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Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow‐up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri‐menopausal women, 111 in post‐menopausal women, and 70 in men) and 706 cancer‐free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre‐menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96–2.92, ptrend =.06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96–3.30, ptrend =.06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28–1.05, ptrend =.07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post‐menopausal women and men but may suggest an involvement of altered sex steroid production in pre‐menopausal women. [ABSTRACT FROM AUTHOR]

Background: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose–response relations based on time‐varying exposures. Objectives: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. Method: We used data from the E3N cohort study of French women (follow‐up, 2004–2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case‐control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time‐varying multivariable Cox proportional hazards regression models to examine the statins–PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. Results: The case‐control study (693 cases, 13,784 controls) showed differences in case‐control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54–79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67–1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51–0.98), with a dose–response relation for the mean daily dose (P‐linear trend = 0.02). There was no association for hydrophilic statins. Conclusion: Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose–response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Results regarding the association between hormonal exposure and risk of Parkinson's disease (PD) are heterogeneous. Objectives: To investigate the association of reproductive life characteristics with PD among postmenopausal women. Methods: The PARTAGE case–control included 130 female cases and 255 age‐matched female controls. Information on gynecological history was obtained from a standardized questionnaire and PD was validated by neurological examination. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression. Results: After adjustment for education level, smoking status, professional exposure to pesticides, and coffee and alcohol drinking, bilateral oophorectomy (OR = 3.55, 95%CI = 1.75–7.20), but neither menopause before age 50 years (OR = 1.24, 95%CI = 0.74–2.09) nor hormone therapy (HT; OR = 1.07, 95%CI = 0.62–1.86), was associated with PD. Conclusion: Our findings suggest that bilateral oophorectomy is associated with increased risk of PD. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: The associations of reproductive history and motor function are controversial. DESIGN: Prospective cohort study with 10 years of follow‐up. SETTING: Three French cities between 1999 and 2011. PARTICIPANTS: A total of 3043 community‐dwelling women from the Three‐City Dijon study population. MEASUREMENTS: We examined the cross‐sectional and longitudinal association of age at menopause, artificial menopause, and parity with walking speed (WS) using linear regression and linear mixed models, respectively. Cox proportional models were used to examine the association of characteristics of reproductive life with disability. RESULTS: Mean baseline WS was 143.8 cm/s. Artificial menopause was associated with slower WS at baseline (β = −3.29; 95% confidence interval [CI] = −5.83 to −0.74; P =.01). Reproductive life characteristics had no effect on change in WS. Increasing age at menopause was associated with reduced disability risk (hazard ratio [HR] for 5‐year increase = 0.92; 95% CI = 0.87‐0.99; P =.02), while parity increased disability risk (HR for ≥3 vs 0 children = 1.53; 95% CI = 1.22‐1.93; P <.01). CONCLUSION: These findings show that early age at menopause and higher parity have a deleterious effect on motor function that persists in older people. J Am Geriatr Soc 68:585–594, 2020 [ABSTRACT FROM AUTHOR]

Background: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined.Methods: This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety.Results: Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels.Conclusions: Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels. [ABSTRACT FROM AUTHOR]

Abstract: Context: Although endogenous oestradiol, generally considered as the female hormone, has been little investigated in men, it could play a role in men's health, mortality in particular. The influence of oestrogen receptors (ER) genetic polymorphisms on this relationship has never been studied. Design and Participants: The Three‐City cohort study included (1999‐2001) 3650 men ≥65 years who were followed for mortality over 12 years. At baseline, total oestradiol (tE2) was measured and ER genotyped in a random subsample of 472 men without hormonal treatment. Free oestradiol (fE2) was estimated using Vermeulen and Södergard algorithms. Main Outcome: Mortality data were obtained from death certificates. We used inverse probability weighted Cox models to examine the association of oestradiol with all‐cause and cause‐specific mortality and its interaction with ER genetic polymorphisms. Results: A total of 183 men died over the follow‐up (cardiovascular disease (CVD), n = 44; cancer, n = 57; other causes, n = 82). After adjustment, there was a quadratic relationship of all‐cause mortality with tE2 and fE2 (P‐quadratic = 0.04 and 0.05, respectively), with higher mortality for the top and bottom tertiles compared to the middle one. These associations were stronger for CVD mortality (P‐quadratic = 0.01 and 0.02 for tE2 and fE2, respectively) and disappeared for cancer mortality. There was no evidence of an interaction of oestradiol with any ER polymorphisms on all‐cause mortality. Conclusion: In elderly men, we showed a nonlinear association of tE2 and fE2 with all‐cause mortality. These quadratic relationships were stronger for CVD mortality and did not exist for cancer mortality. ER genetic polymorphisms did not modify this association. [ABSTRACT FROM AUTHOR]

Background Plasma fibrinogen is a strong predictor of ischaemic arterial disease in women. Sex steroid hormones including hormone therapy may play an important role in the development of cardiovascular disease. However, whether endogenous sex steroid hormones influence the plasma fibrinogen concentrations among postmenopausal women remains unclear. Objectives To investigate the association of plasma fibrinogen levels with endogenous sex steroid hormones and sex hormone binding globulin ( SHBG) among postmenopausal women. Methods We used data from the French prospective Three-City cohort study that included 9294 noninstitutionalized men and women over 65 years of age. Total 17β-oestradiol ( E2, pg/ml), total testosterone ( T, ng/ml), SHBG (n m) and fibrinogen (g/l) were measured in stored plasmas in a subcohort of 602 randomly selected postmenopausal women who used neither hormone medication nor anticoagulation therapy. Multivariate linear regression models were used to estimate the regression coefficients assessed in fibrinogen unit by 1 SD increase in log-distribution of sex steroid hormones and SHBG. Results E2 but neither T nor SHBG was positively associated with plasma fibrinogen levels (β = 0·148, P < 0·001). Adjustment for cardiovascular risk factors including diabetes made no substantial change to the results (β = 0·145, P < 0·001). The association of fibrinogen with E2 was stronger among women with body mass index over 25 kg/m2 compared with those with normal weight (β = 0·156, P < 0·001 and β = 0·092, P = 0·02, respectively, P for interaction = 0·04). Conclusion E2 emerges as a positive and independent correlate of plasma fibrinogen among postmenopausal women, especially in subjects who are overweight. These findings suggest a deleterious effect of endogenous oestrogens on cardiovascular risk profile among postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Despite evidence that estrogens may be involved in atherothrombosis, the role of endogenous sex steroid hormones in ischemic arterial disease among postmenopausal women remains uncertain., Methods and Results: In the Three-City prospective cohort study of subjects (n=9294) >65 years of age, we investigated the association of total 17β-estradiol, bioavailable 17β-estradiol, and total testosterone with the 4-year incidence of ischemic arterial disease among postmenopausal women who did not use any hormone therapy. We designed a case-cohort study including a random sample of 537 subjects and 106 incident cases of first cardiovascular events. Weighted Cox proportional-hazards models with age as the time scale were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for ischemic arterial disease by a 1-standard deviation increase in sex steroid hormones. In univariate analysis, HR of ischemic arterial disease was positively and significantly associated with both total and bioavailable estradiol levels. These associations remained significant after adjustment for traditional cardiovascular risk factors, including body mass index, diabetes, hypercholesterolemia, hypertension, and smoking status (HR: 1.42, 95% CI: 1.12-1.79, P<0.01; and HR: 1.42, 95% CI: 1.12-1.78, P<0.01, respectively). Separate analysis for coronary heart disease yielded similar results (adjusted HR: 1.49, 95% CI: 1.10-2.02, P=0.01; and adjusted HR: 1.50, 95% CI: 1.11-2.04, P<0.01, respectively), and a borderline significant trend was observed for ischemic stroke (HR: 1.34, 95% CI: 0.95-1.89, P=0.08; and HR: 1.32, 95% CI: 0.94-1.84, P=0.11, respectively). By contrast, no significant association was found between total testosterone and ischemic arterial disease in both univariate and adjusted analyses., Conclusions: High plasma level of endogenous estradiol emerges as a new predictor of ischemic arterial disease in older postmenopausal women. (J Am Heart Assoc. 2012;1:e001388 doi: 10.1161/JAHA.112.001388.).