International evidence-based guideline on assessment and management of PCOS-A Nordic perspective.

Polycystic ovary syndrome (PCOS) affects about 12% of women of reproductive age. In 2018, the first evidence-based guideline on assessment and management of PCOS was published, and an updated extended guideline was released in August 2023. These guidelines followed best practice and are endorsed by 39 organizations worldwide, making them the most robust source of evidence to guide clinical practice. In the 2023 guideline, diagnostic criteria have been further refined as polycystic ovary morphology can now be assessed with gynecological ultrasound or elevated anti-Müllerian hormone levels. A healthy lifestyle should be at the focus of care for all women with PCOS; however, with no specific diet or physical exercise recommended. The latest evidence on medical treatments and fertility management are reviewed, including special considerations regarding long-term follow-up of metabolic and psychiatric comorbidities and pregnancy in women with PCOS. Here we summarize the recommendations from a Nordic perspective.

Endometriosis and menopause-management strategies based on clinical scenarios.

Endometriosis is largely considered a premenopausal disease with symptoms often improving during menopausal transition. However, 2%-4% of postmenopausal women are affected by endometriosis symptoms. At the same time, many peri- and postmenopausal women experience menopausal symptoms and inquire about treatment. Because of the estrogen-dependent nature of endometriosis, treatment with menopausal hormone therapy requires careful assessment of the patient but should nevertheless be considered. Recurrence of endometriosis symptoms and risk for malignant transformation are potential risks to weigh when prescribing menopausal hormonal therapy. Choice of treatment should be guided by the presence and severity of current endometriosis symptoms, nature of menopausal symptoms, risk assessment of potential contraindications for treatment in patient history, and preferences of the woman after an informative discussion. Recurrence of endometriosis symptoms in a postmenopausal patient should always prompt rigorous evaluation, both in the presence and absence of hormonal treatment. Many recommendations on the topic are based on expert opinion and new studies are urgently needed to obtain evidence for optimal patient care.

Cognitive profile in adult women with turner syndrome: IQ split and associations with ADHD and ASD.

INTRODUCTION: The behavioural phenotype in Turner syndrome (TS) is associated with an uneven cognitive profile and social and executive difficulties. Still, studies in adult populations of TS are scarce, and the interactions between different behavioural domains are unclear. The aim of this study was to examine the cognitive profile in relation to measures of ADHD and ASD in a Swedish sample of 30 adult women with TS. METHODS: Standardized psychological tests and questionnaires were used for behavioural assessments in a sample of adult women with a diagnosis of TS (n = 30). Both frequentist and Bayesian statistics were applied. RESULTS: The cognitive profile was characterized by a verbal > non-verbal intelligence quotient (IQ) split, and 77% of the sample displayed a split exceeding cut-off for clinical significance. Symptoms on screening measures reaching thresholds for ADHD were reported in two of the 30 participants (7%) and thresholds for autism spectrum disorders (ASD) in one participant (3%). Bayesian statistics gave substantial evidence for no association between the IQ split and symptoms of ADHD/ASD. CONCLUSIONS: These results show that the TS phenotype in adulthood is associated with a clinically significant uneven cognitive profile, and particular impairments in integrative executive functions.

Body Weight Satisfaction, Comments, Nutrition and Injury Risk in 489 Adolescent Elite Athletes.

Exposure to critical body weight comments in youth athletes could lead to decreased self-esteem, affect body image, and increase the risk of eating disorders and cause depressive symptoms. The aim was to explore differences between sex, body mass index, sports type, with regards to body weight satisfaction, exposure to critical body weight comments from their coach and nutrition status in adolescent elite athletes. A questionnaire about body weight, critical body weight comments and nutrition was distributed to 489 adolescent elite athletes and injury prevalence was monitored across 20 weeks. The results showed that almost one in four athletes (n=116, 24%) was not satisfied with their weight and 12% (n=59) had received critical body weight comments from their coach. Of the athletes who were unsatisfied with their body weight (n=116), 47% wanted to lose weight (n=55). A significant (p<0.05) higher proportion of ice hockey players and swimmers used nutritional supplements, were unsatisfied with their body weight, and were more exposed to critical body weight comments compared to athletes from other sports. Adolescent elite athletes as young as 15-16 years old are exposed to critical body weight comments from their coach and experience challenges with body weight satisfaction that is partly dependent on the sport-specific context.

Sexual Function in Women With Differences of Sex Development or Premature Loss of Gonadal Function.

BACKGROUND: Previous studies have suggested that sexual function may be compromised in women born with differences of sex development (DSD) or early loss of gonadal function. AIM: To describe sexual function and sexual wellbeing in women with complete androgen insensitivity syndrome (CAIS), complete gonadal dysgenesis (GD) and premature ovarian insufficiency (POI) in relation to gynecological measures and in comparison with unaffected women. METHODS: A cross sectional study including 20 women with CAIS, 8 women with 46,XY GD, 8 women with 46,XX GD, 21 women with POI, and 62 population-derived controls. Study participants underwent gynecological examination for anatomical measurements and evaluation of tactile sensitivity. They responded to the validated Sexual Activity Log (SAL), Profile of Female Sexual Function (PFSF), and the Personal Distress Scale (PDS). RESULTS: The women with CAIS, XY GD, XX GD and POI showed overall satisfying sexual function in comparison to unaffected age-matched population female controls with a median of 1 to 2 satisfying sexual episodes per week among both the patients and the controls depending on available partner. Women with CAIS had shorter vagina and smaller clitoris and women with XY GD had a significantly shallower vagina in comparison to controls. Clitoral width was also significantly smaller among women with XX GD compared to controls. However, results showed overall good genital touch sensitivity with no significant differences between groups. CLINICAL IMPLICATIONS: Women with DSD or POI can be informed on overall satisfactory sexual function and normal genital touch sensitivity. STRENGTHS & LIMITATIONS: The strength is the use of age-matched population-based controls to these rare conditions of DSD and POI. Limitations are the nonresponder rate of recruited controls, as well as the small groups of women with DSD. CONCLUSION: Women with differences of sex development or early loss of gonadal function show overall good sexual well-being, however clinicians have to make efforts to optimize caretaking and treatment to ensure good sexual quality of life for all patients. Engberg H, Strandqvist A, Berg E, et al., Sexual Function in Women With Differences of Sex Development or Premature Loss of Gonadal Function. J Sex Med 2022;19:249-256.

Interaction between insulin and androgen signalling in decidualization, cell migration and trophoblast invasion in vitro.

Finely tuned decidualization of endometrial stromal fibroblasts into decidual cells is crucial for successful implantation and a healthy pregnancy. Both insulin and androgens are known to modulate decidualization, however, their complex effect on this process has not been fully elucidated. As hyperinsulinemia and hyperandrogenism are associated in clinical conditions, we aimed to investigate the interaction between insulin and androgens on decidualization. Primary human endometrial stromal cells were decidualized in vitro in the presence of insulin and/or androgens (dihydrotestosterone (DHT), testosterone). Gene or protein expressions of decidualization markers were measured, and cells size characteristics were determined. Migration of decidualizing endometrial stromal cells and invasion of HTR-8/SVneo trophoblast spheroids were assessed. We found that insulin and androgens in combination enhanced the upregulation of several decidualization markers including prolactin, tissue factor, tissue inhibitor of matrix metalloproteinase 3 and connexin-43, and also interacted in modulating cell size characteristics resulting in enlarged decidualizing cells. However, insulin and DHT together restricted the migration of decidualizing cells and invasion of trophoblast spheroids. Our findings suggest that insulin and androgens interact to potentiate the process of decidualization. On the other hand, inhibited cell migration and trophoblast invasion might negatively impact the function of decidualizing endometrial stromal cells.

Dihydrotestosterone potentiates insulin to up-regulate prokineticin-1 in decidualizing human endometrial stromal cells.

Prokineticin 1 (PROK1) is a key regulator of embryo implantation and placentation, and its dysregulation is associated with pregnancy complications, such as pre-eclampsia and foetal growth restriction. We have previously shown that insulin strongly enhances the expression of PROK1 in human decidualizing stromal cells. Here, we demonstrate that dihydrotestosterone (DHT), but not testosterone, potentiates insulin to up-regulate PROK1 in these cells. However, the androgens alone do not influence the expression of PROK1. Our findings suggest that insulin and androgens both are involved in the regulation of PROK1 that could have implications for normal and pathological pregnancies.

A Phase II Prospective, Randomized, Double-Blind, Placebo-Controlled and Multicenter Clinical Trial to Assess the Safety of 0.005% Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women with Early Stage Breast Cancer in Treatment with Aromatase Inhibitor in the Adjuvant Setting.

LESSONS LEARNED: The levels of circulating follicle-stimulating hormone, luteinizing hormone, estriol, estradiol, and estrone remained unchanged after a 12-week treatment with 0.005% estriol vaginal gel in postmenopausal women receiving nonsteroidal aromatase inhibitors for hormone receptor-positive early breast cancer. These results support the safety of 0.005% estriol vaginal gel for the treatment of bothering symptoms of vulvovaginal atrophy in breast cancer survivors. The results provide clinicians with confidence in the use of this product in women who do not experience symptom relief with nonhormonal remedies. BACKGROUND: Symptoms of vulvovaginal atrophy associated with treatment with nonsteroidal aromatase inhibitors (NSAIs) negatively impact patients' quality of life and may affect adherence to NSAIs. Vaginal estrogens effectively improve these symptoms, although their safe use in breast cancer survivors remains unclear. METHODS: Postmenopausal women with hormone receptor-positive early breast cancer receiving NSAI and moderate-to-severe vaginal dryness were randomized to 0.005% estriol vaginal gel or placebo for 12 weeks. Circulating estrogens, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), were analyzed at baseline and at weeks 1, 3, 8, and 12. The primary safety outcome was the variation in serum FSH from baseline to week 12. RESULTS: Sixty-one women (mean age, 59 years) enrolled in the study. Small oscillations were observed in FSH and LH, although they were always maintained within the postmenopausal range. No significant differences were found in the variation of FSH and LH between baseline and week 12 from the physiological variation observed before treatment. Women receiving 0.005% estriol vaginal gel had slightly increased estriol levels at weeks 1 and 3, with a subsequent reduction until normalizing at week 12; estradiol and estrone remained the below limit-of-quantitation in almost all samples. CONCLUSION: Ultralow-dose 0.005% estriol vaginal gel did not significantly influence estrogens, FSH, and LH levels in women with breast cancer receiving NSAI. A transient negligible absorption of estriol and a nonsignificant variation of FSH after 12 weeks were observed. These findings provide confidence for the safe use of 0.005% estriol vaginal gel in women with breast cancer with an indication for treatment with vaginal estrogens.

Women with polycystic ovary syndrome present with altered endometrial expression of stanniocalcin-1†.

Stanniocalcin-1 (STC-1) is a pro-survival factor that protects tissues against stressors, such as hypoxia and inflammation. STC-1 is co-expressed with the endometrial receptivity markers, and recently endometrial STC-1 was reported to be dysregulated in endometriosis, a condition linked with endometrial progesterone resistance and inflammation. These features are also common in the endometrium in women with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. Given that women with PCOS present with subfertility, pregnancy complications, and increased risk for endometrial cancer, we investigated endometrial STC-1 expression in affected women. Endometrial biopsy samples were obtained from women with PCOS and controls, including samples from overweight/obese women with PCOS before and after a 3-month lifestyle intervention. A total of 98 PCOS and 85 control samples were used in immunohistochemistry, reverse-transcription polymerase chain reaction, or in vitro cell culture. STC-1 expression was analyzed at different cycle phases and in endometrial stromal cells (eSCs) after steroid hormone exposure. The eSCs were also challenged with 8-bromo-cAMP and hypoxia for STC-1 expression. The findings indicate that STC-1 expression is not steroid hormone mediated although secretory-phase STC-1 expression was blunted in PCOS. Lower expression seems to be related to attenuated STC-1 response to stressors in PCOS eSCs, shown as downregulation of protein kinase A activity. The 3-month lifestyle intervention did not restore STC-1 expression in PCOS endometrium. More studies are warranted to further elucidate the mechanisms behind the altered endometrial STC-1 expression and rescue mechanism in the PCOS endometrium.

Endometrial expression of anti-Müllerian hormone and its type II receptor in women with polycystic ovary syndrome.

RESEARCH QUESTION: Is endometrial expression of anti-Müllerian hormone (AMH) and its receptor II (AMH-R) altered in women with polycystic ovary syndrome (PCOS) and affected by lifestyle intervention? DESIGN: Endometrial immunostaining of AMH and AMH-R was evaluated in obese women with PCOS (OB-PCOS, n = 18) before and after 3 months of lifestyle intervention, as well as in BMI-matched controls (OB-C, n = 10), normal-weight women with PCOS (n = 11) and healthy normal-weight controls (n = 11). RESULTS: Before lifestyle modification, serum concentrations of AMH were higher in women with PCOS compared with BMI-matched controls, but there were no differences in endometrial immunostaining of AMH or AMH-R between the groups. Following lifestyle modification, a subgroup of OB-PCOS women started to ovulate. Still, there were no differences in endometrial immunostaining of AMH between ovulatory and anovulatory women with PCOS and controls, and no variation within the menstrual cycle. However, immunostaining of stromal AMH-R increased from cycle days 6-8 to 21-23 in all three groups. Furthermore, endometrial immunostaining of AMH-R correlated positively with oestrogen receptor alpha on cycle days 21-23 in the groups of women with PCOS, as well as in the controls (r = 0.66, P = 0.007 and r = 0.85, P < 0.001, respectively). CONCLUSIONS: Although PCOS is associated with increased serum concentrations of AMH, protein expression of AMH and its receptor in the endometrium was no different to controls, and moreover not affected by lifestyle modification. These results imply that circulating AMH is not affecting expression of AMH and its receptor in the endometrium.

Association between prolactin receptor expression and proliferation in the endometrium of obese women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with increased risk of endometrial cancer. There is growing evidence that prolactin and its receptor (PRLR) are involved in the development of cancer. We assessed endometrial expression of PRLR mRNA, and immunostaining of PRLR and the proliferation marker Ki67 on different cycle days in obese (OB-PCOS) and normal-weight women with PCOS and body mass index-matched controls. The OB-PCOS group underwent a 3 months lifestyle intervention. Prior to intervention, obese women with PCOS and controls had lower endometrial levels of PRLR mRNA in proliferative endometrium than the normal-weight groups (p < .05). After intervention, six OB-PCOS women had confirmed ovulation, while 12 remained anovulatory. Both these subgroups displayed higher immunostaining of PRLR in endometrial stroma, and in the anovulatory subgroup also increased Ki67, on cycle days 21-23 compared with controls (p < .05). In obese controls, the PRLR mRNA expression was decreased in secretory endometrium compared with proliferative endometrium (p = .004). A corresponding change within the cycle was not found in OB-PCOS women. Immunostaining of PRLR in the secretory phase correlated positively with Ki67 (p < .05) in the endometrium. These observations suggest that short-term lifestyle intervention can restore ovulation but not normalize PRLR expression in the endometrium of obese women with PCOS. Trial registration: ISRCTN, ISRCTN18400086, https://doi.org/10.1186/ISRCTN18400086.

Effects of moderately increased testosterone concentration on physical performance in young women: a double blind, randomised, placebo controlled study.

OBJECTIVE: To investigate the effects of a moderate increase in serum testosterone on physical performance in young, physically active, healthy women. METHODS: A double blind, randomised, placebo controlled trial was conducted between May 2017 and June 2018 (ClinicalTrials.gov ID: NCT03210558). 48 healthy, physically active women aged 18-35 years were randomised to 10 weeks of treatment with 10 mg of testosterone cream daily or placebo (1:1). All participants completed the study. The primary outcome measure was aerobic performance measured by running time to exhaustion (TTE). Secondary outcomes were anaerobic performance (Wingate test) and muscle strength (squat jump (SJ), counter movement jump (CMJ) and knee extension peak torque). Hormone levels were analysed and body composition assessed by dual energy X-ray absorptiometry. RESULTS: Serum levels of testosterone increased from 0.9 (0.4) nmol/L to 4.3 (2.8) nmol/L in the testosterone supplemented group. TTE increased significantly by 21.17 s (8.5%) in the testosterone group compared with the placebo group (mean difference 15.5 s; P=0.045). Wingate average power, which increased by 15.2 W in the testosterone group compared with 3.2 W in the placebo group, was not significantly different between the groups (P=0.084). There were no significant changes in CMJ, SJ and knee extension. Mean change from baseline in total lean mass was 923 g for the testosterone group and 135 g for the placebo group (P=0.040). Mean change in lean mass in the lower limbs was 398 g and 91 g, respectively (P=0.041). CONCLUSION: The study supports a causal effect of testosterone in the increase in aerobic running time as well as lean mass in young, physically active women.

Mice exposed to maternal androgen excess and diet-induced obesity have altered phosphorylation of catechol-O-methyltransferase in the placenta and fetal liver.

BACKGROUND/OBJECTIVES: Maternal obesity together with androgen excess in mice negatively affects placental function and maternal and fetal liver function as demonstrated by increased triglyceride content with dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage. To identify changes in molecular pathways that might promote diseases in adulthood, we performed a global proteomic analysis using a liquid-chromatography/mass-spectrometry system to investigate total and phosphorylated proteins in the placenta and fetal liver in a mouse model that combines maternal obesity with maternal androgen excess. METHODS: After ten weeks on a control diet (CD) or high fat/high sugar-diet, dams were mated with males fed the CD. Between gestational day (GD) 16.5 and GD 18.5, mice were injected with vehicle or dihydrotestosterone (DHT) and sacrificed at GD 18.5 prior to dissection of the placentas and fetal livers. Four pools of female placentas and fetal livers were subjected to a global proteomic analysis. Total and phosphorylated proteins were filtered by ANOVA q < 0.05, and this was followed by two-way ANOVA to determine the effect of maternal obesity and/or androgen exposure. RESULTS: In placenta, phosphorylated ATP-citrate synthase was decreased due to maternal obesity, and phosphorylated catechol-O-methyltransferase (COMT) was differentially expressed due to the interaction between maternal diet and DHT exposure. In fetal liver, five total proteins and 48 proteins phosphorylated in one or more sites, were differentially expressed due to maternal obesity or androgen excess. In fetal liver, phosphorylated COMT expression was higher in fetus exposed to maternal obesity. CONCLUSION: These results suggest a common regulatory mechanism of catecholamine metabolism in the placenta and the fetal liver as demonstrated by higher phosphorylated COMT expression in the placenta and fetal liver from animals exposed to diet-induced maternal obesity and lower expression of phosphorylated COMT in animals exposed to maternal androgen excess.

Improved menstrual function in obese women with polycystic ovary syndrome after behavioural modification intervention-A randomized controlled trial.

OBJECTIVE: Lifestyle intervention is the recommended first-line treatment for overweight women with polycystic ovary syndrome (PCOS). However, the efficacy of lifestyle change in improving reproductive function is still unclear. DESIGN: A randomized controlled trial (RCT) with allocation to a behavioural modification programme (intervention) or minimal intervention (control) for 4 months with a follow-up at 12 months. PATIENTS: Sixty-eight women, aged 18-40 years, body mass index (BMI) ≥ 27 kg/m2 , fulfilling all Rotterdam PCOS criteria were randomized to treatment. MEASUREMENTS: The primary outcome was improved menstrual regularity. Secondary outcomes were ovulation and pregnancy rates. RESULTS: At 4 months, the weight loss was significant in the intervention group (-2.1%, P = 0.002) and nonsignificant in the control group (-1.0%). A higher proportion of patients in the intervention group improved menstrual regularity compared to the control group, mean difference 35% (95% CI: 16-60), P = 0.003. There was no difference in ovulation rate between groups. Logistic regression analysis showed that intervention was the only predictor of improved menstrual function, OR 3.9 (95% CI: 1.3-11.9). At 12 months, a total of 54% of the women improved menstrual regularity compared to baseline (P = 0.000) and 43% (P = 0.000) had confirmed ovulation. 38% of the women wishing to become pregnant succeeded within 1 year of study completion. CONCLUSIONS: This is the first RCT in overweight women with PCOS showing efficacy in improving reproductive function following behavioural modification intervention in comparison with minimal intervention. Although extensive weight loss is difficult to achieve in these women, behavioural modification intervention can help improve reproductive function.

Changes in premenstrual symptoms in women starting or discontinuing use of oral contraceptives.

It is not clear whether oral contraceptive (OC) treatment affects premenstrual symptoms in women. The aim of the present study was to evaluate changes in premenstrual symptoms (PMS) in women starting to use or discontinuing the use of OCs. Twenty-four healthy women with no previous diagnosis of premenstrual dysphoric disorder were included in this study with a prospective crossover design. Nineteen women completed daily ratings of somatic and mood symptoms during two hormonally different cycles, during a normal menstrual cycle and while using OCs. The menstrual cycle phases were hormonally verified and the low-dose, monophasic OCs were used in a 21/7 regimen. The onset of OC use significantly decreased premenstrual somatic symptoms, but it did not affect mood symptoms. In the women who discontinued OC use, no significant changes in neither somatic nor mood symptoms appeared in the premenstrual phase.

Prokineticin 1 is up-regulated by insulin in decidualizing human endometrial stromal cells.

Prokineticin 1 (PROK1), a hypoxia-regulated angiogenic factor, has emerged as a crucial regulator of embryo implantation and placentation. Dysregulation of PROK1 has been linked to recurrent pregnancy loss, pre-eclampsia, foetal growth restriction and preterm birth. These pregnancy complications are common in women with obesity and polycystic ovary syndrome, i.e. conditions associated with insulin resistance and compensatory hyperinsulinaemia. We investigated the effect of insulin on PROK1 expression during in vitro decidualization. Endometrial stromal cells were isolated from six healthy, regularly menstruating women and decidualized in vitro. Insulin induced a significant dose-dependent up-regulation of PROK1 on both mRNA and protein level in decidualizing endometrial stromal cells. This up-regulation was mediated by hypoxia-inducible factor 1-alpha (HIF1α) via the phosphatidylinositol 3-kinase (PI3K) pathway. Furthermore, we demonstrated that PROK1 did not affect the viability, but significantly inhibited the migration of endometrial stromal cells and the migratory and invasive capacity of trophoblast cell lines. This in vitro study provides new insights into the regulation of PROK1 by insulin in human decidualizing endometrial stromal cells, the action of PROK1 on migration of endometrial stromal cells, as well as migration and invasion of trophoblasts. We speculate that hyperinsulinaemia may be involved in the mechanisms by which PROK1 is linked to placenta-related pregnancy complications.

The prevalence of Type 2 diabetes is not increased in normal-weight women with PCOS.

STUDY QUESTION: Is oral glucose tolerance test (OGTT) needed in all women with polycystic ovary syndrome (PCOS)? SUMMARY QNSWER: OGTT is not routinely needed in women with PCOS and BMI < 25 kg/m2. WHAT IS KNOWN ALREADY: PCOS is associated with insulin resistance and increased prevalence of prediabetes and Type 2 diabetes (T2D) which is closely linked to obesity and possibly age, ethnicity and PCOS phenotype. Several guidelines recommend OGTT upon diagnosis of PCOS and during follow-up. STUDY DESIGN, SIZE, DURATION: A Nordic cross-sectional study including 876 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 876 Nordic women with PCOS, aged 14-57 years, were examined for T2D and prediabetes (impaired glucose tolerance [IGT] or impaired fasting glucose (IFG) by OGTT. MAIN RESULT AND THE ROLE OF CHANCE: Of all study subjects 3% (23/876) had T2D, 23% (204/876) prediabetes and 74% (649/876) had normal glucose tolerance (NGT). Increased BMI and waist circumference were significantly (P < 0.001) associated with prevalence of prediabetes and T2D. No normal-weight woman (BMI < 25 kg/m2) was diagnosed with T2D. The prevalence of BMI ≥ 25 kg/m2 was 66% (578/ 876). 91% of women (21/23) with T2D had BMI ≥ 30 kg/m2. Testosterone levels and PCOS phenotype did not predict 2-h glucose levels during OGTT after adjustment for BMI and age. LIMITATIONS, REASONS FOR CAUTION: The present study included cross-sectional data and prospective studies are needed to confirm our results. These results may not apply to populations of other ethnic origin. WIDER IMPLICATIONS OF THE FINDINGS: Routine OGTT may not be indicated in normal-weight women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Serum androgen profile and physical performance in women Olympic athletes.

BACKGROUND: The role of endogenous androgens for body composition and physical performance in women athletes is still not elucidated. AIM: To examine the serum androgen profile in relation to body composition and physical performance in women Olympic athletes and to compare endocrine variables and body composition to controls. STUDY DESIGN: Cross-sectional study, conducted between 2011 and 2015 at the Women's Health Research Unit, Karolinska University Hospital, Stockholm. METHODS: Swedish women Olympic athletes (n=106) and age-matched and body mass index-matched sedentary controls (n=117) were included in the study. Blood sampling was performed in a rested, fasting state for the measurement of serum androgens and their metabolites by liquid chromatography-tandem mass spectrometry. Body composition was determined by dual-energy X-ray absorptiometry (controls n=100, athletes n=65). The athletes performed standardised performance tests (n=59) (squat jump (SJ) and countermovement jump (CMJ). RESULTS: The athletes demonstrated significantly higher levels of the precursor androgens dehydroepiandrosterone (DHEA) and 5-androstene-3ß, 17ß-diol (5-DIOL) and the metabolite etiocholanolone glucuronide (Etio-G), significantly lower levels of estrone (p<0.05, respectively), higher bone mineral density (p<0.001) and more lean mass (p<0.001) compared with controls. Serum levels of DHEA, 5-DIOL and Etio-G correlated positively to lean mass variables and physical performance in the athletes. DHEA and lean mass legs explained 66% of the variance in SJ, whereas lean mass explained 52% of the variance in CMJ. CONCLUSIONS: The present data suggest that endogenous androgens are associated with a more anabolic body composition and enhanced performance in women athletes. These results are of importance for the current discussion regarding hyperandrogenism in women athletes.

Should we individualize lipid profiling in women with polycystic ovary syndrome?

STUDY QUESTION: Is it necessary to monitor lipid profiles in all young women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Lipid profiling is required when women with PCOS develop type 2 diabetes (T2D) or hypertension, but rarely changes clinical care before the age of 35 years. WHAT IS KNOWN ALREADY: PCOS consensus statements and guidelines recommend that women with PCOS should be screened for dyslipidaemia every second year or annually. STUDY DESIGN, SIZE, DURATION: Women from Denmark, Norway, Finland and Sweden, who had participated in research projects or clinical trials or in whom lipid profiles had been determined routinely as part of clinical care since 2000 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: One thousand three hundred and twenty-seven women with PCOS (Rotterdam criteria) were included. Based on individual cardiovascular risk score and lipid levels, treatment level was guided by the European Society of Cardiology and the European Atherosclerosis Society Task Force for the management of dyslipidaemias. Change in clinical care was defined as need to (i) immediately start statin treatment or (ii) consider statin treatment if life-style intervention fails. MAIN RESULTS AND THE ROLE OF CHANCE: All in all, 74 (5.6%) women with PCOS should immediately start statin treatment, and statin treatment should be considered in 33 women (2.5%). Among women with T2D, 27/28 (96.4%) should initiate statin treatment and the corresponding number for women with hypertension was 42/57 (73.7%). In PCOS women who had not yet developed T2D or hypertension, lipid profiling only changed clinical care in 28 (2.3%). This number was further reduced to 12 (1.2%) in women below the age of 35 years, and to zero in normal-weight women below the age of 35 years. LIMITATIONS, REASONS FOR CAUTION: Findings can only be generalized to countries with low cardiovascular mortality rates. WIDER IMPLICATIONS OF THE FINDINGS: Lipid profiling is required when women with PCOS develop T2D or hypertension. However, lipid profiling rarely changes the clinical care of low risk PCOS patients before the age of 35, especially in the normal-weight women. STUDY FUNDING/COMPETING INTERESTS: The Academy of Finland, Sigrid Juselius Foundation and the Nordic Federation of Obstetrics and Gynecology. There are no conflicts of interest to be declared.

Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study.

Sex hormones and the serotonergic system interact in the regulation of mood, learning, memory and sexual behaviour. However, the mechanisms have not been fully explored. The serotonin transporter protein (5-HTT) regulates synaptic concentrations of serotonin and is a primary target for selective serotonin reuptake inhibitors. The aim of this study was to explore how estrogen treatment alone or in combination with testosterone affects 5-HTT binding potentials measured by positron emission tomography (PET) in specific brain regions of postmenopausal women. Ten healthy surgically postmenopausal women (years since oophorectomy 7.5 ± 4.0, mean ± SD) underwent PET examinations at baseline, after three months of estrogen treatment (transdermal estradiol 100 µg/24 hours) and after another three months of combined estrogen and testosterone (testosterone undecanoate 40 mg daily) treatment using the radioligand [(11)C] MADAM developed for examination of the serotonin transporter. The 5-HTT binding potentials decreased significantly in several cortical regions, as well as in limbic and striatal regions after both estrogen treatment alone and combined estrogen/testosterone treatment in comparison to baseline. The observed decrease in 5-HTT could either be due to direct effects on serotonin transporter expression or be the result of indirect adaptation to estrogen and /or testosterone effects on synaptic serotonin levels. Although the mechanism still needs further exploration, the study supports the view that gonadal hormones play a role in serotonin regulated mood disorders.