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Objectives. To examine the association between phthalates exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume. Design: Pilot, cross-sectional study Setting: Academic medical center Patient(s): Fifty-seven pre-menopausal women undergoing either hysterectomy or myomectomy for fibroids. Intervention: None Main Outcome Measures: Diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual phthalate metabolites, sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP), and a weighted sum of anti-androgenic phthalate metabolites (∑AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and BMI. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression. Results. Most women were Black, overweight or obese, and college-educated. In multivariable models, higher levels of mono-hydroxyisobutyl phthalate, monocarboxyoctyl phthalate,monocarboxynonyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), ∑DEHP and ∑AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites(MEHHP, MEOHP, MECPP), ∑DEHP and ∑AA Phthalates. For example, a doubling in ∑DEHP and ∑AA Phthalates was associated with 33.19% (95% CI 6.59, 66.43) and 26.81% (95% CI 2.19, 57.37) increase in uterine volume, respectively. There were few associations between phthalate biomarkers and fibroid size. Conclusions. Exposure to some phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that phthalates exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.

Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (β = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (β = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (q interaction < 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids.

Background and Objectives:To assess the feasibility and safety of minimally invasive hysterectomy for uteri >1 kg.Methods:Clinical and surgical characteristics were collected for patients in an academic tertiary care hospital. Included were patients who underwent minimally invasive hysterectomy by 1 of 3 fellowship-trained gynecologists from January 1, 2009, to July 1, 2015 and subsequently had confirmed uterine weights of 1 kg or greater on pathology report. Both robotic and conventional laparoscopic procedures were included.Results:During the study period, 95 patients underwent minimally invasive hysterectomy with confirmed uterine weight over 1 kg. Eighty-eight percent were performed with conventional laparoscopy and 12.6% with robot-assisted laparoscopy. The median weight (range) was 1326 g (range, 1000–4800). The median estimated blood loss was 200 mL (range, 50–2000), and median operating time was 191 minutes (range, 75–478). Five cases were converted to laparotomy (5.2%). Four cases were converted secondary to hemorrhage and one secondary to extensive adhesions. There were no conversions after 2011. Intraoperative transfusion was given in 6.3% of cases and postoperative transfusion in 6.3% of cases. However, after 2013, the rate of intraoperative transfusion decreased to 1.0% and postoperative transfusion to 2.1%. Of the 95 cases, there were no cases with malignancy.Conclusions:This provides the largest case series of hysterectomy over 1 kg completed by a minimally invasive approach. Our complication rate improved with experience and was comparable to other studies of minimally invasive hysterectomy for large uteri. When performed by experienced surgeons, minimally invasive hysterectomy for uteri >1 kg can be considered feasible and safe.

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