A Pilot Study Of The Prevalence Of Leg Pain Among Women With Endometriosis

Radiating leg pain is a common symptom presenting in manual therapy practices. Although this symptom has been reported as a complication of endometriosis, its prevalence and characteristics have not been studied. We surveyed members of a national endometriosis support group with endometriosis using a self-administered, mailed questionnaire. The main outcome measures were the prevalence and characteristics of leg pain. Of 94 respondents, leg pain was reported by 48 women (51%), and was bilateral in 59% of these symptomatic women. The likelihood of experiencing leg pain was related to weight gain since age 18, age, and height. The most common treatments tried included exercise, over-the-counter medications, and massage therapy, all with variable results. These data support leg pain as a prevalent complication of endometriosis, and that the disease may affect multiple peripheral nerves. Manual therapists should remain aware to this possible etiology for radiating pain

Air Pollution Exposures During Adulthood and Risk of Endometriosis in the Nurses’ Health Study II

Background: Particulate matter and proximity to large roadways may promote disease mechanisms, including systemic inflammation, hormonal alteration, and vascular proliferation, that may contribute to the development and severity of endometriosis. Objective: Our goal was to determine the association of air pollution exposures during adulthood, including distance to road, particulate matter < 2.5 μm, between 2.5 and 10 μm, and < 10 μm, (PM2.5, PM10–2.5, PM10), and timing of exposure with risk of endometriosis in the Nurses’ Health Study II. Methods: Proximity to major roadways and outdoor levels of PM2.5, PM10–2.5, and PM10 were determined for all residential addresses from 1993 to 2007. Multivariable-adjusted time-varying Cox proportional hazard models were used to estimate the relation between these air pollution exposures and endometriosis risk. Results: Among 84,060 women, 2,486 incident cases of surgically confirmed endometriosis were identified over 710,230 person-years of follow-up. There was no evidence of an association between endometriosis risk and distance to road or exposure to PM2.5, PM10–2.5, or PM10 averaged over follow-up or during the previous 2- or 4-year period. Conclusions: Traffic and air pollution exposures during adulthood were not associated with incident endometriosis in this cohort of women. Citation: Mahalingaiah S, Hart JE, Laden F, Aschengrau A, Missmer SA. 2014. Air pollution exposures during adulthood and risk of endometriosis in the Nurses’ Health Study II. Environ Health Perspect 122:58–64; http://dx.doi.org/10.1289/ehp.130662

Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999–2004

Background: Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited. Objective: We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20–54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999–2004. Methods: We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. Results: Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively. The ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77–2.41) for endometriosis, 1.56 (95% CI, 0.93–2.61) for leiomyomata, and 1.71 (95% CI, 1.07–2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19–1.02) for endometriosis, 0.63 (95% CI, 0.35–1.12) for leiomyomata, and 0.59 (95% CI, 0.37–0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed null associations for MEP and MBzP. Associations were similar when we excluded women diagnosed greater than 7 years before their NHANES evaluation. Conclusion: The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies

MR-guided focused ultrasound (MRgFUS) is effective for the distinct pattern of uterine fibroids seen in African-American women: data from phase III/IV, non-randomized, multicenter clinical trials

Background: Uterine fibroids are common among women at the reproductive age. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel and a conservative treatment for symptomatic cases. The aim of the study was to evaluate the efficacy of MRgFUS in African-American (AA) women compared with that in non-African-Americans (non-AA). Methods: A single-armed phase IV study was conducted to establish the efficacy of treatment in AA women. Comparison of patient, fibroid, and treatment characteristics from this trial was compared with that of the previously published phase III trial. Both studies were approved by the IRB of each medical center. Results: Sixty-three AA and 59 non-AA women were treated with MRgFUS. Although AA women had a different pattern of disease, outcomes were similar in both groups. AA patients had a significant higher total number of fibroids compared with non-AA (median 6.0, interquartile range (IQR) 3.0–10.0 vs. 2.0, IQR 1.0–4.0, respectively, p < 0.001), although their total fibroid volume was significantly smaller (median 196.9 cm3, IQR 112.8–415.3 cm3 vs. 394.8 cm3, IQR 189.8–674.4 cm3, respectively, p < 0.001). AA women were younger compared with non-AA (mean ± SD 43.4 ± 5.1 vs. 46.3 ± 4.1 years of age, respectively, p = 0.001) when they presented for treatment. The rate of alternative treatments as well as fibroid-associated symptoms at follow-up time points (3, 6, 12, 24, and 36 months, period following MRgFUS treatment) did not differ according to race (p ≥ 0.62). Conclusion: Despite differences in the pattern of fibroid disease, MRgFUS for uterine fibroids has a similar efficacy for AA women compared with non-AA women

Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999-2004

BACKGROUND. Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited. OBJECTIVE. We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20-54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999-2004. METHODS. We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS. Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively. The ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77-2.41) for endometriosis, 1.56 (95% CI, 0.93-2.61) for leiomyomata, and 1.71 (95% CI, 1.07-2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19-1.02) for endometriosis, 0.63 (95% CI, 0.35-1.12) for leiomyomata, and 0.59 (95% CI, 0.37-0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed null associations for MEP and MBzP. Associations were similar when we excluded women diagnosed > 7 years before their NHANES evaluation. CONCLUSION. The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies

Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10−8), including rs12700667 on 7p15.2 (P = 1.6 × 10−9), rs7521902 near WNT4 (P = 1.8 × 10−15), rs10859871 near VEZT (P = 4.7 × 10−15), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10−8), rs7739264 near ID4 (P = 6.2 × 10−10) and rs13394619 in GREB1 (P = 4.5 × 10−8). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10−8) and rs4141819 on 2p14 (P = 9.2 × 10−8). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways

Gestational carriers: A viable alternative for women with medical contraindications to pregnancy*

Objective: Compare the efficacy of surrogate or gestational carrier (GC) cycles to that of autologous in vitro fertilization (IVF)/intracytoplasmic sperm injections (ICSI) in patients with gynecologic or medical co-morbidities contraindicative to pregnancy. Design: Retrospective cohort study. Setting: Infertility patients from a single university hospital-based program from 1998-2009. Intervention(s) 128 GC cycles from 80 intended parents were identified and compared with 15,311 IVF or ICSI cycles. Main Outcome Measure(s) The peak estradiol (E2), number of oocytes retrieved, cycle cancellation, ongoing pregnancy, and live-birth were compared between GCs and autologous IVF carriers. Indications for GC use were also identified. Multiple cycles contributed by the same patient were accounted for using multivariable generalized estimating equations and two-sided Wald p-values. Results: Uterine factors (67%) was the most common indication for using a GC, followed by non-gynecologic medical conditions including coagulopathies (13%), end stage renal disease (10%), cardiovascular disease (5%) and cancer (5%). Adjusting for age, ovulation induction in GC cycles had similar peak E2 levels and number of oocytes retrieved relative to IVF cycles (p = 0.23 and 0.43, respectively). Clinical pregnancy (49% vs. 42%, p = 0.28) and live-birth rates (31% vs. 32%, p = 0.74) were also comparable. A sub-analysis of GC cycles in those women with uterine factor indications, demonstrated significantly higher clinical pregnancy rates (OR = 2.0; CI = 1.2 - 3.5) with 60% greater odds of live-birth relative to IVF/ICSI cycles, however this odds was not statistically significant for differences in live-birth (CI = 0.9 - 2.9). Conclusions: GCs are a viable alternative to start families for patients with medical co-morbidities precluding pregnancy