[Additional non-contraceptive effects of contraception: CNGOF Contraception Guidelines]. / Bénéfices non contraceptifs des contraceptions. RPC Contraception CNGOF.

Hormonal and intrauterine contraceptive methods provide women with highly efficient protection against undesired pregnancy. Additional non-contraceptive effects are now well documented. Combined hormonal contraceptives use, either through the oral transdermal and vaginal route, allow a reduction in menorrhagia, dysmenorrhea, functional ovarian cysts, benign breast and uterine disease, endometriosis-related pain and recurrence. A reduction in ovarian cancer risks, including in women with BRCA syndrome, endometrial and colon cancer is documented. This effect is prolonged for years after contraception discontinuation. Non-contraceptive benefits of progestin-only contraceptives are less documented. Use of the levonorgestrel IUD is associated with a reduction in menorrhagia, dysmenorrhea including in case of endometriosis. Copper IUD use is associated with a decrease in cervix and endometrial cancer risk.

Associations among body size across the life course, adult height and endometriosis.

STUDY QUESTION: Are body size across the life course and adult height associated with endometriosis? SUMMARY ANSWER: Endometriosis is associated with lean body size during childhood, adolescence and adulthood; tall total adult height; and tall sitting height. WHAT IS KNOWN ALREADY: The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis. STUDY DESIGN, SIZE, DURATION: We used a nested case-control design within E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale), a prospective cohort of French women. Data were updated every 2-3 years through self-administered questionnaires. Odds ratios (ORs) and 95% CIs were computed using logistic regression models adjusted for a priori confounding factors. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 2416 endometriosis cases were reported as surgically ascertained among the 61 208 included women. MAIN RESULTS AND THE ROLE OF CHANCE: The odds of endometriosis were lower among women who reported having a large versus lean body size at 8 years (P for trend = 0.003), at menarche (P for trend < 0.0001) and at ages 20-25 years (P for trend < 0.0001). Women in the highest quartiles of height had statistically significantly increased odds of endometriosis compared to those in the lowest (<158 cm) (162-164 cm: OR = 1.28, 95% CI = 1.12-1.46; ≥165 cm: OR = 1.33, 95% CI = 1.18-1.49, P for trend < 0.0001). Statistically significantly increased odds were also observed among women with a taller sitting height (OR = 1.24, 95% CI = 1.05-1.47, P for trend = 0.01). Leg length was not statistically significantly associated with endometriosis. LIMITATIONS REASONS FOR CAUTION: Endometriosis cases may be prone to misclassification; however, we restricted our case definition to surgically-confirmed cases, which showed a high validation rate. Body size is based on retrospective self-report, which may be subject to recall bias. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study suggest that endometriosis is positively associated with lean body size across the life course and total adult height. They also suggest that components of height are associated with endometriosis, which should be investigated further. STUDY FUNDING/COMPETING INTEREST(S): The Mutuelle Générale de l'Education Nationale (MGEN); the European Community; the French League against Cancer (LNCC); Gustave Roussy; the French Institute of Health and Medical Research (Inserm). L.V.F. was supported by a T32 grant (#HD060454) in reproductive, perinatal and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (3R25CA057711) National Institutes of Health. M.K. was supported by a Marie Curie Fellowship within the seventh European Community Framework Programme (#PIOF-GA-2011-302078). The authors have no conflicts of interest to declare.

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort.

PURPOSE: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. METHODS: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. RESULTS: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %. CONCLUSIONS: Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size.

Hip circumference is associated with the risk of premenopausal ER-/PR- breast cancer.

OBJECTIVE: We evaluated the relationship between hip and waist circumferences (HCs, WCs), waist-to-hip ratio, height, weight and body mass index (BMI) and breast cancer risk according to menopausal status of women and cancer hormone receptor status. DESIGN: We used data from the French E3N longitudinal prospective cohort. SUBJECTS: In the total population of 63 726 women who were analyzed, 1887 breast cancer cases were diagnosed during follow-up. RESULTS: Among postmenopausal women, the risk of ER+/PR+ breast cancer increased with increasing weight, BMI, and both HCs and WCs, although these two associations disappeared after adjustment for BMI. No association was seen with ER-/PR- breast cancers. Among premenopausal women, among the different factors studied, HC only (no association was observed for any of the different factors studied except for HC) was associated with an increased risk of ER+/PR+ breast cancer after adjustment for BMI (hazard ratio (HR)=1.65; (1.04-2.62) when comparing the highest to lowest tertile; P-trend across tertiles=0.03) and of ER-/PR- breast cancer both before and after adjustment for BMI (HR=2.85 (1.33-6.13); P-trend <0.01, and HR=3.13 (1.19-8.27) P-trend =0.02, respectively). In the latter group, the association with HC was observed whatever the WC (HR=2.81 (1.18-6.70) and HR=2.79 (1.16-6.76) in women with high HC/low WC and high HC/high WC, respectively). CONCLUSION: The increase in risk of premenopausal breast cancer associated with large HC for both ER+/PR+ and ER-/PR- subtypes may provide insight into a specific risk factor for premenopausal breast cancer.

[Characteristics and determinants of initiation of premenopausal use of oral progestagens in the French E3N cohort]. / Caractéristiques et déterminants de l'initiation d'un traitement progestatif oral dans la cohorte française E3N.

OBJECTIVE: To describe the characteristics and determinants of initiation of use of progestagens alone - i.e. without concomitant use of estrogen - among French premenopausal women. METHODS: Forty-one thousand six hundred and three women from the French E3N cohort were included in our analyses. Prevalence of use was calculated from 1992 to 2005. Determinants of progestagens alone initiation were investigated prospectively from 1992 to 2005, using multivariable Cox proportional hazards models. RESULTS: Fifty-eight per cent of women who had reached menopause between 1992 and 2005 ever used progestagens alone during their premenopause. Between 1992 and the end of 1990s, the increase in the prevalence of progestagens alone use in our cohort was close to 50%. Initiation of progestagens alone was significantly associated with a high level of education (postgraduate compared to high-school graduate: Hazard ratio [HR]: 1.09 95% confidence interval [CI]: 1.01-1.18), with a normal body mass index (overweight and obese women compared to normal-weight women: HR=0.84, 95% CI: 0.79-0.90 and HR=0.79, 95% CI: 0.69-0.89 respectively), history of gynecological disorders (mastalgia, benign breast disease and benign uterine or ovarian disease [HR=1.38, 95% CI: 1.27-1.49, HR=1.18, 95% CI: 1.13-1.24 and HR=1.60, 95% CI: 1.52-1.68 respectively]) and with recent gynaecological screening (as measured by recently performed mammogram or Pap smear HR=1.11, 95% CI: 1.05-1.17 and HR=1.38, 95% CI: 1.27-1.49 respectively). CONCLUSION: Since, at least in France, use of progestagens alone at premenopause is common, evaluation of its risks and benefits is of public health importance.

Menopausal hormone therapy and new-onset diabetes in the French Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort.

AIMS/HYPOTHESIS: Two US randomised trials found a lower incidence of type 2 diabetes in women treated by menopausal hormone therapy (MHT) with oral conjugated equine oestrogen combined with medroxyprogesterone acetate. The purpose of this study was to evaluate the influence of various MHTs, according to their formulation and route of administration, on new-onset diabetes in a cohort of postmenopausal French women. METHODS: The association between MHT use and new-onset diabetes was investigated by Cox regression analysis in 63,624 postmenopausal women in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N). Cases of diabetes were identified through self-reporting or drug-reimbursement record linkage, and further validated. RESULTS: 1,220 new-onset diabetes cases were validated. We observed a lower risk of new-onset diabetes among women who had ever used MHT (HR 0.82 [95% CI 0.72-0.93]), compared with those who had never used MHT. Adjustment for BMI during follow-up (rather than according to baseline BMI) did not substantially modify this association. An oral route of oestrogen administration was associated with a greater decrease in diabetes risk than a cutaneous route (HR 0.68 [95% CI 0.55-0.85] vs 0.87 [95% CI 0.75-1.00], p for homogeneity = 0.028). We were not able to show significant differences between the progestagens used in combined MHT. CONCLUSIONS/INTERPRETATION: Use of MHT appeared to be associated with a lower risk of new-onset diabetes. This relationship was not mediated by changes in BMI. Further studies are needed to confirm the stronger effect of oral administration of oestrogen compared with cutaneous administration.

Oral progestagens before menopause and breast cancer risk.

We examined the relationship between use of progestagen-only before menopause (except for mini-pills) after the age of 40 and invasive breast cancer risk in 73 664 women from the French E3N cohort study (mean age at start of follow-up, 51.8 years; mean duration of follow-up, 9.1 years). A total of 2390 cases of invasive breast cancer were diagnosed during follow-up. Risk estimates were calculated using the Cox proportional hazard model. Overall, ever use of progestagen before menopause was not significantly associated with risk (relative risk (RR): 1.01, 95% confidence interval: 0.93-1.11). However, we observed a significant increase in risk associated with the duration of use (P-value for trend: 0.012), current use of progestagens for longer than 4.5 years being significantly associated with risk (RR: 1.44, 95% confidence interval: 1.03-2.00). Prolonged use of progestagens after the age of 40 may be associated with an increased risk of breast cancer and the subject needs to be investigated further.

[Post-partum dysthyroidism. Prospective study in a French region (1986-1988)]. / Dysthyroïdies du post-partum. Etude prospective dans une région française (1986-1988).

UNLABELLED: Post-partum thyroiditis' prevalence has not been previously evaluated in France. OBJECTIVE: To study prospectively a cohort of delivered women to evaluate the prevalence of antimicrosomal antibodies and dysthyroidism during the post partum period. DESIGN, PATIENTS AND MEASURES: 400 women were observed 4 to 12 weeks after delivery and evaluated for the presence of a goiter and a measure of antimicrosomal antibodies (AMA) and us TSH. A subgroup of these selected women was then prospectively followed. HLA typing was also performed. RESULTS: 4 to 12 weeks after delivery, a goiter was found in 40 women. 19 women had positive AMA levels. No abnormality in thyroid function was detected during this period. In these selected women, 8 cases of dysthyroidism, mainly hypothyroidism, were diagnosed later on, 3 to 9 months after delivery. One of them became AMA positive during the follow-up, so the AMA prevalence was 5%. HLA DR4 and the hyplo-type HLA A3B7 were more frequent in this selected population. CONCLUSIONS: Post-partum thyroiditis is a rare and benign disease in France. The transient dysthyroidism occurs later than 3 months after delivery, mainly in women with positive AMA (5% of the parturients). HLA DR4 is more often encountered in this thyroid pathology, as already observed in other Caucasian populations.