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The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial.
Soldat-Stanković, V, Popović-Pejičić, S, Stanković, S, Prtina, A, Malešević, G, Bjekić-Macut, J, Livadas, S, Ognjanović, S, Mastorakos, G, Micić, D, et al
Journal of endocrinological investigation. 2022;(3):583-595
Abstract
PURPOSE To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI). METHODS In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment. RESULTS After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p < 0.001), BMI (p = 0.003), body fat mass (p = 0.001), adiponectin (p = 0.020), fasting glucose (p = 0.001), testosterone (p = 0.015), SHBG (p = 0.013), 17OH progesterone (p = 0.008), LH (p = 0.004) and estradiol (p = 0.014). CONCLUSION Our study showed similar effects of MET and MI on BMI, body composition, hormonal profile, metabolism of glucose and insulin, and adiponectin level. The two insulin sensitizers, MET and MI, were useful in reducing BMI and improving body composition without significant differences between the two treatments in PCOS women. TRIAL REGISTRATION ISRCTN13199265. Trial registration date: 14.04.2021. (ISRCTN Registry), retrospectively registered.
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Linking Physical Activity to Breast Cancer via Sex Hormones, Part 1: The Effect of Physical Activity on Sex Steroid Hormones.
Swain, CTV, Drummond, AE, Boing, L, Milne, RL, English, DR, Brown, KA, van Roekel, EH, Dixon-Suen, SC, Lynch, MJ, Moore, MM, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022;(1):16-27
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Abstract
The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorticoids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity-sex hormone-breast cancer pathway. The confirmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer.See related reviews by Lynch et al., p. 11 and Drummond et al., p. 28.
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Does exercise beneficially affect sex hormones when added to hypo-caloric diets in adults with overweight or obesity? A systematic review and meta-analysis of controlled clinical trials.
Mohseni-Takalloo, S, Beigrezaei, S, Yazdanpanah, Z, Rajaie, SH, Soltani, S, Zohrabi, T, Kaviani, M, Forbes, SC, Baker, JS, Salehi-Abargouei, A
European journal of endocrinology. 2022;(2):285-295
Abstract
OBJECTIVE There is no consensus of opinion if exercise beneficially affects sex hormones if added to weight-loss diets. The purpose of this study was to perform a systematic review and meta-analysis of controlled clinical trials to evaluate the effect of adding exercise to a hypo-caloric diet during a weight-loss program, on serum testosterone, estradiol, and sex hormone-binding globulin (SHBG) in adults with overweight/obesity. DESIGN Systematic review and meta-analysis of the literature. METHODS Online databases including PubMed/MEDLINE, EMBASE, Scopus, ISI Web of Science, and Google Scholar were searched up to April 2021. A random-effects model was applied to compare mean changes in sex hormones and SHBG between participants undergoing a hypo-caloric diet with or without exercise. RESULTS In total, 9 eligible clinical trials with 462 participants were included. Out of these, seven, three, and four studies illustrated changes in testosterone, estradiol, and SHBG, respectively. The meta-analysis revealed that exercise had no significant effect on circulating testosterone (WMD = -0.03 nmol/L, 95% CI: -0.11, 0.06, P = 0.51), estradiol (WMD = -0.46 pg/mL, 95% CI: -1.57, 0.65, P = 0.42), and SHBG (WMD = 0.54 nmol/L, 95% CI: -2.63, 3.71, P = 0.74) when added to low-calorie diets. CONCLUSION The addition of exercise to a hypo-caloric diet provided no additional improvement in sex hormone profiles. Further, well-designed randomized controlled trials with longer follow-up periods in both sexes are recommended to confirm and expand the current results.
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Randomized double blind clinical trial evaluating the Ellagic acid effects on insulin resistance, oxidative stress and sex hormones levels in women with polycystic ovarian syndrome.
Kazemi, M, Lalooha, F, Nooshabadi, MR, Dashti, F, Kavianpour, M, Haghighian, HK
Journal of ovarian research. 2021;(1):100
Abstract
OBJECTIVE The design of this study was due to the report of the antioxidant properties of Ellagic acid (EA) for its evaluation on the Insulin resistance (IR), oxidative stress and sex hormones levels in women with polycystic ovarian syndrome (PCOS). METHODS In this randomized, double-blind, placebo-controlled clinical trial, 60 patients were recruited. Patients were randomly allocated consumed a capsule containing 200 mg of EA per day (n = 30) or placebo (n = 30) for 8 weeks. The fasting blood sugar (FBS), insulin, IR, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), total antioxidant capacity (TAC), Malondialdehyde (MDA), C-reactive protein (CRP), Tumor necrosis factor-alpha (TNF-α), sex hormones and anti-mullerian hormone (AMH) were measured at the beginning and end of the study. RESULT At the end of the study, the mean of FBS, insulin, IR, TC, TG, LDL, MDA, CRP, TNF-α, total testosterone, prolactin and AMH were significantly decreased in the intervention group compared to the placebo group (P < 0.05). Also, there was a significant increase in the mean of TAC after supplementation with EA (P < 0.05). At the end of the study, no significant changes were observed in the mean of anthropometric factors, physical activity and food intake (P > 0.05). CONCLUSION EA supplementation can be helpful as a diet supplement in women with PCOS through improvement in insulin resistance. This supplement may be used to reduce metabolic disorders in women. TRIAL REGISTRATION This study was retrospectively (07-07-2019) registered in the Iranian website ( www.irct.ir ) for registration of clinical trials ( IRCT20141025019669N12 ).
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Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis.
Mori, N, Keski-Rahkonen, P, Gicquiau, A, Rinaldi, S, Dimou, N, Harlid, S, Harbs, J, Van Guelpen, B, Aune, D, Cross, AJ, et al
JNCI cancer spectrum. 2021;(6)
Abstract
BACKGROUND Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. METHODS We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. RESULTS In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], P trend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. CONCLUSION Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.
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Sex Bias in Differentiated Thyroid Cancer.
Suteau, V, Munier, M, Briet, C, Rodien, P
International journal of molecular sciences. 2021;(23)
Abstract
Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient's behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated. Estrogens may increase the production of mutagenic molecules in the thyroid cell and favor the proliferation and invasion of tumoral cells by regulating both the thyrocyte enzymatic machinery and the inflammatory process associated with tumor growth. On the other hand, the worse prognosis of thyroid cancer associated with the male gender is poorly explained.
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Bidirectional Interactions between the Menstrual Cycle, Exercise Training, and Macronutrient Intake in Women: A Review.
Rocha-Rodrigues, S, Sousa, M, Lourenço Reis, P, Leão, C, Cardoso-Marinho, B, Massada, M, Afonso, J
Nutrients. 2021;(2)
Abstract
Women have a number of specificities that differentiate them from men. In particular, the role of sex steroid hormones and the menstrual cycle (MC) significantly impact women's physiology. The literature has shown nonlinear relationships between MC, exercise, and nutritional intake. Notably, these relationships are bidirectional and less straightforward than one would suppose. For example, the theoretical implications of the MC's phases on exercise performance do not always translate into relevant practical effects. There is often a disconnect between internal measures (e.g., levels of hormone concentrations) and external performance. Furthermore, it is not entirely clear how nutritional intake varies across the MC's phases and whether these variations impact on exercise performance. Therefore, a thorough review of the existing knowledge could help in framing these complex relationships and potentially contribute to the optimization of exercise prescription and nutritional intake according to the naturally occurring phases of the MC. Throughout this review, an emerging trend is the lack of generalizability and the need to individualize interventions, since the consequences of the MC's phases and their relationships with exercise and nutritional intake seem to vary greatly from person to person. In this sense, average data are probably not relevant and could potentially be misleading.
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Racial differences in body composition and cardiometabolic risk during the menopause transition: a prospective, observational cohort study.
Marlatt, KL, Redman, LM, Beyl, RA, Smith, SR, Champagne, CM, Yi, F, Lovejoy, JC
American journal of obstetrics and gynecology. 2020;(4):365.e1-365.e18
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Abstract
BACKGROUND Obesity disproportionately affects more women than men. The loss of ovarian function during the menopause transition coincides with weight gain, increases in abdominal adiposity, and impaired metabolic health. Racial differences in obesity prevalence that results from the menopause transition are not well understood. OBJECTIVE The purpose of the study was to assess longitudinal changes in body composition and cardiometabolic risk among black and white women during the menopausal transition. STUDY DESIGN In a secondary analysis of a prospective, observational cohort study (the Healthy Transitions study), 161 women ≥43 years old with a body mass index of 20-40 kg/m2 and who had not yet transitioned through menopause were enrolled at Pennington Biomedical Research Center. Women were seen annually for body composition by dual-energy X-ray absorptiometry, for abdominal adipose tissue distribution by computed tomography, for sex steroid hormones, and for cardiometabolic risk factors that include fasting glucose, insulin, and lipids. Surrogate measures of insulin sensitivity were also calculated. RESULTS Ninety-four women (25 black, 69 white) transitioned through menopause and were included within the analyses. At menopause onset, black women weighed more (77.8±3.0 vs 70.8±1.8 kg) and had a higher systolic (125±16 vs 118±14 mm Hg) and diastolic (80±8 vs 74±7 mm Hg) blood pressure compared with white women (all P≤.05). No other differences in body composition, sex steroid hormones, or cardiometabolic risk factors were observed at menopause onset. Before menopause, white women gained significant weight (3 kg), total body adiposity (6% percent body fat, 9% fat mass, 12% trunk fat mass) and abdominal adipose tissue (19% subcutaneous fat, 15% visceral fat, 19% total adipose tissue), which coincided with significant decreases in estradiol, sex hormone-binding globulin, and estrone sulfate and increases in follicle-stimulating hormone, total cholesterol, and low-density lipoprotein cholesterol. Conversely, black women had more abdominal adipose tissue before menopause, which was maintained across the menopause transition. Black women also had significant decreases in estrone sulfate and total testosterone and increases in follicle-stimulating hormone before menopause. In the postmenopausal years, abdominal subcutaneous adipose tissue, total adipose tissue, follicle-stimulating hormone, total cholesterol, and low-density and high-density lipoprotein cholesterol increased only in white women. CONCLUSION White women gained more abdominal adiposity during the menopause transition compared with black women, which, in part, may be due to differences in the pattern of sex steroid hormone changes between women of different racial backgrounds. The gains in abdominal adiposity in white women were observed in tandem with increased cardiometabolic risk factors. Future studies should consider comprehensive lifestyle approaches to target these increased gains in abdominal adiposity (ie, nutrition and physical activity coaching), while taking into account the potential interactions of race, body adiposity, sex steroid hormones, and their influence on cardiometabolic risk.
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Active steroid hormone synthesis renders adrenocortical cells highly susceptible to type II ferroptosis induction.
Weigand, I, Schreiner, J, Röhrig, F, Sun, N, Landwehr, LS, Urlaub, H, Kendl, S, Kiseljak-Vassiliades, K, Wierman, ME, Angeli, JPF, et al
Cell death & disease. 2020;(3):192
Abstract
Conditions of impaired adrenal function and tissue destruction, such as in Addison's disease, and treatment resistance of adrenocortical carcinoma (ACC) necessitate improved understanding of the pathophysiology of adrenal cell death. Due to relevant oxidative processes in the adrenal cortex, our study investigated the role of ferroptosis, an iron-dependent cell death mechanism and found high adrenocortical expression of glutathione peroxidase 4 (GPX4) and long-chain-fatty-acid CoA ligase 4 (ACSL4) genes, key factors in the initiation of ferroptosis. By applying MALDI mass spectrometry imaging to normal and neoplastic adrenocortical tissue, we detected high abundance of arachidonic and adrenic acid, two long chain polyunsaturated fatty acids which undergo peroxidation during ferroptosis. In three available adrenal cortex cell models (H295R, CU-ACC1 and CU-ACC-2) a high susceptibility to GPX4 inhibition with RSL3 was documented with EC50 values of 5.7 × 10-8, 8.1 × 10-7 and 2.1 × 10-8 M, respectively, while all non-steroidogenic cells were significantly less sensitive. Complete block of GPX4 activity by RSL3 led to ferroptosis which was completely reversed in adrenal cortex cells by inhibition of steroidogenesis with ketoconazole but not by blocking the final step of cortisol synthesis with metyrapone. Mitotane, the only approved drug for ACC did not induce ferroptosis, despite strong induction of lipid peroxidation in ACC cells. Together, this report is the first to demonstrate extraordinary sensitivity of adrenal cortex cells to ferroptosis dependent on their active steroid synthetic pathways. Mitotane does not induce this form of cell death in ACC cells.
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[Acupuncture ameliorates negative emotion in PCOS patients: a randomized controlled trial].
Zhang, HL, Huo, ZJ, Wang, HN, Wang, W, Chang, CQ, Shi, L, Li, D, Li, R, Qiao, J
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2020;(4):385-90
Abstract
OBJECTIVE To evaluate the effectiveness and possible mechanism of acupuncture treatment for negative emotion in patients with polycystic ovary syndrome (PCOS). METHODS A total of 40 PCOS patients were randomly divided into an observation group and a control group, 20 cases in each one. Both groups received lifestyle interventions (exercise and diet guidance) on the 5th day of menstruation. On the basis of above treatment, the patients in the observation group received acupuncture at Guanyuan (CV 4), Zhongwan (CV 12), Guilai (ST 29), Futu (ST 32), Liangqiu (ST 34), Sanyinjiao (SP 6), Zusanli (ST 36), Hegu (LI 4), Shenmen (HT 7), Baihui (GV 20) as the main acupoints, and connected the electroacupuncture (continuous wave, 2 Hz, 30 min), once every other day, 3 times a week. The treatment for 1 month was as one course and 4 courses were required totally in both groups. Before and after treatment, the body mass index (BMI), ferriman-gallway (F-G) score, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score, PCOS health-related quality of life questionnaire (PCOSQ) score were observed, meanwhile, serum sex hormone, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progestin (P), prolactin (PRL), testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) levels, and serumβ-endorphin levels were detected. RESULTS Compared with before treatment, the BMI, F-G score, SAS score, SDS score and serum FAI level were decreased and the PCOSQ score and the levels of serum SHBG andβ-endorphin were increased in the observation group after treatment (all P<0.05). Compared with before treatment, the SDS score was decreased in the control group after treatment (P<0.05). Compared with the control group, the F-G score, SDS score, SAS score, and serum FAI level were lower, and the PCOSQ score and serumβ-endorphin level were higher in the observation group after treatment (all P<0.05). CONCLUSION Applying acupuncture to the treatment of patients with PCOS can effectively relieve anxiety and depression, and the mechanism may be related to the regulation on the levels of serumβ-endorphin and androgen.