Sylvie Dodin

Organochlorine exposure and the risk of endometriosis

OBJECTIVE To compare mean concentrations of organochlorine in women with a new diagnosis of endometriosis and in controls. DESIGN Case-control study. SETTING Women attending an institutional clinic of reproductive endocrinology. PATIENT(S) Cases and controls were selected among women who underwent laparoscopy for chronic pelvic pain, infertility, or tubal fulguration between January 1994 and December 1994. Eighty-six women with endometriosis and 70 controls, matched for the indication for laparoscopy, were recruited. MAIN OUTCOME MEASURE(S) Mean organochlorine plasma concentrations of 14 polychlorinated biphenyl congeners and 11 chlorinated pesticides were compared between the cases and controls. Analysis of covariance was used to adjust means for confounding variables, and odds ratios were estimated by logistic regression. RESULT(S) Crude geometric mean concentrations did not differ significantly between cases and controls for any of the organochlorine compounds. Similarly, crude or adjusted means of the sum of polychlorinated biphenyl congeners, the sum of chlordanes, or the sum of dichlorodiphenyltrichloroethanes did not differ between the groups. There was no significant linear trend in the adjusted odds ratios for endometriosis as organochlorine concentrations increased. CONCLUSION(S) These results suggest that exposure to polychlorinated biphenyls and chlorinated pesticides during adulthood is not associated with endometriosis in the general population.

Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women

OBJECTIVE To assess serum lipid changes by a phytoestrogen dietary supplement compared with oral estrogen‐progesterone replacement in hypercholesterolemic menopausal women. METHODS Twenty‐five menopausal patients with total cholesterol greater than 6.2 mmol/L (240 mg/dL), a cholesterol/high‐density lipoprotein‐cholesterol ratio greater than 4.5 and triglycerides less than 3.5 mmol/L (310 mg/dL) after a 4‐month diet, were randomized to add 40 g/day of crushed flaxseed to their diet or to take daily 0.625 mg of conjugated equine estrogens alone (hysterectomy, n = 10) or combined with 100 mg of micronized progesterone (intact uterus, n = 15). After 2 months of treatment, both groups continued the diet alone during a 2‐month washout period before crossing over to the alternate treatment for 2 more months. RESULTS Differences were found between hormone replacement therapy and flaxseed respectively for decrease of low‐density lipoprotein cholesterol (3.8 ± 0.2 versus 4.4 ± 0.2 mmol/L) (148 ± 8 versus 170 ± 8 mg/dL) (P = .10), increase of high‐density lipoprotein cholesterol (1.6 ± 0.04 versus 1.3 ± 0.03 mmol/L) (62 ± 1 versus 50 ± 1 mg/dL) (P = .001), and increase of apolipoprotein A‐1 (1.71 ± 0.07 versus 1.42 ± 0.05 g/L) (P = .003). These changes were not related to modifications in diet, exercise, or anthropometric measurements evaluated in parallel. Both treatments produced similar decreases in menopausal symptoms and in glucose and insulin levels. Only hormone replacement therapy as compared with flaxseed induced an elevation of sex hormone binding globulin (P = .004), lowered fibrinogen (P = .08), and plasminogen activator inhibitor type 1 (P = .01). CONCLUSION Although 40 g of flaxseed is as effective as oral estrogen‐progesterone to improve mild menopausal symptoms and to lower glucose and insulin levels, only hormone replacement therapy significantly improves cholesterol profile in hypercholesterolemic women and favorably modifies markers related to cardiovascular health.

Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial

BACKGROUND Psychological distress (PD) and depressive symptoms are commonly observed during menopausal transition. Studies suggest that omega-3 (n-3) fatty acids may help alleviate depression. OBJECTIVE The objective was to compare enriched ethyl-eicosapentaenoic acid (E-EPA) supplementation with placebo for the treatment of PD and depressive symptoms in middle-aged women. DESIGN Women with moderate-to-severe PD (n = 120) were randomly assigned to receive 1.05 g E-EPA/d plus 0.15 g ethyl-docosahexaenoic acid/d (n = 59) or placebo (n = 61) for 8 wk. The main outcomes were 8-wk changes in PD scores [Psychological General Well-Being Schedule (PGWB)] and depressive scales [20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the 21-item Hamilton Depression Rating Scale (HAM-D-21)]. RESULTS At baseline, women with PD were mildly to moderately depressed, and 24% met the major depressive episode (MDE) criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. After 8 wk, outcomes improved in both groups, but no significant differences were noted between them. Stratification analyses for MDE diagnosis at baseline indicated that differences in adjusted 8-wk changes between the E-EPA group without MDE (n = 46) and the placebo group (n = 45) were 8.0 (95% CI: 0.6, 15.3; P = 0.034) for the PGWB, -0.2 (95% CI: -0.01, -0.4; P = 0.040) for the HSCL-D-20, and -2.7 (95% CI: -0.3, -5.1; P = 0.030) for the HAM-D-21. Differences in adjusted 8-wk changes between the E-EPA group with MDE (n = 13) and the placebo group (n = 16) were not significant. CONCLUSIONS To our knowledge, this is the first trial of n-3 supplementation in the treatment of PD and depressive symptoms in middle-aged women. In women with PD without MDE at baseline, the 8-wk changes in PD and depressive scales improved significantly more with E-EPA than with placebo. This trial was registered at http://www.controlled-trials.com as ISRCTN69617477.

Health-At-Every-Size and Eating Behaviors: 1-Year Follow-Up Results of a Size Acceptance Intervention

BACKGROUND Poor long-term success observed with current weight-control strategies stresses the relevance to explore new weight management approaches. OBJECTIVE To assess the effects of a Health-At-Every-Size (HAES) intervention on eating behaviors, appetite sensations, metabolic and anthropometric variables, and physical activity levels in women at 6-month and 1-year postintervention. DESIGN Randomized controlled trial; measurements at baseline, at the end of the intervention period (4 months), and at 6-month and 1-year postintervention (10 months and 16 months, respectively). Intervention and testing took place from September 2003 to August 2006. PARTICIPANTS/SETTING Premenopausal overweight/obese women (n=144; mean age of 42.3+/-5.6 years), recruited from free-living, general community. INTERVENTION Women were randomly assigned to: HAES group (n=48), social support group (n=48), or control group (n=48). MAIN OUTCOME MEASURES Eating behaviors (restraint, disinhibition, and susceptibility to hunger), appetite ratings (desire to eat, hunger, fullness, and prospective food consumption), anthropometric and metabolic variables (body mass index, waist and hip circumferences, blood lipid levels, and blood pressure), and engagement in moderate to intense physical activity (energy cost > or =1.2 k cal x kg(-1) x 15 minutes(-1) [> or =4.8 metabolic equivalents]). STATISTICAL ANALYSES PERFORMED Changes for each dependent variable were assessed by linear mixed models according to a group (HAES vs social support vs control) by time (baseline vs 4 months vs 10 months vs 16 months) split-plot design. RESULTS Situational susceptibility to disinhibition and susceptibility to hunger significantly decreased over time in both HAES group (-0.9+/-0.2 and -1.3+/-0.5, respectively) and the social support group (-0.4+/- 0.2 and -1.4+/-0.5, respectively). Although eating behavior scores observed at 16 months did not differ between HAES and social support groups (situational susceptibility to disinhibition: 2.5+/-0.2 in HAES group vs 2.7 +/- 0.2 in social support group; susceptibility to hunger: 4.2+/-0.5 in both groups), they were lower in these groups than scores noted in the control group (3.3+/-0.2 for situational susceptibility to disinhibition and 5.9+/-0.5 for susceptibility to hunger). CONCLUSIONS These results suggest that, when compared to a control group, an HAES approach could have long-term beneficial effects on eating behaviors related to disinhibition and hunger. In addition, our study did not show distinctive effects of the HAES approach in comparison to a social support intervention.

The Effect of 20 ??g Ethinyl Estradiol/1 mg Norethindrone Acetate (MinestrinTM), a Low-Dose Oral Contraceptive, on Vaginal Bleeding Patterns, Hot Flashes, and Quality of Life in Symptomatic Perimenopausal Women

One hundred and thirty two perimenopausal women with climacteric symptoms participated in a placebo-controlled, double-blind, randomized, parallel group study of the oral contraceptive Minestrin™ containing 20 μg ethinyl estradiol/1 mg norethindrone acetate (EE 20 μg/NA 1 mg). Bleeding patterns, hot flashes, quality of life, and safety were assessed over a 24-week (6 cycle) interval. There was no difference in the average duration of bleeding episodes between the treatment groups, but EE 20 μg/NA 1 mg therapy shortened menstrual cycle duration (p < 0.05), decreased its variability, and markedly lowered bleeding severity (p < 0.01). The incidence and duration of clots/flooding were reduced in the EE 20 μg/NA 1 mg group for the last 3 cycles (p < 0.05). The frequency of inter-menstrual bleeding was higher in the oral contraceptive users during the first 12 weeks (p < 0.05), but no difference was observed between the two groups after 3 months of treatment. The frequency and severity of hot flashes were decreased in the treated group, but statistical significance was not reached due to large variability. Quality of life assessments indicated significant improvements in the oral contraceptive treatment group. Adverse events were similar in occurrence and type in treated and control groups; however, normalization of hematologic parameters and beneficial effects on endometrium were noted more often in the active treatment group. Compared with placebo, EE 20 μg/NA 1 mg improved cycle control, decreased bleeding severity, and improved quality of life while offering a similar safety profile.

The Association Between Heel Ultrasound and Hormone Replacement Therapy Is Modulated by a Two‐Locus Vitamin D and Estrogen Receptor Genotype

Evidence supports the role of estrogen deprivation in the process of bone remodeling and increased risk of fracture in postmenopausal women but little is known about the genetic basis of individual differences in response to therapy. In a cross‐sectional study, 425 ambulatory postmenopausal French‐Canadian women from Quebec (age range, 42–85 years old) were genotyped for a common Bsm I polymorphism at the vitamin D receptor (VDR) gene as well as a Pvu II polymorphism in the estrogen receptor (ESR1) gene. Heel ultrasound was determined by right calcaneal quantitative ultrasound (QUS) and results were expressed as an age‐ and‐weight‐adjusted stiffness index (heel SI z score). Our aim was to investigate the interaction between hormone‐replacement therapy (HRT) and receptor genotypes in an effect on heel SI. Notably, a two‐locus genotype (VDR‐bb/ESR‐PP) present in 9.5% of women was responsible for over 30% of the total HRT‐related heel SI difference in the whole sample. Women bearing this combined VDR/ESR1 genotype who received HRT for more than 5 years had a 21% (1.25 SD) greater heel SI (p = 0.002) than those bearing the same genotype but who received HRT for <5 years. This may translate into a 2‐ to 3‐fold difference in the risk of fracture. Although follow‐up studies are needed, our findings suggest that QUS of the heel in postmenopausal women taking HRT is affected by variation in VDR and ESR1 loci, jointly.

Plasma organochlorine concentrations and bone ultrasound measurements: a cross-sectional study in peri-and postmenopausal Inuit women from Greenland.

BackgroundInuit women are highly exposed through their traditional seafood based diet to organochlorine compounds, some of them displaying endocrine disrupting properties. We hypothesized that this exposure might be related to bone characteristics that are altered in osteoporosis, because hormone deficiency is a known risk factor for the disease.MethodsWe measured quantitative ultrasound parameters (QUS) at the right calcaneum of 153 peri- and postmenopausal Inuit women (49–64 year old) from Nuuk, Greenland, and investigated the relation between these parameters and plasma organochlorine concentrations. We used high-resolution gas chromatography with electron capture detection to analyze plasma samples for 14 polychlorinated biphenyls (PCB) congeners and 11 chlorinated pesticides and metabolites. We analysed morning urine samples for cadmium, a potential confounder, by atomic absorption spectrometry. We used a validated questionnaire to document dietary and lifestyle habits as well as reproductive and medical histories.ResultsConcentrations of PCB 153, a surrogate of exposure to most organochlorines present in plasma samples, were inversely correlated to QUS parameters in univariate analyses (p < 0.001). However, PCB 153 concentrations were not associated with QUS values in multivariate analyses that comprised potential confounding factors such as age, body weight, former oral contraceptive use and current hormone replacement therapy (HRT) use, which were all significant predictors of bone stiffness (total R2 = 0.39; p < 0.001).ConclusionOverall we found little evidence that organochlorines exposure is related to osteoporosis in Greenlandic Inuit women, but the hypothesis that exposure to dioxin-like compounds might be linked to decreased bone quality and osteoporosis deserves further attention.

Sex differences in the impact of the Mediterranean diet on cardiovascular risk profile

The traditional Mediterranean diet (MedDiet) is now widely recommended in the prevention of CVD. However, it is not known whether the MedDiet has the same beneficial cardiovascular effects in women and in men. The objective of the present study was to investigate sex-related differences with regard to changes in cardiometabolic variables in response to a 4-week isoenergetic MedDiet. Participants were thirty-eight men and thirty-two premenopausal women aged between 25 and 50 years who had slightly elevated LDL-cholesterol (LDL-C) concentrations (3·4-4·9 mmol/l) or total cholesterol:HDL-cholesterol ratio ≥ 5·0. A 4-week run-in period preceded the MedDiet in order to control the inter- and intra-individual variability. Cardiometabolic variables were measured before and after the MedDiet. Total cholesterol, LDL-C, apoB and apoA-1 plasma concentrations as well as diastolic blood pressure decreased (P < 0·05) in both men and women (respectively, 10, 10, 10, 6 and 5% for men and 6, 7, 9, 4 and 4% for women). ApoA-2 concentrations and insulin concentrations 2 h after the oral administration of 75 g of glucose demonstrated sex × time interactions (respectively, P = 0·05 and P = 0·03) and only men experienced a decrease for these variables (respectively, 8 and 25%). In conclusion, consuming a MedDiet led to significant changes in plasma lipid profile in both men and women, while only men had significant improvements in insulin homeostasis. These results support the importance of investigating sex-related differences in response to diet in order to perhaps further individualise dietary guidelines in the prevention of CVD and type 2 diabetes.

Clinical efficacy and safety of low‐dose flutamide alone and combined with an oral contraceptive for the treatment of idiopathic hirsutism

BACKGROUND AND OBJECTIVE High doses of flutamide, which is the only antiandrogen that specifically blocks the androgen receptor, have recently been used with good clinical results in women with hirsutism. Since regression of hair growth requires long‐term therapy, clinical and economic considerations are important. The use of the lowest efficacious dosage could reduce costs. This study was undertaken to compare safety and efficacy of a low dose of flutamide (125 mg twice daily) alone and in combination with a triphasic oral contraceptive (OC) in women with idiopathic hirsutism.

A Frequent Regulatory Variant of the Estrogen-Related Receptor α Gene Associated With BMD in French-Canadian Premenopausal Women†

Genes are important BMD determinants. We studied the association of an ESRRA gene functional variant with BMD in 1335 premenopausal women. The ESRRA genotype was an independent predictor of L2‐L4 BMD, with an effect similar to smoking and equivalent to a 10‐kg difference in weight.