Differences in characteristics and use of complementary and alternative methods for coping with endometriosis-associated acyclic pelvic pain across adolescence and adulthood.

Introduction: Over four million women in the US alone have been diagnosed with endometriosis. For those living with this disease, surgery and hormonal treatment reduce associated pelvic pain in some, while others continue to experience life impacting pain. Therefore, identification of accessible and cost-effective methods of pain reduction to compliment current treatment is urgently needed. Our objective was to quantify the prevalence of complementary and alternative methods used to manage acyclic pelvic pain and their reported benefit among women of different age groups living with endometriosis. Methods: We used baseline questionnaire data from laparoscopically-confirmed endometriosis cases who completed a WERF EPHect compliant questionnaire in the longitudinal cohort of The Women's Health Study: From Adolescence to Adulthood (A2A). Participants with acyclic pelvic pain were asked to indicate specific methods or activities that either helped or worsened their pelvic/lower abdominal pain. Differences among age groups [adolescent (<18 years), young adult (18-25 years), and adult (>25 years)] were assessed using Fisher's exact test. Results: Of the 357 participants included in analysis, sleep for coping was reported more frequently among adolescents (n = 59, 57.3%) compared to young adults (n = 40, 44.0%) and adults (n = 19, 31.1%; p = 0.004). Adolescents also reported more frequent use of music (n = 29, 21.2%) than young adults (n = 10, 7.0%) and adults (n = 7, 9.1%; p = 0.001). Exercise worsened pain most commonly among adolescents (n = 82, 59.9%), followed by younger adults (n = 67, 46.9%), and adults (n = 27, 35.1%; p = 0.002). Discussion: Our analysis of participants in the A2A cohort showed that the prevalence of complementary and alternative methods used for coping with endometriosis-associated acyclic pelvic pain varied by age group. Future studies should aim to provide information that will further inform decisions in making care plans for managing endometriosis-associated pain that is effective, accessible, and tailored to the preferences of the patient.

Dietary fat intake, erythrocyte fatty acids, and risk of uterine fibroids.

OBJECTIVE: To prospectively evaluate the association between dietary fat intake and risk of uterine fibroids; and to evaluate the association between erythrocyte membrane fatty acid (FA) levels and fibroid risk. DESIGN: Prospective cohort study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence interval (CI). In a subset of participants 34 individual FAs were measured and logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI for the association between FA tertiles and fibroids. SETTING: Not applicable. PATIENT(S): Premenopausal US women (81,590) in the Nurses' Health Study II, aged 25-42 years at enrollment in 1989 for whom diet was assessed by a food frequency questionnaire. A total of 553 participants with erythrocyte FA measurements. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cases of fibroids were defined on the basis of self-reported ultrasound or hysterectomy confirmation. RESULT(S): A total of 8,142 cases of ultrasound-confirmed or hysterectomy-confirmed were diagnosed during an 18-year period (1991-2009). No associations were observed between intake of any dietary fats and fibroids in the multivariable models. However, when erythrocyte FAs were examined, an inverse association was observed between total n-3 polyunsaturated FAs and likelihood of fibroids (OR for third versus first tertile, 0.41; 95% CI 0.19-0.89). In addition, total trans FAs were associated with more odds of fibroids (OR for third tertile, 3.33; 95% CI 1.50-7.38). CONCLUSION(S): Our findings provide preliminary suggestions that n-3 polyunsaturated FAs and trans FAs may play a role in fibroid etiology; however, these results should be confirmed in future studies.

Supplementation with vitamin D or ω-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Adolescents with endometriosis are a particularly underserved population who struggle with chronic pain. Despite widespread use, there are no published trials examining the individual effects of vitamin D and omega-3 (n-3) fatty acid supplementation on endometriosis-associated pain in adolescents. OBJECTIVES: We aimed to determine whether supplementation with vitamin D or ω-3 fatty acids remediates pain, changes frequency of pain medication usage, or affects quality of life in young women with endometriosis. METHODS: Women (aged 12-25 y) with surgically confirmed endometriosis and pelvic pain enrolled in a double-blind, randomized, placebo-controlled trial. The primary outcome was pain measured by the visual analog scale (VAS). Secondary outcomes were quality of life, pain catastrophizing, and pain medication usage. Participants were randomly assigned to receive 2000 IU vitamin D3, 1000 mg fish oil, or placebo daily for 6 mo. RESULTS: A total of 147 women were screened and 69 were randomly assigned as follows: 27 to vitamin D3; 20 to fish oil; and 22 to placebo. Participants in the vitamin D arm experienced significant improvement in VAS pain [mean (95% CI) worst pain in the past month, from baseline to 6 mo: 7.0 (6.2, 7.8) to 5.5 (4.2, 6.8), P = 0.02]; however, an improvement of nearly identical magnitude was observed in the placebo arm [6.0 (5.1, 6.9) to 4.4 (3.0, 5.8), P = 0.07]. A more modest improvement was observed in the fish oil arm [5.9 (4.8, 7.0) to 5.2 (3.7, 6.8), P = 0.39]. Neither of the intervention arms were statistically different from placebo. CONCLUSIONS: In young women with endometriosis, supplementation with vitamin D led to significant changes in pelvic pain; however, these were similar in magnitude to placebo. Supplementation with fish oil resulted in about half of the VAS pain reduction of the other 2 arms. Studies are needed to better define the physiology underlying the observed reduction in pain score in the placebo arm that persisted across 6 mo.This trial was registered at clinicaltrials.gov as NCT02387931.

Pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion.

PURPOSE: To investigate the relation between pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion (SAB). METHODS: Our prospective cohort study included 15,590 pregnancies from 11,072 women with no history of SAB in the Nurses' Health Study II (1991-2009). Beverage intake was assessed every 4 years using a validated questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously at <20 weeks gestation. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the relative risks (RRs) and 95 % confidence intervals (CIs). RESULTS: There was a positive linear trend across categories of pre-pregnancy caffeine intake and risk of SAB such that women consuming >400 mg/day had 1.11 (95 % CI 0.98, 1.25) times the risk of SAB compared to women consuming <50 mg/day (p trend = 0.05). Total coffee intake had a positive, linear association with SAB. Compared to women with no pre-pregnancy coffee intake, women consuming ≥4 servings/day had a 20 % (6, 36 %) increased risk of SAB (p trend = 0.01). There was no difference in the association between caffeinated and decaffeinated coffee and risk of SAB. Pre-pregnancy intake of caffeinated tea, caffeinated soda, and decaffeinated soda had no association with SAB. CONCLUSIONS: Pre-pregnancy coffee consumption at levels ≥4 servings/day is associated with increased risk of SAB, particularly at weeks 8-19.

Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth.

OBJECTIVE: To evaluate prospectively the relationship between prepregnancy folate intake and risk of spontaneous abortion and stillbirth. METHODS: Women in the Nurses' Health Study II who self-reported a pregnancy between 1992 and 2009 were included in this analysis. Dietary folate and supplement use was assessed every 4 years, starting in 1991, by a food frequency questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously (spontaneous abortion less than 20 weeks of gestation and stillbirth 20+ weeks of gestation) and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. RESULTS: Among the 11,072 women, 15,950 pregnancies were reported of which 2,756 (17.3%) ended in spontaneous abortion and 120 (0.8%) ended in stillbirth. Compared with women in the lowest quintile of prepregnancy folate intake (less than 285 micrograms/d), those in the highest quintile (greater than 851 micrograms/d) had a relative risk of spontaneous abortion of 0.91 (95% confidence interval [CI] 0.82-1.02) after multivariable adjustment (P trend=.04). This association was primarily attributable to intake of folate from supplements. Compared with women without supplemental folate intake (0 micrograms/d), those in the highest category (greater than 730 micrograms/d) had a relative risk of spontaneous abortion of 0.80 (95% CI 0.71-0.90) after multivariable adjustment (P trend <.001). The association of prepregnancy supplemental folate with risk of spontaneous abortion was consistent across gestational period of loss. A similar inverse trend was observed with the risk of stillbirth, which fell short of conventional significance (P trend=.06). CONCLUSIONS: Higher intake of folate from supplements was associated with reduced risk of spontaneous abortion. Women at risk of pregnancy should use supplemental folate for neural tube defect prevention and because it may decrease the risk of spontaneous abortion. LEVEL OF EVIDENCE: : II.

A prospective cohort study of Vitamins B, C, E, and multivitamin intake and endometriosis.

PURPOSE: Diet is a potentially modifiable risk factor for endometriosis. It has been hypothesized that vitamins C, E, and the B vitamins may influence factors involved in the pathogenesis of endometriosis, such as oxidative stress and steroid hormone metabolism. In this large, prospective cohort study, we examined the relation between intake of vitamins C, E, the B vitamins, and the use of multivitamin supplements and diagnosis of endometriosis. METHODS: Data were collected from women in the Nurses' Health Study II between 1991 and 2005. Diet was assessed via food frequency questionnaire. Incidence rate ratios (RR) and 95% confidence intervals (CI) were estimated using time-varying Cox proportional hazards models. RESULTS: A total of 1383 incident cases of laparoscopically-confirmed endometriosis were observed among 70,617 women during 735,286 person years of follow-up. Intakes of thiamine (B1) (RR = 0.84, CI = 0.72-0.99; P-value, test for linear trend [P] = 0.04), folate (B9) (RR = 0.79, CI = 0.66-0.93; P = 0.003), vitamin C (RR = 0.81, CI = 0.68-0.95; P = 0.02), and vitamin E (RR = 0.70, CI = 0.59-0.83; P<0.0001) solely from food sources were inversely related to endometriosis diagnosis. However, intakes of these nutrients from supplements alone were unrelated to endometriosis. CONCLUSION: Thiamine, folate, vitamin C, and vitamin E from food sources are inversely related to endometriosis risk. Our results suggest that the protective mechanism may not be related to the nutrients themselves but rather other components of foods rich in these micronutrients or factors correlated with diets high in these vitamin-rich foods.

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.

Relationship between caffeine intake and plasma sex hormone concentrations in premenopausal and postmenopausal women.

BACKGROUND: Circulating estrogens and androgens are important factors in the development of various female cancers. Caffeine intake may decrease risk of breast and ovarian cancer, although the data are not entirely consistent. Whether or not caffeine affects cancer risk by altering sex hormone levels is currently unknown. METHODS: We examined the relationship of caffeine, coffee, decaffeinated coffee, and tea with plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone-binding globulin (SHBG) in 524 premenopausal and 713 postmenopausal women from the Nurses' Health Study (NHS) and NHSII. RESULTS: In premenopausal women, caffeine intake was inversely associated with luteal total and free estradiol, and positively associated with luteal progesterone levels (P-trend = .02, .01, .03, respectively). Coffee intake was significantly associated with lower luteal total and free estradiol levels, but not luteal progesterone levels (P-trend = .007, .004, .20, respectively). Among the postmenopausal women, there was a positive association between caffeine and coffee intake and SHBG levels (P-trend = .03 and .06, respectively). No significant associations were detected with the other hormones. CONCLUSIONS: Data from this cross-sectional study suggest that caffeine may alter circulating levels of luteal estrogens and SHBG, representing possible mechanisms by which coffee or caffeine may be associated with pre- and postmenopausal malignancies, respectively. Future studies evaluating how caffeine-mediated alterations in sex hormones and binding protein levels affect the risk of female cancers are warranted.

Lycopene and other carotenoid intake in relation to risk of uterine leiomyomata.

OBJECTIVE: Carotenoids have antioxidant properties and have been associated with reduced risks of some cancers. We hypothesized that carotenoid intake may reduce the risk of diagnosed uterine leiomyoma (UL). STUDY DESIGN: We evaluated the associations between dietary carotenoids and risk of diagnosed UL in 82,512 premenopausal women aged 26-46 years in 1991 in the Nurses' Health Study II over 10 years of follow-up. Diet was assessed every 4 years with a validated food frequency questionnaire, and incidence of UL was assessed biennially by questionnaire. RESULTS: Total lycopene intake was not associated with diagnosed UL risk. Intake of beta-carotene was associated with slightly increased risks of diagnosed UL; this association was restricted to current smokers (for highest vs lowest quintile, relative risk = 1.36, 95% confidence interval 1.05 to 1.76; P(trend) = .003). CONCLUSION: Overall, our findings do not suggest that carotenoids reduce the risk of diagnosed UL. Among current smokers, high intake of beta-carotene may slightly increase risk of diagnosed UL.

Fumonisins disrupt sphingolipid metabolism, folate transport, and neural tube development in embryo culture and in vivo: a potential risk factor for human neural tube defects among populations consuming fumonisin-contaminated maize.

Fumonisins are a family of toxic and carcinogenic mycotoxins produced by Fusarium verticillioides (formerly Fusarium moniliforme), a common fungal contaminant of maize. Fumonisins inhibit ceramide synthase, causing accumulation of bioactive intermediates of sphingolipid metabolism (sphinganine and other sphingoid bases and derivatives) as well as depletion of complex sphingolipids, which interferes with the function of some membrane proteins, including the folate-binding protein (human folate receptor alpha). Fumonisin causes neural tube and craniofacial defects in mouse embryos in culture. Many of these effects are prevented by supplemental folic acid. Recent studies in LMBc mice found that fumonisin exposure in utero increases the frequency of developmental defects and administration of folate or a complex sphingolipid is preventive. High incidences of neural tube defects (NTD) occur in some regions of the world where substantial consumption of fumonisins has been documented or plausibly suggested (Guatemala, South Africa, and China); furthermore, a recent study of NTD in border counties of Texas found a significant association between NTD and consumption of tortillas during the first trimester. Hence, we propose that fumonisins are potential risk factors for NTD, craniofacial anomalies, and other birth defects arising from neural crest cells because of their apparent interference with folate utilization.