluated associations between phthalate biomarkers and the risk of having fibroid diagnosis. We explored if associations differed by weight gain from age 18 to 45–54 or in women diagnosed with fibroids within 5 years of phthalate assessment. Our major finding was that women had a 13% (RR: 1.13; 95%CI: 1.02, 1.26) and 16% (RR: 1.16; 95% CI: 1.03, 1.31) greater risk of prior fibroid diagnosis for each two-fold increase in ΣDEHP or ΣAA, respectively. These associations were strongest in women who became overweight/obese from age 18 to 45–54 and in those diagnosed <5 years before phthalate assessment. Based on these results, prospective studies should corroborate our findings related to associations between phthalates and fibroids, and may consider evaluating the role that weight gain may play in these associations.
Highlights
We evaluated the timing of fibroid diagnosis as a three-level variable using the following categories: women who were diagnosed with fibroids within five years of the baseline visit, those diagnosed with fibroids five years or more before the baseline visit, and those never diagnosed with fibroids
We observed that ΣDEHP was associated with a higher risk of prior fibroid diagnosis, which was the main contributor to the associations between ΣPlastics, ΣPhthalates, and ΣAA and prior fibroid diagnosis
In sensitivity analyses assessing the timing of fibroid diagnosis relative to midlife urine collection for phthalate biomarker assessment, we found that associations of ΣDEHP and related phthalate molar sums with higher likelihood of prior fibroid diagnosis were stronger in women diagnosed within five years of urine collection
Summary
Most women will have uterine leiomyomata, commonly known as fibroids, which are non-cancerous tumors of uterine smooth muscle cells associated with adverse health outcomes, including abnormal uterine bleeding and miscarriage [1–3]. Fibroids almost exclusively occur in reproductive-aged, pre- and perimenopausal women, with incidence increasing with age until women are post-menopausal [2,4,5]. The exact prevalence of fibroids is difficult to determine because of the spectrum of clinical presentation. Many women with fibroids have a benign presentation, where fibroids are incidentally detected during imaging, whereas up to half of women with fibroids experience
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