Plastic-related endocrine disrupting chemicals significantly related to the increased risk of estrogen-dependent diseases in women.

OBJECTIVE: To evaluate the association between exposure to plastic-related endocrine-disrupting chemicals (EDCs), specifically Bisphenol A (BPA), Phthalates, Cadmium, and Lead, and the risk of estrogen-dependent diseases (EDDs) such as polycystic ovary syndrome (PCOS), endometriosis, or endometrial cancer by conducting a meta-analysis of relevant studies. METHODS: PubMed, Web of Science, and Cochrane Library databases were used for literature retrieval of articles published until the 21st of April 2023. Literature that evaluated the association between BPA, phthalates, cadmium, and/or lead exposure and the risk of PCOS, endometriosis, or endometrial cancer development or exacerbation were included in our analysis. STATA/MP 17.0 was used for all statistical analyses. RESULTS: Overall, 22 articles were included in our meta-analysis with a total of 83,641 subjects all of whom were females aged between 18 and 83 years old. The overall effect size of each study was as follows: endometriosis risk in relation to BPA exposure ES 1.82 (95% CI; 1.50, 2.20). BPA and PCOS risk ES 1.61 (95% CI; 1.39, 1.85). Phthalate metabolites and endometriosis risk; MBP ES 1.07 (95% CI; 0.86, 1.33), MEP ES 1.05 (95% CI; 0.87, 1.28), MEHP ES 1.15 (95% CI; 0.67, 1.98), MBzP ES 0.97 (95% CI; 0.63, 1.49), MEOHP ES 1.87 (95% CI; 1.21, 2.87), and MEHHP ES 1.98 (95% CI; 1.32, 2.98). Cadmium exposure and endometrial cancer risk ES 1.14 (95% CI; 0.92, 1.41). Cadmium exposure and the risk of endometriosis ES 2.54 (95% CI; 1.71, 3.77). Lead exposure and the risk of endometriosis ES 1.74 (95% CI; 1.13, 2.69). CONCLUSION: Increased serum, urinary, or dietary concentration of MBzP and MEHP in women is significantly associated with endometriosis risk. Increased cadmium concentration is associated with endometrial cancer risk.

Periodontal disease severity and cancer risk in postmenopausal women: the Buffalo OsteoPerio Study.

PURPOSE: Few prospective studies have reported on relationships between objective periodontal disease (PD) measures and cancer risk. This association was examined in 1,337 postmenopausal women participating in the Buffalo OsteoPerio Study. METHODS: Oral alveolar crestal height (ACH) was measured using oral radiographs. Incident cancers were adjudicated with medical records. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between ACH and incident cancer outcomes were estimated using Cox proportional hazards models. RESULTS: There were 203 confirmed total incident cancer cases during follow-up (12.2 ± 4.2 years). After adjusting for age and smoking, there were no statistically significant associations between ACH-defined PD categories and total cancer risk (mild/moderate vs. none: HR 1.33, 95 % CI 0.91-1.94; severe vs. none: HR 1.20, 95 % CI 0.77-1.86). ACH-defined PD categories were not associated with common site-specific cancers. Whole-mouth mean and worst-site ACH (per 1 mm loss) were significantly associated with increased risk of lung (adjusted HR 1.81, 95 % CI 1.30-2.54; adjusted HR 1.34, 95 % CI 1.08-1.66, respectively), but not total or other site-specific cancer. Smoking status modified the associations between continuous ACH variables and total cancer risk; measures of PD were associated with total cancer among smokers but not never smokers (interaction p = 0.02 and p < 0.01 for whole-mouth mean and worst-site ACH, respectively). CONCLUSIONS: ACH-defined PD was associated with total cancer risk in ever but not never smoking postmenopausal women. Whole-mouth mean and worst-site ACH were associated with increased lung cancer risk. However, these results need to be interpreted cautiously given the small number of lung cancer cases (n = 18). Further research utilizing a larger sample is warranted to confirm the relationships among oral bone loss, site-specific cancers, and total cancer.

Evaluation of pegylated liposomal doxorubicin dose on the adverse drug event profile and outcomes in treatment of recurrent endometrial cancer.

OBJECTIVE: This study aims to determine factors that may increase the likelihood of adverse drug events (ADEs) in patients with recurrent endometrial cancer treated with pegylated liposomal doxorubicin (PLD) as well as this agent's impact on clinical outcomes. METHODS: The treatment records of patients with endometrial cancer who received PLD at The University of Texas, MD Anderson Cancer Center, from 1996 to 2006 were reviewed. Patient demographics, PLD dose, ADEs, use of supportive care interventions, disease progression, and survival were extracted. Logistical regression analysis was used to identify factors that were associated with higher incidence of ADEs and that influenced survival. RESULTS: A total of 60 patients with recurrent endometrial cancer were identified who experienced 122 ADEs. The most commonly reported ADEs were nausea (18.9%), palmar-plantar erythrodysesthesia (PPE; 16.4%), muscle weakness (12.3%), mucositis (10.7%), and peripheral neuropathy (9.8%). Seventeen patients (28%) required a dose reduction because of ADEs. However, only 5 (8.3%) patients discontinued therapy because of toxicity. Cooling mechanisms were used in 19 patients to prevent PPE, although 9 of these patients still experienced PPE. Treatment with 6 or more cycles of PLD was associated with increased incidence of neutropenia (P = 0.045), peripheral neuropathy (P = 0.004), and PPE (P < 0.001). No differences in progression-free survival or time to progression were found between the doses of PLD; however, there was an assessable trend toward increased survival with doses of 40 mg/m(2). CONCLUSIONS: Although there was no association with dose level and ADEs, more cycles received increased the incidence of toxicities, including PPE and neuropathy. There was no association between different doses of PLD and progression-free survival or time to progression.

Fiber intake and endometrial cancer risk.

BACKGROUND: The epidemiological evidence on the relation between dietary fiber intake and endometrial cancer is contradictory. Consequently, a case-control study was carried out to further investigate the role of dietary fiber intake in the etiology of endometrial cancer. MATERIAL AND METHODS: Cases were 454 women with incident, histologically confirmed, endometrial cancer admitted to major teaching and general hospitals. Controls were 908 women admitted for acute, non-neoplastic conditions to the same hospital network. Information on diet was elicited using a validated food frequency questionnaire. RESULTS: Odds ratios (OR) and 95% confidence intervals (CI) for quintiles of various types of fiber were estimated after allowance for total energy intake and other potential confounding factors. Lignin intake was significantly inversely related to endometrial cancer (OR=0.6 for the highest versus the lowest quintile of intake; 95%CI: 0.4-0.9) with a slightly significant linear trend in risk (p-value=0.04). DISCUSSION: Data suggest the potential importance of lignin in the prevention of endometrial cancer at Italian consumption levels.

EVALUATION AND MANAGEMENT OF DIFFICULT AIRWAY IN OBESITY A SINGLE CENTER RETROSPECTIVE STUDY.

The primary aim of this single center retrospective study was to evaluate difficult mask ventilation (DMV) and difficult laryngoscopy (DL) in a unique group of obese patients. A total of 427 adult patients with body mass index (BMI) ≥ 25 and surgically treated for endometrial cancer from 2011 to 2014 were assessed. Additional increase in BMI, comorbidities, bedside screening tests for risk factors, and the tools used to manage the patients were noted and their effects on DMV and/or DL investigated. Every escalation in the number of risk factors increased the probability of DMV 2.2-fold, DL 1.8-fold and DMV+DL 3.0-fold. Among bedside tests, limited neck movement (LNM), short neck (SN) and absence of teeth were significant for DMV (p < 0.05), LNM, SN and obstructive sleep apnea for DL (p < 0.05), and LNM and SN for DMV+DL (p < 0.05). However, a 10-point increase of BMI was not an independent risk factor when patients with BMI > 25% were considered. In conclusion, LNM and SN are independent risk factors for developing DMV and/or DL in obese endometrial cancer patients, while BMI increase over 30 was not additionally affecting difficult airway.

Progestins and menopause: epidemiological studies of risks of endometrial and breast cancer.

Estrogen replacement therapy (ERT) increases a woman's risk of developing endometrial cancer approximately 120% for each 5 years of use. ERT increases a woman's risk of developing breast cancer approximately 10% for each 5 years of use. To reduce the greatly increased endometrial cancer risk, progestins have been added to ERT (estrogen-progestin replacement therapy; EPRT) for between 5 and 15 days (usually 7 or 10 days) per month in a sequential fashion (sequential EPRT; SEPRT) or with each dose of ERT (continuous-combined EPRT; CEPRT). We conducted two large case-control studies in postmenopausal women in Los Angeles to evaluate the effects of these changes on endometrial and breast cancer risks. As expected CEPRT was not associated with any increased risk of endometrial cancer. SEPRT with the progestin being given for 10 days per month also did not increase endometrial cancer risk. SEPRT with the progestin being given for 7 days per month did increase endometrial cancer risk with only a relatively slight reduction in risk compared to ERT effectively proportional to the reduction in the number of days of unopposed estrogen. The sharp contrast between the effects of 7 days and 10 days of progestin in SEPRT suggests that the extent of endometrial sloughing or of 'terminal' differentiation at the completion of the progestin phase may play a critical role in determining endometrial cancer risk. This may provide an explanation of why endometrial cancer risk increases so sharply with age in young women even in countries where obesity-associated anovulation is very uncommon; extended periods of unopposed estrogen is not an explanation but less than 10 days of an 'adequate' progesterone level may be. EPRT significantly increased the risk of breast cancer. EPRT was associated with an approximately 24% increase in risk for each 5 years of use; the effect was some 212-fold greater than the effect of ERT, which we had previously predicted on theoretical grounds. This effect could also be predicted from the results on mammographic densities seen in the PEPI randomized trial of different forms of hormone replacement therapy (HRT). In the PEPI trial EPRT increased mammographic densities to a much greater extent than ERT. Progestins need to be given to protect the endometrium. They need to be delivered to the endometrium in a manner that will have the least effect on the breast. This can be carried out by using a vaginal or direct endometrial route of administration. The vaginal route will provide adequate endometrial progestin levels with low blood levels so that the effects of the progestin on the breast should be small; with the direct endometrial route the blood progestin levels are even lower, and the effects of the progestin on the breast will be effectively zero. If this is unacceptable to a woman, then giving progestins by mouth (or transdermally) for 10 days every 3 to 4 months should provide satisfactory protection of the endometrium when used with standard-dose conjugated estrogen (CE). This regimen has much less effect on the breast than monthly SEPRT or CEPRT. Two clinical trials of 10 mg per day of MPA for 14 days every 3 months and 0.625 mg/day of CE have been published. Both studies suggest that this approach may be satisfactory in that the extent of hyperplasia was minimal. More studies of this approach are urgently needed.

Practical aspects of hormone replacement therapy.

Menopause is an endocrinopathy characterized by hypoestrogenism. Estrogen can be replaced easily. Available preparations can be taken by mouth, intramuscularly, transdermally, or transvaginally. Unopposed estrogens increase the risk of endometrial cancer, which can be overcome by the concomitant administration of a progestin agent. The progestin can be administered cyclically either every month, resulting in a monthly menses, or every 3 months, resulting in menses every 3 months. The progestin can also be administered every day, which achieves amenorrhea in over half of the patients; the remainder have breakthrough bleeding. Abnormal bleeding can be assessed by either endometrial biopsy or transvaginal ultrasound.