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Background Although polycystic ovary syndrome (PCOS) is a very common endocrinopathy, there are several issues related to this disorder which perplex clinicians in their everyday practice. Objective To determine the current state of knowledge among European endocrinologists concerning the full spectrum of PCOS. Methods An online survey comprising 41 items covering various aspects of PCOS diagnosis and management was distributed to members of the European Society of Endocrinology. Results A total of 505 European endocrinologists (64% females), with a mean age of 47 ± 11.6 years, participated in the survey. The Rotterdam criteria were the primary diagnostic tool for 85% of respondents. Most referrals (87.1%) occurred between ages 20 and 40 years. Twenty-five percent of physicians have access to mass spectrometry for the evaluation of androgen levels. While an extended metabolic profile was commonly employed as part of the workup, there was uncertainty regarding chronic anovulation diagnosis. Diabetes, including gestational or type 2, was recognized as a significant risk factor with universal screening irrespective of BMI status. Lifestyle modification and metformin were considered as standard interventions by all participants alongside oral contraceptives, though there was significant discrepancy in treatment duration. Conclusions The Rotterdam diagnostic criteria are widely adopted for PCOS diagnosis among European endocrinologists. The current updated survey shows an emphasis on steroid profiling as an important part of diagnostic workup and a strong position held for recognition of PCOS as a metabolic condition with potentially serious implications. Current therapy thus shifted to the demand for prioritizing lifestyle interventions and metabolic therapies, either as monotherapy or in combination with standard hormone compounds. [ABSTRACT FROM AUTHOR]

Background Multiples of resting metabolic rate (RMR) are often used to classify physical activity intensity, a concept known as the metabolic equivalent of task (MET). However, the METs metrics may misclassify physical activity intensity in older adults because of age-related changes in RMR and maximal aerobic capacity (⁠ V ˙ O 2 max). This study aimed to (i) compare classifications of activity intensity by estimated (METsestimated) and measured (METsmeasured) METs and (ii) compare physical activity classified by absolute (METsmeasured) versus relative intensity (% V ˙ O 2 Reserve) in older adults. Methods Ninety-eight adults aged 75–90 years participated in the study. RMR and V ˙ O 2 during sitting, standing, daily activities, and 6-minute walking test were measured. V ˙ O 2 Reserve was defined as the difference between V ˙ O 2 max and RMR. Moderate and vigorous intensity was classified as 3 and 6 METs and 40% and 60% of V ˙ O 2 Reserve, respectively. Paired t tests and a confusion matrix were used to investigate aims 1 and 2, respectively. Results METsmeasured was 24% lower than the standard 1 MET of 3.5 mL O2·min−1·kg−1. METsestimated underestimated the intensity during daily and walking activities when compared to METsmeasured. Nevertheless, when comparing METsmeasured to percentages of V ˙ O 2 Reserve, a mismatch was shown for moderate intensity in 47%–67% of the participants during daily activities and 21% of the participants during self-selected gait speed. Conclusions Applying METsestimated for older adults leads to potential underestimation of physical activity intensity, suggesting that current classification metrics should be revised for older adults. V ˙ O 2 Reserve is a candidate metric for establishing precise physical activity intensity cut points for older adults. Clinical Trials Registration Number: NCT04821713 [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does anogenital distance (AGD) – distance from the anus to the genitals – correlate from infancy (3 months) to the age of 9 years in boys and girls? SUMMARY ANSWER In boys, AGD correlated from infancy to 9 years of age, whereas in girls, correlations were weaker, especially between infancy and later childhood. WHAT IS KNOWN ALREADY AGD is considered a marker for prenatal androgen action. In males, reduced AGD is associated with testicular cancer, infertility, and lower sperm count. In females, AGD is associated with endometriosis and polycystic ovary syndrome. STUDY DESIGN, SIZE, DURATION In the Odense Child Cohort, a prospective population-based birth cohort, pregnant women were enrolled in early pregnancy. AGD and BMI were measured repeatedly in children at ages 3 and 18 months, as well as at 3, 5, 7, and 9 years. PARTICIPANTS/MATERIALS, SETTING, METHODS AGD was measured from the anus to the scrotum (AGDas) and to the penis (AGDap) in 1022 boys, and to the posterior fourchette and the clitoris in 887 girls repeatedly between the age of 3 months to 9 years. In total, 7706 assessments were made. AGD was adjusted for body weight, and SD scores (the difference between individual AGD and the mean of AGD in the population divided by SD of AGD) were calculated for each child. Pearson correlation coefficient (r) of each measurement was performed to investigate whether individual AGD was stable during childhood. Short predictive values at 3 months (20th percentile) to 9 years were investigated using the AUC produced by the receiver operating characteristic curve. MAIN RESULTS AND THE ROLE OF CHANCE In boys, AGD/body size-index SD score correlated significantly between infancy and 9 years, strongest for AGDas (r  = 0.540 P  > 0.001). In girls, weaker significant correlation coefficients were found between AGD at infancy and 9 years; higher correlation coefficients were found between AGD from 3 to 9 years (P  > 0.001). Short AGDas in infancy predicted short AGDas in boys aged 9 years (AUC: 0.767, sensitivity 0.71, specificity 0.71). The predictive values of short infant AGDap, penile width (in boys), and AGD (in girls) concerning short outcomes at 9 years were low. LIMITATIONS, REASONS FOR CAUTION The AGD measurements are less precisely measurable in girls compared to boys, especially in infancy, resulting in less reproducible measurements. Additionally, because AGD is shorter in girls, the same absolute measurement error is relatively more significant, potentially contributing to greater variability and lower reproducibility in girls. This may contribute to the weaker correlations in girls compared to boys. WIDER IMPLICATIONS OF THE FINDINGS In boys, AGDas, relative to body size, correlated from infancy to 9 years, suggesting that AGD in infancy can be considered a non-invasive marker of later reproductive health. Further follow-up studies are needed to evaluate long-term individual tracking of AGD as well as assessment of childhood AGD as early marker of adult reproductive health. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, the Municipality of Odense, Denmark, the University of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, the Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), Sygeforsikring Danmark (journalnr. 2021-0173), the Collaborative Foundation between Odense University Hospital and Rigshospitalet, and Helsefonden. There is no conflict of interest of any author that could be perceived as prejudicing the impartiality of the research reported. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Simple Summary: Pituitary adenomas often regrow after surgery, posing a treatment challenge. By studying the DNA methylation patterns of these adenomas, we aimed to identify different subtypes that may predict regrowth potential. Samples from 33 patients with nonfunctioning pituitary adenomas were analyzed, revealing distinct DNA methylation clusters. While trends suggesting certain clusters might be associated with higher regrowth potential emerged, overall significant differences in regrowth rates between these clusters were not found. DNA methylation profiling could help identify adenomas prone to regrowth, potentially improving treatment strategies in the future. Further larger studies are needed to confirm the findings from this explorative pilot study. Background: The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. Methods: A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007–2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. Results: The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. Conclusion: The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study. [ABSTRACT FROM AUTHOR]

Objective: To study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer and mortality. Methods: Pertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990-1999, 2000-2009, and 2010-2021) based on the year of diagnosis or treatment initiation. Results: Adenoma size and insulin-like growth factor I (IGF-I) levels at diagnosis did not differ significantly between study periods. The risk of being diagnosed with diabetes, heart disease, sleep apnea, joint disease, and osteoporosis increased from the 1990s to the later decades, while the mortality risk declined to nearly half. The risk of cancer did not significantly change. Treatment changed toward the use of more medical therapy, and fewer patients underwent repeat surgeries or pituitary irradiation. A statistically significant increase in the proportion of patients achieving IGF-I normalization within 3-5 years was observed over time (69%, 83%, and 88%). The proportion of patients with three or more deficient pituitary hormones decreased significantly over time. Conclusion: Modern medical treatment regimens of acromegaly as well as increased awareness and improved diagnostics for its comorbidities have led to better disease control, fewer patients with severe hypopituitarism, and declining mortality in the Danish cohort of acromegaly patients. The risk of cancer did not increase over the study period. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The association between gestational diabetes mellitus (GDM) and incident kidney disease, the mediating effects of diabetes and hypertension, and the impact of severity of metabolic dysfunction during pregnancy on the risk of incident kidney disease were investigated in this study. RESEARCH DESIGN AND METHODS: This Danish, nationwide, register-based cohort study included all women giving birth between 1997 and 2018. Outcomes included chronic kidney disease (CKD) and acute kidney disease, based on diagnosis codes. Cox regression analyses explored the association between GDM and kidney disease. A proxy for severity of metabolic dysfunction during pregnancy was based on GDM diagnosis and insulin treatment during GDM in pregnancy and was included in the models as an interaction term. The mediating effects of subsequent diabetes and hypertension prior to kidney disease were quantified using mediation analyses. RESULTS: Data from 697,622 women were used. Median follow-up was 11.9 years. GDM was associated with higher risk of CKD (adjusted hazard ratio [aHR] 1.92; 95% CI 1.67–2.21), whereas acute kidney disease was unrelated to GDM. The proportions of indirect effects of diabetes and hypertension on the association between GDM and CKD were 75.7% (95% CI 61.8–89.6) and 30.3% (95% CI 25.2–35.4), respectively, as assessed by mediation analyses. The CKD risk was significantly increased in women with insulin-treated GDM and no subsequent diabetes compared with women without GDM (aHR 2.35; 95% CI 1.39–3.97). CONCLUSIONS: The risk of CKD was significantly elevated after GDM irrespective of subsequent development of diabetes and hypertension. Furthermore, women with severe metabolic dysfunction during pregnancy had the highest CKD risk. [ABSTRACT FROM AUTHOR]

Introduction: Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre‐pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. Material and methods: Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z‐scores. Linear regression models were used to estimate the effect of metformin on offspring z‐scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S‐testosterone, s‐androstenedione, and s‐sex‐hormone binding globulin from four timepoints in pregnancy were analyzed. Results: Compared with the PCOS‐placebo group, newborns in the PCOS‐metformin group had larger head circumference (head circumference z‐score: mean difference = 0.25, 95% CI = 0.11– 0.40). This effect of metformin on head circumference z‐score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS‐phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS‐placebo group were shorter than in the reference population (birth length z‐score: mean = −0.04, 95% CI = –0.05 to −0.03), but head circumference and birthweight were similar. Conclusions: Larger head circumference was observed at birth in metformin‐exposed offspring of mothers with PCOS. PCOS‐offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight‐to‐height ratio at birth. [ABSTRACT FROM AUTHOR]

Background: Testosterone replacement therapy in aging men increases lean body mass and decreases whole‐body fat. The safety of testosterone replacement therapy concerning cardiovascular disease is unresolved and assessment of whole‐body oxidative stress may contribute to future decision making. Objectives: To determine whole‐body oxidative stress during testosterone replacement therapy and placebo in aging men and evaluate if a change in oxidative stress was mediated by changed body composition. Materials and methods: This was a double‐blinded, randomized, placebo‐controlled study for 24 weeks in 38 men aged 60–78 years with bioavailable testosterone <7.3 nmol/L and waist circumference ≥94 cm who were randomized to testosterone replacement therapy (testosterone gel) (N = 20) or placebo (N = 18). At baseline and after 24 weeks, whole‐body oxidative stress was assessed by oxidized derivatives of nucleic acids, 8‐oxoguanosine and 8‐oxo‐2′‐deoxyguanosine in 24‐h urine samples by ultra‐performance liquid chromatography tandem mass spectrometry. Lean body mass and whole‐body fat were measured by dual X‐ray absorptiometry. Subcutaneous and visceral adipose tissue were estimated by magnetic resonance imaging. Testosterone replacement therapy versus placebo was compared by Mann–Whitney tests on ∆‐values (24–0 weeks). Results: Baseline age was 67 (64–72) years (median [interquartile range]), body mass index 29.8 (26.6–33.3) kg/m2, waist 107 (99–117) cm, and bioavailable testosterone 4.7 (3.7–5.9) nmol/L. During testosterone replacement therapy, 8‐oxoguanosine in 24‐h urine samples decreased from 21.6 (19.8; 27.7) nm to 15.0 (12.2; 18.8) nm (p = 0.038 vs. placebo), lean body mass increased (p < 0.01) and whole‐body fat (p = 0.02) and subcutaneous adipose tissue (p < 0.01) decreased. 8‐Oxoguanosine in 24‐h urine samples was inversely associated with Δ‐lean body mass (ρ = –0.38, p = 0.03), which remained significant after adjusting for Δ‐total testosterone. 8‐Oxo‐2′‐deoxyguanosine in 24‐h urine samples was unchanged (p = 0.06) during testosterone replacement therapy and Δ‐8‐oxo‐2′‐deoxyguanosine in 24‐h urine samples was associated with Δ‐whole‐body fat (kg) (ρ = 0.47, p < 0.01). Δ‐Values of oxidative stress biomarkers were not associated with Δ‐fasting insulin or Δ‐homeostatic model assessment of insulin resistance. Discussion: Oxidative stress decreased during testosterone replacement therapy compared to placebo, which could be mediated by changed body composition. Conclusion: Whole‐body oxidative stress decreased during 24 weeks of testosterone replacement therapy in aging men. [ABSTRACT FROM AUTHOR]

The Buss-Perry Aggression-Questionnaire (AQ) is an American trait-aggression assessment tool. It has 29 items under four dimensions of Physical and Verbal Aggression, Anger, and Hostility. The Short Aggression-Questionnaire (SH-AQ) is a 12-item version of the AQ. Danish translations of these questionnaires have not previously been developed, and the aim of this study was to translate and validate Danish versions of the AQ and the SH-AQ. The AQ underwent forward and back translation, review by expert committee, and pilot-testing. A general population sample of 641 participants answered a digital version of the AQ. We used confirmatory factor analysis to evaluate three structural models for the AQ, the SH-AQ, and two alternative versions with modifications to the Physical Aggression-dimension. Gender differences were analyzed using independent t-tests. The SH-AQ had better fit-parameters than the AQ, but the 12-item Alternative-SH-AQ showed the overall best model-fit. The Four-Factor structure was superior to the other models. Men had higher scores than women on all dimensions except for Hostility. While there was support for the validity of the SH-AQ and partial support for the AQ, the Alternative-SH-AQ provided the best model-fit and the highest response spread, and we recommend this version for research on aggression in Denmark. [ABSTRACT FROM AUTHOR]