Prenatal Testosterone Exposure Is Linked to Sexually Dimorphic Changes in Body Composition in 7-Year-Old Children.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism. In pregnancy, testosterone levels may be higher in women with PCOS compared with controls. To compare total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) levels in third-trimester pregnant women with PCOS and controls and to establish reference ranges for TT, FT, and SHBG in PCOS and controls. The study was part of the prospective study, Odense Child Cohort. PCOS was diagnosed by questionnaires and/or patient records. Fasting blood samples were collected at gestational week 28 and plasma TT was measured by liquid chromatography-tandem mass spectrometry in women with PCOS (n = 145) and in women without PCOS (controls, n = 1341). Levels of TT (mean, 2.4 vs 2.0 nmol/L) and FT (mean, 0.005 vs 0.004 nmol/L) were higher, whereas SHBG levels (mean, 447 vs 477 nmol/L) were lower in women with PCOS vs controls (all P < 0.001). Reference intervals for TT, FT, and SHBG in women with PCOS and controls were overlapping, and partitioning of reference intervals was an ambiguous decision. In multiple regression analyses, TT and FT levels were positively associated with PCOS status and BMI and inversely associated with age and parity. Offspring sex did not predict maternal TT and FT. TT and FT levels were higher in third-trimester pregnant women with PCOS compared with controls. Separate reference interval for FT in women with PCOS should be considered.

In order to evaluate the role of sex hormones and aging on body composition in males, plasma testosterone, free testosterone, estradiol and sex hormone binding globulin as well as insulin-like growth factor I (IGF-I) and insulin levels were determined in a group of 372 ambulant males, aged 20–85 years. In addition, these parameters were correlated with aging and body composition. Muscle mass decreased and fat mass increased significantly with age. Both age and free testosterone were independent determinants of fat mass. Abdominal fat was by far the most important determinant of free testosterone levels, gluteal fat contributing little to the free testosterone levels. The decrease of fat free mass was essentially correlated with age, the contribution of free testosterone levels being marginal. The ratio of subcutaneous to visceral fat decreased with age, independent of body mass index, free testosterone or estradiol levels. This suggests that, at a similar degree of obesity, the health hazards are more pronounced in elderly men.IGF-I levels correlated negatively with fat mass, but this correlation was lost after adjustment for age. The negative correlation of fat mass with (free) testosterone levels persisted after correction for IGF-I levels, suggesting that the decrease of free testosterone levels is an independent co-determinant of the age-associated increase in fat mass. Hence, it may be concluded that the age-associated decrease in androgen levels plays an important role in the changes in body composition, independent of the effect of age itself or the age-associated decrease in IGF-I levels.

Most of the mothers are very attentitve to changes in body composition, especially postpartum weight loss. One of the factors believed to facilitate the weight loss and body fat loss in postpartum mothers is breastfeeding. Factor that affect the relationship between breastfeeding with maternal postpartum body composition are food intake and physical activity. The aim of this study is to analyze the change in body composition between the mother who give exclusive breastfeeding for 6 months and the mother who don’t and also attempts to analyze the effect of breastfeeding duration to the change in body composition and the factor affecting it.This study used the panel study with longitudinal approach. 32 respondents observed for 6 months. Fat mass measurement data are collected using skinfold caliper and breastfeeding status, food intake and physical actiuvity data are collected using interview. The relationship between breastfeeding with the change in body composition is analyzed using t-test analysis. T-test analysis are also used to test the effect of food intake and physical activity to breastfeeding. Regression analysis are used to analyze the effect of food intake and physical activity to body composition.According to the result of statistical analysis, there is no significance effect of breastfeeding for 6 months to the change in maternal postpartum body composition (fat mass and free fat mass) (p = 0.743; p = 0.771) and also no significance effect of food intake and physical activity to the relation between breastfeeding with the change in body composition. There is a significance effect of breastfeeding for 4 months to the change in the body composition (p = 0.046). The average fat mass change in mother who give exclusive breastfeed is higher than the one who don’t.From 32 respondents in this study, only 4 mothers can successfully give exclusive breastfeed for 6 months. The average fat mass change in mother who give exclusive breastfeed is higher than the one who don’t. There is no significance effect of breastfeeding for 6 months to the change in maternal postpartum body composition (fat mass and free fat mass). There is a significance effect of breastfeeding for 4 months to the change in maternal postpartum body composition.Keywords: Breastfeeding, body composition, maternal postpartum

Are higher testosterone levels during pregnancy in women with polycystic ovary syndrome (PCOS) associated with longer offspring anogenital distance (AGD)? AGD was similar in 3-month-old children born of mothers with PCOS compared to controls. AGD is considered a marker of prenatal androgenization. Maternal testosterone levels were measured by mass spectrometry at Gestational Week 28 in 1127 women. Maternal diagnosis of PCOS before pregnancy was defined according to Rotterdam criteria. Offspring measures included AGD from anus to posterior fourchette (AGDaf) and clitoris (AGDac) in girls and to scrotum (AGDas) and penis (AGDap) and penile width in boys and body composition (weight and BMI SD scores) at age 3months. The study was part of the prospective study, Odense Child Cohort (OCC), and included mothers with PCOS (n = 139) and controls (n = 1422). The control population included women with regular menstrual cycles (<35days) before conception and no signs of androgen excess (hirsutism and/or acne). AGD measures were comparable in offspring of women with PCOS compared to controls (all P > 0.2) despite significantly higher maternal levels of total testosterone (mean: 2.4 versus 2.0nmol/l) and free testosterone (mean: 0.005 versus 0.004nmol/l) in women with PCOS versus controls (both P < 0.001). In women with PCOS, maternal testosterone was an independent positive predictor of offspring AGDas and AGDap in boys. Maternal testosterone levels did not predict AGD in girls born of mothers with PCOS or in boys or girls born of women in the control group. The diagnosis of PCOS was based on retrospective information and questionnaires during pregnancy. Women participating in OCC were more ethnically homogenous, leaner, more educated and less likely to smoke compared to the background population. Our study findings, therefore, need to be reproduced in prospective study cohorts with PCOS, in more obese study populations and in women of other ethnicities. Our finding of the same AGD in girls born of mothers with PCOS compared to controls expands previous results of studies reporting longer AGD in adult women with PCOS. Our results suggest that longer AGD in adult women with PCOS could be the result of increased testosterone levels in puberty, perhaps in combination with weight gain. Financial grants for the study were provided by the Danish Foundation for Scientific Innovation and Technology (09-067180), Ronald McDonald Children Foundation, Odense University Hospital, the Region of Southern Denmark, the Municipality of Odense, the Mental Health Service of the Region of Southern Denmark, The Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (2101-08-0058), Odense Patient data Explorative Network, Novo Nordisk Foundation (grant no. NNF15OC00017734), the Danish Council for Independent Research and the Foundation for research collaboration between Rigshospitalet and Odense University Hospital and the Health Foundation (Helsefonden). There is no conflict of interest of any author that could be perceived as prejudicing the impartiality of the research reported.

Background and Objectives: Sarcopenic obesity, a clinical condition coexisting with obesity and sarcopenia, is associated with a high risk of functional impairment, reduced quality of life, and increased mortality. A decline in age-related free testosterone (FT) levels has been reported to be associated with decreased muscle mass and muscle strength and increased fat mass. However, the association between low FT levels and risk of sarcopenic obesity has not been well studied. This study aimed to investigate the direct association between low FT levels and sarcopenic obesity. Materials and Methods: This cross-sectional study used data of 982 community-dwelling men aged 70-84 years from the Korean Frailty and Aging Cohort Study. Sarcopenia was defined according to the criteria of the Asian Group for Sarcopenia (AWGS) 2019. Obesity was defined as a body fat mass ≥28.3%. Participants who met both sarcopenia and obesity criteria were defined as having sarcopenic obesity. Low FT levels were defined as FT levels <17.35 pmol/L according to the Endocrine Society Clinical Practice Guidelines. Results: The prevalence of sarcopenia, obesity, and sarcopenic obesity was significantly higher in the low-FT group than in the normal-FT group. Low FT levels were significantly associated with a higher risk of obesity (odds ratio [OR], 2.09, 95% confidence interval [CI], 1.11-3.92), sarcopenia (2.57, 95% CI 1.08-6.10), and sarcopenic obesity (3.66, 95% CI 1.58-8.47) compared with the healthy control group. The risk of low appendicular skeletal muscle mass index (ASMI) (1.78, 95% CI 1.04-3.02) and high fat mass (1.92, 95% CI 1.12-3.31) was significantly higher in the low-FT group than in the normal-FT group. Conclusions: This study showed that low FT levels were associated with a higher risk of sarcopenic obesity. Low FT levels were mainly related to body composition parameters such as low ASMI and high fat mass.

Children weight gain is mostly due to fat-free mass than fat mass, but the changes in body composition dynamics related to child growth can be attributed to the obesity epidemic. We aimed to assess changes in measures of body composition from 6 to 11 years of age according to sex, and to examine whether changes in these measures are associated with sociodemographic characteristics. A longitudinal study using data from the 2004 Pelotas Birth Cohort was conducted, and assessed body composition and fat distribution through measures of BMI, fat mass index, fat-free mass index, and android and gynoid fat mass percentages from DXA. Changes in body fatness were calculated as the difference between measures collected at 6 and 11 years of age, and linear regression models were used to assess changes in body composition according to sociodemographic characteristics. An increase in mean BMI z-score from 6 to 11 years was observed only in boys and obesity prevalence reached one out of four boys and one out of five girls. There was an increase in fat mass percentage, fat mass index and android fat mass, with this effect more accentuated in boys when compared to girls. Maternal BMI was the most consistent factor associated with change in body fatness. Children from mothers with obesity showed larger increases in fat mass percentage, fat mass index and android fat mass. There was an increase in body fatness and a centralisation of body shape, mostly associated with male sex and maternal obesity. These results may indicate an early risk of non-communicable diseases in children from the Pelotas 2004 Birth Cohort.

Both baseline cardiorespiratory fitness and adiposity predict the risk of cancer mortality. However, the effects of changes in these two factors over time have not been evaluated thoroughly. The aim of this study was to examine the independent and joint associations of changes in cardiorespiratory fitness and body composition on cancer mortality. The cohort consisted of 13,930 men (initially cancer-free) with two or more medical examinations from 1974 to 2002. Cardiorespiratory fitness was assessed by a maximal treadmill exercise test, and body composition was expressed by body mass index (BMI) and percent body fat. Changes in cardiorespiratory fitness and body composition between the baseline and the last examination were classified into loss, stable, and gain groups. There were 386 deaths from cancer during an average of 12.5 yr of follow-up. After adjusting for possible confounders and BMI, change hazard ratios (95% confidence intervals) of cancer mortality were 0.74 (0.57-0.96) for stable fitness and 0.74 (0.56-0.98) for fitness gain. Inverse dose-response relationships were observed between changes in maximal METs and cancer mortality (P for linear trend = 0.05). Neither BMI change nor percent body fat change was associated with cancer mortality after adjusting for possible confounders and maximal METs change. In the joint analyses, men who became less fit had a higher risk of cancer mortality (P for linear trend = 0.03) compared with those who became more fit, regardless of BMI change levels. Being unfit or losing cardiorespiratory fitness over time was found to predict cancer mortality in men. Improving or maintaining adequate levels of cardiorespiratory fitness appears to be important for decreasing cancer mortality in men.

Opposing effects of dehydroepiandrosterone sulfate and free testosterone on metabolic phenotype in women with polycystic ovary syndrome

Because of the improved survival rate, both short term and long term adverse effects of breast cancer treatment have become increasingly important. Body weight and body composition before, during, and after chemotherapy may influence side effects during treatment and survival. The aims of this thesis were to assess among stage I-IIIB breast cancer patients: 1) the association between pre-treatment body composition and dose-limiting toxicities during chemotherapy, 2) potential changes in body weight and body composition during and after chemotherapy compared to changes in age-matched women without cancer in the same time period, and 3) dietary intake during chemotherapy compared to age-matched women without cancer in the same time period. Chapter 2 describes the association between pre-treatment body composition and dose-limiting toxicities during chemotherapy. Data from 172 breast cancer patients who participated in the COBRA-study were analysed. Body composition was measured using a total body Dual Energy X-ray Absorption (DEXA) scan. Information regarding dose-limiting toxicities was abstracted from medical records. A higher BMI (kg/m2) and a higher fat mass (kg and percentage) were associated with an increased risk of dose-limiting toxicity, while lean body mass (kg) was not associated with risk of toxicities. Chapter 3 presents the findings of a meta-analysis on changes in body weight during chemotherapy in breast cancer patients. The meta-analysis showed an overall gain in body weight of 2.7 kg (95% CI: 2.0-3.3) during chemotherapy, with a high degree of heterogeneity (I2= 94.2%). Weight gain in breast cancer patients was more pronounced in papers published before 2000 and studies including cyclophosphamide, methotrexate and 5-fluorouracil as chemotherapy regime. Chapter 4 describes changes in body weight and body composition during and after chemotherapy. Data from 145 patients and 121 women of an age-matched comparison group, participating in the COBRA-study were analysed. Body composition was measured using DEXA-scan at three time points during the study period. For the patient group, these tie points were: before start of chemotherapy, shortly after chemotherapy, and 6 months after chemotherapy. For the comparison group these measurements were conducted over a similar time frame: baseline, 6 months after baseline, and 12 months after baseline. In addition, we identified determinants of changes in body weight and body composition. Shortly after chemotherapy, patients had a significantly higher body weight, BMI, and lean body mass than women in the comparison group, while fat mass was similar. Six months after chemotherapy no differences in body weight or body composition were observed between the patient and comparison group. A younger age, better appetite during chemotherapy, and an ER-receptor negative tumour were associated with greater changes in body weight over time. A younger age and better appetite during chemotherapy were associated with greater changes in fat mass over time, while the only determinant associated with greater changes in lean body mass over time was a better appetite during chemotherapy. Chapter 5 describes the dietary intake and food groups before and during chemotherapy of breast cancer patients compared with women without cancer. In addition we assessed the association between symptoms and energy intake. Data from 117 breast cancer patients and 88 women without breast cancer who participated in the COBRA-study were used. Habitual dietary intake before chemotherapy was assessed using a food frequency questionnaire. Two 24-hr dietary recalls were used to assess actual dietary intake during chemotherapy for patients and within 6 months for the comparison group. Shortly after the 24-hr dietary recall, participants filled out questionnaires about symptoms. Before chemotherapy, dietary intake was similar for both groups. During chemotherapy, breast cancer patients reported significantly lower total energy, total fat, total protein, and alcohol intake than women without cancer, which could be explained by a lower intake of specific food groups. Overall results from this thesis suggest that pre-treatment fat mass is associated with dose-limiting toxicities during chemotherapy. Weight gain during chemotherapy appeared to be more modest than we expected based on literature and changes in body composition during chemotherapy consist mainly of an increase in lean body mass, which is only temporary and returned to baseline within 6 months after chemotherapy. A higher appetite during chemotherapy was associated with changes in body weight and body composition. A younger age at diagnosis was associated with greater changes in body weight and fat mass, but not with changes in lean body mass. In addition, an ER-receptor negative tumour was associated with greater changes in body weight, but not with changes in fat mass or lean body mass. During chemotherapy women with breast cancer have a lower intake of energy, fat, protein and alcohol compared to age-matched women without cancer, which was expressed in a lower intake of specific food groups. The results of this thesis do not suggest that dietary intake is associated with weight gain during chemotherapy.

To investigate how body fat influences glucose metabolism and hormone profiles in women with polycystic ovary syndrome (PCOS), compared to women without PCOS. We conducted a cross-sectional study of 166 women with PCOS and 139 age-matched control women at Peking University Third Hospital (Beijing, China) from March 2016 to December 2021. All participants underwent bioimpedance rate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, body composition parameters were assessed, based on the methods used in a previous study. Homeostasis model assessment-insulin resistance (HOMA-IR) and other indices calculated from fasting glucose and insulin were used to measure insulin resistance. The hormonal profiles [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), prolactin (PRL), total testosterone (T), and androstenedione (A2)] were assessed by using biochemical methods. Two subgroup analyses were conducted according to waist-to-hip ratio (WHR; < 0.85, non-central obesity and ≥ 0.85, central obesity) and body fat percentage (BFP; < 35% for lean and ≥35% for obesity). The indices above were analyzed using a two-sided t-test or Wilcoxon rank sum test. Linear regression was used to investigate the effects of body composition on metabolism and sex hormones in the PCOS and control groups. Compared to women without PCOS, women with PCOS and central obesity (P=0.021), PCOS and noncentral obesity (P<0.001), PCOS and high BFP (P<0.001), and PCOS and low BFP (P<0.001) had more severe glucose metabolism evaluated with HOMA-IR. Women with PCOS experienced greater insulin sensitivity impairment than did the normal population for every equal increase in BFP. LH, LH/FSH, total testosterone, and androstenedione were significantly higher in patients with PCOS than in healthy controls, regardless of WHR and BFP stratification. However, negative correlations existed between body fat indices (i.e., BFP and body mass index) and hormone indices (i.e., LH and androstenedione) in the PCOS group, but were absent in the control group. Obese and non-obese women with PCOS have more severe insulin resistance and sex-hormone disorders than women without PCOS. The effect of body fat on sex-hormone disorders is only exist in women with PCOS. These findings suggested that PCOS clinical guidelines should be more specific to body fat. https://clinicaltrials.gov/, Registration No. NCT04264832.

ObjectiveTo determine factors associated with differential changes in body fat, insulin resistance and aerobic capacity following a 12-week exercise intervention in overweight and obese women with and without polycystic ovary syndrome (PCOS).Methods16 overweight and obese women (9 PCOS; 7 without PCOS) completed a supervised progressive 12-week exercise program. Primary outcomes included changes in indicators of insulin sensitivity (including glucose infusion rate relative to fat-free mass [GIR/FFM]), body composition, and aerobic capacity (VO2 peak; 12 participants only). Comparisons were made between women with and without PCOS, and between participants who lost ≥5% (classified as exercise responders) and <5% (non-responders) in body fat (assessed by dual-energy X-ray absorptiometry).ResultsTraining decreased body fat percentage by (mean; 95% CI) -2.3%; -5.3, 0.7% in women with PCOS and by -6.4%; -10.9, -1.9% in women without PCOS (P = 0.08). Ten women (7 PCOS; 3 without PCOS) did not reduce body fat by ≥5%. All participants improved VO2 peak (mean change 27%; 16–39%) but four (2 PCOS; 2 without PCOS) demonstrated decreases in GIR/FFM (mean change for whole cohort: 37%; 3–71%). Android-gynoid fat ratio (0.58; 0.51, 0.66 vs 0.46; 0.40, 0.51; P<0.01) was significantly higher and GIR/FFM (6.69; 3.49, 9.90 vs 11.44; 9.15, 13.72 mg/kg/min; P = 0.01) was significantly lower in non-responders compared with responders at baseline, but non-responders had significant post-training decreases in android-gynoid ratio (-0.02; -0.04, -0.01; P = 0.03), and increases in VO2 peak (7.24; 2.28, 12.21 mL/kg/min; P = 0.01) and GIR/FFM (1.44; 0.27, 2.61 mg/kg/min; P = 0.02). In women with PCOS, pre-training VO2 peak was significantly negatively correlated with change in total body fat (r = -0.75; P = 0.02), and pre-training fasting glucose negatively correlated with changes in VO2 peak (r = -0.76; P = 0.04), but positively correlated with changes in GIR (r = 0.67; P = 0.046).ConclusionA high proportion of overweight and obese women with PCOS had small reductions in body fat following a 12-week exercise intervention, but nevertheless significantly reduced relative central adiposity and improved aerobic capacity and insulin sensitivity.

Previous data suggested a link between maternal polycystic ovary syndrome (PCOS) and offspring attention deficit hyperactivity disorder (ADHD), which could be mediated by higher prenatal androgen exposure. The study was part of the prospective Odense Child Cohort and included 1776 pregnant women, 165 (9%) with PCOS and 1607 (91%) controls. ADHD symptoms at 3years of age were defined using the parent-reported questionnaire Child Behavior Checklist/1.5-5 (scores >90th centile of Danish national standard). Maternal blood samples were collected in the third trimester measuring total testosterone by mass spectrometry, sex hormone-binding globulin, and calculated free testosterone. Offspring anogenital distance was measured at 3months of age. Regression models were performed with presence of ADHD symptoms as the dependent variable and adjusted for maternal age, body mass index, parity, smoking status, educational level, and parental psychiatric diagnoses. ADHD symptoms were present in 105/937 (11%) boys and 72/839 (9%) girls. In boys, maternal PCOS was positively associated with ADHD symptoms (unadjusted odds ratio [OR] 1.91, 95% CI 1.07-3.43, p=0.03, adjusted OR 2.20, 95% CI 1.20-4.02, p=0.01), whereas maternal PCOS was not associated with ADHD symptoms in girls. Maternal total testosterone, free testosterone, and offspring anogenital distance were not associated with higher risk of ADHD symptoms in the offspring. Higher risk of ADHD in boys born of mothers with PCOS were not associated with maternal third-trimester testosterone levels or offspring anogenital distance.

Objective: Women with polycystic ovary syndrome (PCOS) are characterized by insulin resistance and higher prevalence of obesity. Serum ferritin is increased in obesity and is associated with insulin resistance. The aim of the present study was to evaluate the relationships between serum ferritin concentration with insulin resistance and body composition estimated by dual-energy X-ray absorptiometry (DXA) in PCOS women in comparison to the control group.Patients and Methods: One hundred four women were enrolled to the study−65 women with PCOS and 39 women matched for age and BMI as a control group. Serum ferritin concentration and oral glucose tolerance test (OGTT) were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. DXA was performed to estimate fat, fat-free mass, and visceral adipose tissue (VAT).Results: Women with PCOS have higher serum concentration of ferritin (p = 0.002), insulin at baseline (p = 0.03), at 60 min of OGTT (p = 0.01), at 120 min of OGTT (p = 0.004), HOMA-IR (p = 0.03), and VAT (p = 0.0001) in comparison to the control group. We observed a relationship of serum ferritin with insulin concentration at baseline (r = 0.25, p = 0.04) and at 120 min of OGTT (r = 0.31, p = 0.01) and with HOMA-IR (r = 0.30, p = 0.01) in the PCOS group. We noticed an association between serum ferritin concentration and VAT (r = 0.42, p = 0.001), trunk fat mass (r = 0.25, p = 0.04), and android fat mass (r = 0.25, p = 0.04) in the PCOS group. Multiple regression analysis revealed that ferritin (p = 0.02, β = 0.17), insulin at baseline (p = 0.001, β = 0.30), glucose at the 120 min of OGTT (p = 0.007, β = 0.26), and triglycerides (p = 0.001, β = 0.33) were independent predictors of VAT amount in PCOS women.Conclusions: Elevated serum ferritin concentration is connected with insulin resistance as well as with DXA-estimated VAT, android, and trunk fat mass in PCOS women, and could be a marker of metabolic dysfunction.

Do women with PCOS have a unique predisposition to obesity?

Associations Between Sedentary Time, Physical Activity, and Dual-Energy X-ray Absorptiometry Measures of Total Body, Android, and Gynoid Fat Mass in Children