High organochlorine body burden in women with estrogen receptor-positive breast cancer.
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Biomedical subjects
Publications and source records attributed to S Dodin.
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OBJECTIVE: We evaluated the effect of sex steroids on the lipid fractions (cholesterol, triglycerides, LDL-C, HLD-C and subfractions HDL2-C and HDL3-C) and on the apolipoproteins (A-1 and B) in relation to age in women. DESIGN: Twenty-eight normally cycling women belonging to three age groups (20-29, n = 11; 30-39, n = 10; 40-49, n = 7) had blood samples taken daily during one cycle. MEASUREMENTS: Serum lipid fractions, apolipoproteins (Apo) and ovarian steroids were measured daily during the menstrual cycle. Diet and exercise were also evaluated. RESULTS: Each age group had comparable profiles for daily serum concentrations of oestradiol, progesterone and testosterone. There were no significant variations of the lipid fractions or of the ApoA-I and ApoB during the menstrual cycle in each group. Using regression analysis, modifications of cholesterol, triglycerides, LDL-C and ApoB were partially but significantly correlated with age. These changes occurred in spite of similar serum concentrations of oestradiol, progesterone and testosterone in the three groups. Lipid fractions were also affected by the increase of body mass index with age, especially HDL-C and HDL2C. However, there were no differences in lipid and energy intake or in energy expenditure during physical leisure activities. CONCLUSIONS: These results indicate that physiological fluctuations of ovarian steroids have no effects on lipids and Apo in normally cycling women of increasing age. In this study, the age related changes in the lipid fractions were partially correlated with body mass index but not with energy intake or exercise.
OBJECTIVE: The evaluation of cholesterol fractions and apoproteins during ovarian suppression by a GnRH agonist implant vs danazol in the treatment of endometriosis. DESIGN: A randomized study in 33 patients comparing goserelin (3.6 mg/4 weeks s.c., n = 20) with danazol (2 x 400 mg/day p.o., n = 13) in patients with a laparoscopic diagnosis of endometriosis and treated for 6 months. MEASUREMENTS: Triglycerides, cholesterol (C), LDL-C, HDL-C subfractions and apoproteins A-1 and B were measured at admission, at months 2, 4 and 6 of treatment and at month 2 post-treatment. RESULTS: After 1 month of therapy, serum oestradiol levels were maintained in the menopausal range with goserelin and in the early follicular phase range with danazol. Goserelin induced a significant elevation in HDL-C (by 31.4%), in HDL2-C (24.6%) and in HDL3-C (45.7%) but no significant change in LDL-C or in ApoA-1 and ApoB. By contrast, danazol caused significant diminutions in HDL-C (23.9%), HDL2-C (56.6%) and ApoA-1 (35.6%). Moreover, danazol increased LDL-C (10.5%) and ApoB (29.0%, P less than 0.05). The lipoprotein changes during goserelin had a favourable effect on the atherogenic index (cholesterol/HDL-C) and ApoA-1/ApoB ratio whereas those of danazol had opposite effects. These changes reverted 2 months after danazol while HDL was still elevated after goserelin. CONCLUSIONS: In relation to cholesterol, goserelin is a safe medication. The significance of temporary adverse changes in cholesterol fractions due to danazol is still unknown.
Before treatment, the trabecular bone mineral content of the lumbar spine and femoral neck was not significantly different between endometriosis patients and age-matched controls (N = 26). In 17 subjects treated with a monthly goserelin implant, serum estradiol (E2) levels were suppressed into the menopausal range. Mean decreases from pre-treatment values in the lumbar spine and femoral neck were -5.7 and -3.8% at 3 months and -8.2 and -7.7% at 6 months of treatment, respectively; lumbar spine values were significantly different (P less than .05) from those of the control group, whose values changed little during the same period. Significant increases over baseline values were also observed in urinary calcium-creatinine ratio and serum alkaline phosphatase. In nine danazol-treated subjects, serum E2 levels were generally within the early follicular-phase range. There were no significant changes in bone assessments. Normal menses returned within 2 months after cessation of either medication. Six months after goserelin treatment, the lumbar spine and femoral neck bone mineral content was still reduced but to values not significantly different from the pre-treatment and control values; urinary calcium-creatinine ratio was decreased, whereas serum alkaline phosphatase was still elevated. The rapid and deep suppression of ovarian steroidogenesis by a monthly goserelin implant induced significant bone loss compared with the control and danazol groups. This loss was not reversed completely 6 months after cessation of treatment, but bone densities at that time were not different from those of controls. Studies of larger numbers of patients followed for longer periods will be required to resolve the question of complete reversibility.