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Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition that results in cortisol deficiency and excess production of adrenal androgens. While the introduction of newborn screening for CAH has reduced morbidity and mortality, management of CAH remains challenging. Lifelong treatment with glucocorticoids is required to replace the endogenous cortisol deficiency and reduce excess adrenal androgens. Undertreatment or overtreatment with glucocorticoids can lead to multiple disease- and treatment-related comorbidities, including impaired growth and compromised final height, menstrual irregularities and reduced fertility in females, and long-term cardiometabolic complications. In addition to avoiding adrenal crisis and sudden death, treatment goals in adolescent females with CAH are to obtain normal growth and bone maturation and normal timing of puberty. Management of adolescents is particularly challenging due to changes in growth and sex hormone levels that can lead to inadequate suppression of adrenal androgens and increasing independence that can affect treatment adherence. During the transition to adult care, treatment goals focus on preventing symptoms of hyperandrogenism, preserving menstrual regularity and fertility, and providing education and support for issues related to sexuality, atypical genitalia, and/or complications from previous surgical treatment. In addition, patients must be monitored continuously to prevent long-term complications such as decreased bone mineral density, obesity, diabetes, and hypertension. In this review, we discuss the challenges faced by adolescent and adult females with CAH and provide guidance to health-care professionals to help patients to navigate these challenges. [ABSTRACT FROM AUTHOR]

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18–40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care. Baseline subcutaneous adipose tissue gene expression was related to weight change after the lifestyle intervention. A total of 55 obese/overweight women provided subcutaneous adipose samples at study entry. Weight loss was significant after behavioral modification (−2.2%, p = 0.0014), while there was no significant weight loss in the control group (−1.1%, p = 0.12). In microarray analysis of adipose samples, expression of 40 genes differed significantly between subgroups of those with the greatest weight loss or weight gain. 10 genes were involved in metabolic pathways including glutathione metabolism, gluconeogenesis, and pyruvate metabolism. Results were confirmed by real-time polymerase chain reaction (RT-PCR) in all 55 subjects. Expressions of GSTM5, ANLN, and H3C2 correlated with weight change (R = −0.41, p = 0.002; R = −0.31, p = 0.023 and R = −0.32, p = 0.016, respectively). GSTM5, involved in glutathione metabolism, was the strongest predictor of weight loss, and together with baseline waist-hip ratio (WHR) explained 31% of the variation in body weight change. This study shows that baseline subcutaneous adipose tissue genes play a role for body weight outcome in response to lifestyle intervention in overweight/obese women with PCOS. [ABSTRACT FROM AUTHOR]

Background Increased access to and indications for genetic testing will lead to more women undergoing risk-reducing salpingo-oophorectomy (RRSO), with a potential impact on sexual function. Aim Our objective was to prospectively investigate (1) sexual function in women with pathogenic variant (PV) in BRCA1/2 genes, before and 1 year after RRSO, and to compare with a healthy age-matched control group and (2) to study if testosterone levels correlate with sexual functioning after RRSO. Methods A prospective observational follow-up study of 43 BRCA1/2 -PV carriers planned for RRSO and 73 healthy-age matched controls. Data including personal medical history, the Female Sexual Function Index (FSFI) and blood samples for analysis of testosterone by tandem mass spectrometry and free androgen index (FAI) were collected before and 1 year after surgery or at inclusion (controls). Outcomes Sexual function and testosterone levels following RRSO. Results Median age in the RRSO group was 42 years at baseline, 55.8% were premenopausal and 53.5% had a history of breast cancer. The RRSO group had significantly lower median FSFI total score (P  < .001), lower scores of all 6 FSFI domains (P  < .001), as well as a higher proportion of female sexual dysfunction (FSD) (P  < .001) compared to the control group at 1 year after surgery. In the RRSO group, users of menopausal hormone therapy (MHT) had a significantly higher median FSFI total score compared with the nonusers both at baseline (P  = .023) and follow-up (P  = .010). The proportion of FSD was significantly higher in the non-MHT group at both baseline (P  = .041) and follow-up (P  = .009). FAI was significantly lower in the RRSO group when compared to the controls at 1-year follow-up (P  = .041); however, no significant correlations between testosterone levels and FSFI scores were found. Clinical implications The results highlight the need to counsel BRCA1/2 -PV carriers before RRSO and offer a structured follow-up and support addressing sexual function and impact of MHT use. Strengths and Limitations The main strength of this study is its prospective design with age-matched controls. Limitation is a small sample size. Conclusion Our findings show that sexual function deteriorated 1 year after RRSO independent of testosterone levels, and the proportion with impaired sexual function was higher compared to healthy age-matched controls. [ABSTRACT FROM AUTHOR]

This non-randomized controlled trial aimed to compare the effect of the 5:2 diet on insulin levels as a primary outcome and markers of insulin secretion (connecting peptide (C-peptide) and insulin-like growth factor binding protein-1 (IGFBP-1)) and sensitivity (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), as well as body composition as secondary outcomes in overweight/obese individuals with and without type 2 diabetes (T2D). Ninety-seven participants (62% women), 35 with T2D and 62 BMI- and waist-matched controls without T2D, followed the 5:2 diet (two days per week of fasting) for six months with a 12-month follow-up. At six months, there was no loss to follow-up in the T2D group, whereas four controls discontinued this study. Overall, 82% attended the 12-month follow-up. After the intervention, insulin levels decreased in the control group and glucose decreased in the T2D group, while C-peptide, HOMA-IR, waist circumference, BMI, trunk, and total fat% decreased in both groups. Furthermore, low IGFBP-1, indicating hyperinsulinemia, improved in the T2D group. The changes in fasting glucose and waist measurement were significantly more improved in the T2D group than in the controls. Persistent positive effects were observed at the 12-month follow-up. The 5:2 diet for six months was feasible and efficient to reduce markers of insulin secretion and resistance and therefore holds promise as management of overweight/obesity in subjects with and without T2D. [ABSTRACT FROM AUTHOR]

Hyperandrogenism in women, such as polycystic ovary syndrome, ovarian hyperthecosis, congenital adrenal hyperplasia, and androgen-secreting tumors, are all associated with increased prevalence of cardiovascular risk factors that include type 2 diabetes, hypertension, dyslipidemia, and metabolic syndrome. However, it is not clear whether this also implies enhanced risk of cardiovascular disease and mortality. Furthermore, the involvement of obesity and menopausal status for cardiometabolic risk in these women has not been elucidated. Based on the most recent systematic reviews and meta-analyses, this review summarizes the latest scientific evidence. To conclude, hyperandrogenism in premenopausal women is associated with enhanced prevalence of cardiovascular risk factors, as well as increased risk of cardiovascular disease and mortality, independently of body mass index. In contrast, elevated cardiovascular risk factors and increased risk of myocardial infarction and stroke in hyperandrogenic postmenopausal women are dependent on obesity. Furthermore, the overall risk of cardiovascular disease and coronary artery disease in hyperandrogenic postmenopausal women is similar to controls. The reason for a reduced cardiometabolic risk after menopause in hyperandrogenic women compared to nonhyperandrogenic women is not clear. It can be speculated that the difference in endocrine balance and metabolic status between women with and without hyperandrogenism might decrease after menopause because hyperandrogenism usually improves with age, whereas menopausal transition itself is associated with androgen dominance and abdominal obesity. Although we have gained increased knowledge about cardiometabolic risks in women with hyperandrogenism, it must be acknowledged that the quality of data is overall low. More research is needed, especially longer and larger follow-up studies in women with hyperandrogenism of different etiologies and phenotypes. [ABSTRACT FROM AUTHOR]

Background: The menstrual cycle and its impact on training and performance are of growing interest. However, evidence is lacking whether periodized exercise based on the menstrual cycle is beneficial. The primary purpose of this proposed randomized, controlled trial, the IMPACT study, is to evaluate the effect of exercise periodization during different phases of the menstrual cycle, i.e., comparing follicular phase-based and luteal phase-based training with regular training during the menstrual cycle on physical performance in well-trained women. Methods: Healthy, well-trained, eumenorrheic women between 18 and 35 years (n = 120) will be recruited and first assessed for physical performance during a run-in menstrual cycle at different cycle phases and then randomized to three different interventions: follicular phase-based training, luteal phase-based training, or regular training during three menstrual cycles. The training intervention will consist of high-intensity spinning classes followed by strength training. The menstrual cycle phases will be determined by serum hormone analysis throughout the intervention period. Assessment of aerobic performance (primary outcome) and muscle strength, body composition, and blood markers will be performed at baseline and at the end of the intervention. Discussion: With a robust methodology, this study has the potential to provide evidence of the differential effects of exercise periodization during different phases of the menstrual cycle in female athletes. Trial registration: ClinicalTrials.gov NCT05697263. Registered on 25 January 2023 Key message: • The menstrual cycle has the potential to affect sporting performance in female athletes. Female athletes do perceive the impact of the menstrual cycle on physical performance. • This randomized, controlled trial will provide evidence of any differential effects of exercise periodization during different phases of the menstrual cycle in female athletes. • The results of this study might lead to new training recommendations given to exercising women. [ABSTRACT FROM AUTHOR]