Menstrual pattern in polycystic ovary syndrome and hypothalamic-pituitary-ovarian axis immaturity in adolescents: a systematic review and meta-analysis.

OBJECTIVE: To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. RESULTS: Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. CONCLUSIONS: The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.

Reorganization of brain structural networks in aging: A longitudinal study.

Normal aging is characterized by structural and functional changes in the brain contributing to cognitive decline. Structural connectivity (SC) describes the anatomical backbone linking distinct functional subunits of the brain and disruption of this communication is thought to be one of the potential contributors for the age-related deterioration observed in cognition. Several studies already explored brain network's reorganization during aging, but most focused on average connectivity of the whole-brain or in specific networks, such as the resting-state networks. Here, we aimed to characterize longitudinal changes of white matter (WM) structural brain networks, through the identification of sub-networks with significantly altered connectivity along time. Then, we tested associations between longitudinal changes in network connectivity and cognition. We also assessed longitudinal changes in topological properties of the networks. For this, older adults were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24). WM structural networks were derived from diffusion magnetic resonance imaging, and cognitive status from neurocognitive testing. Our results show age-related changes in brain SC, characterized by both decreases and increases in connectivity weight. Interestingly, decreases occur in intra-hemispheric connections formed mainly by association fibers, while increases occur mostly in inter-hemispheric connections and involve association, commissural, and projection fibers, supporting the last-in-first-out hypothesis. Regarding topology, two hubs were lost, alongside with a decrease in connector-hub inter-modular connectivity, reflecting reduced integration. Simultaneously, there was an increase in the number of provincial hubs, suggesting increased segregation. Overall, these results confirm that aging triggers a reorganization of the brain structural network.

Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?

Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up-regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light.

Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels.

Exposure to an excess of androgen or estrogen can induce changes in reproductive function in adult animals that resemble polycystic ovary syndrome in humans. However, considerable differences exist among several types of animal models. Little is known about the molecular features of steroidogenesis and folliculogenesis in the ovaries of rats exposed to different sex steroids as neonates. Here, we evaluated the impact of androgen and estrogen exposure on the ovaries of adult female rats during their neonatal period in the gene expression of Lhr and Cyp17a1, two key players of steroidogenesis. We also assessed hormone levels, folliculogenesis and the theca-interstitial cell population. The study was performed on the second postnatal day in thirty female Wistar rats that were sorted into the following three intervention groups: testosterone, estradiol and vehicle (control group). The animals were euthanized 90 days after birth. The main outcomes were hormone serum levels, ovary histomorphometry and gene expression of Lhr and Cyp17a1 as analyzed via quantitative real-time PCR. We found that exposure to excess testosterone in early life increased the LH and testosterone serum levels, the LH/FSH ratio, ovarian theca-interstitial area and gene expression of Lhr and Cyp17a1 in adult rats. Estrogen induced an increase in the ovarian theca-interstitial area, the secondary follicle population and gene expression of Lhr and Cyp17a1. All animals exposed to the sex steroids presented with closed vaginas. Our data suggest that testosterone resulted in more pronounced reproductive changes than did estrogen exposure. Our results might provide some insight into the role of different hormones on reproductive development and on the heterogeneity of clinical manifestations of conditions such as polycystic ovary syndrome.

Analysis of fatigue development during elite male handball matches.

This study aimed at describing the physiological demands and fatigue development during elite male handball matches. Our hypothesis was that players perform multiple high-intensity activities during periods of the game and develop temporary and end-match neuromuscular fatigue. Time-motion analyses and heart rate (HR) recordings were performed in 40 players during 12 competitive matches. Blood samples were collected, and sprint, jump, and intermittent exercise performance (Yo-Yo Intermittent Endurance level 2 test [YYIE2]) was assessed for 18 players at baseline conditions and after 2 competitive matches, and additional blood sampling and testing were performed for 12 of these players during a friendly match. The time spent with high-intensity running (4.4 ± 2.0 to 3.1 ± 1.7%), the frequency of demanding actions (61 ± 5 to 54 ± 6), and the time with HR above 80% HRmax (62 ± 21 to 41 ± 17%) were lowered from the first to the second half. Average blood lactate during the match was 3.6 ± 2.1 (1.3-8.6) mM. Plasma free fatty acids (FFA), glycerol, glucose, and uric acid increased (p ≤ 0.05) during the first half and plasma FFA and glycerol increased further (p ≤ 0.05) during the second half. After an intense period in the second half, sprint performance was decreased by 3.9 ± 4.9%. After the match, YYIE2 (33.4 ± 8.7%), vertical jump (7.4 ± 6.5%), and 20-m sprint performance (1.6 ± 2.6%) was lower (p ≤ 0.05) than at baseline. This study showed that the intensity is high in certain periods during elite male handball games and that physical performance is impaired both temporarily during and toward the end of games confirming our hypothesis. These findings enables physical trainers and coaches to plan and design proper game-specific training exercises aiming at delaying both temporary and end-game fatigue and strengthen the physiological rationale for the need for substitutions in various stages of match-play.

Physiological demands of elite team handball with special reference to playing position.

This study aimed to analyze the physiological demands of match play for different playing positions in elite male team handball. Time motion (N = 30) and heart rate (HR; N = 70) data were recorded throughout 10 official matches. The mean distance covered by backcourt players (4.96 ± 0.64 km) was greater (p ≤ 0.02) than for wings and pivots (4.23 ± 0.52 and 3.91 ± 0.51 km, respectively). Backcourt players spent less time standing still and walking (∼76%) than wings and pivots (∼80%) (p ≤ 0.03), and wings spent more time sprinting than the other playing positions. Backcourt players (122.9 ± 17.0) and pivots (126.8 ± 33.0) performed more high-demanding actions per game than wings (54.6 ± 15.6) (p = 0.01). The time spent by pivots in high-intensity activities decreased from the first to the second half (4.1 ± 2.4 to 2.7 ± 0.9%; p ≤ 0.01), while backcourt players showed a decrease in high-demanding playing actions (p ≤ 0.05). Backcourt players and pivots had higher mean (84 ± 9 and 83 ± 9% vs. 79 ± 10%; p ≤ 0.03) and peak effective HR, and percentage of total time at intensities >80% maximal HR (HRmax) than wings. The fraction of total time spent at intensities >80% HRmax decreased for all outfield playing positions in the second half (from 39-76 to 30-46%). Competitive team handball involves position-specific differences in the physiological demands. Furthermore, exercise intensity decreases from the first to the second half for all outfield playing positions suggesting that these players experience neuromuscular fatigue. Training of elite handball players should comprise high-intensity position-specific exercises aiming at improving the ability to maintain a high exercise intensity throughout the game.

Comparison of promestriene with vaginal fractional CO2 laser and radiofrequency treatments of genitourinary syndrome of menopause.

OBJECTIVE: To compare the effects of fractional CO2 laser and microablative fractional radiofrequency treatment with promestriene topical estrogen on sexual function and genitourinary syndrome of menopause symptoms. METHODS: This was a prospective randomized open-label clinical trial conducted with 62 postmenopausal women assigned to three intervention groups: a) topical promestriene for 90 days (n = 17); b) fractional CO2 laser treatment (n = 24); and c) microablative fractional radiofrequency treatment (n = 21). Each of the latter two groups underwent three treatment sessions at 4-week intervals. At baseline and at the end of the study, all participants had a gynecological examination that included vaginal pH measurement, and the completion of the Vaginal Symptom Score, the Vaginal Health Index, and the Female Sexual Function Index. For the energy treatment groups, adverse effects were evaluated after each session. Group homogeneity was assessed at baseline, and results were evaluated over time (from baseline to the end of treatment) and between groups over time. RESULTS: All baseline parameters were similar among studied groups. At the end of the study, all 3 treatments had produced similar effects: a reduction of vaginal pH, and an improvement of vulvovaginal symptoms (Vaginal Symptom Score and Vaginal Health Index scores) as well as sexual function (higher total Female Sexual Function Index scores, and in the desire, arousal, lubrication and pain domain scores), with no differences observed between groups. Side-effects were slight for both energy treatment groups, mainly represented by vaginal discharge. CONCLUSION: The present study suggests that the two energy treatments were efficient along with promestriene at improving postmenopausal genitourinary and sexuality symptoms. Clinical trial identification numberNCT04717245.

Are former athletes more prone to asthma?

OBJECTIVE: We have designed the present study to compare prevalent lifetime cases of diagnosed asthma or exercise-induced asthma, as well as current related respiratory symptoms, across two different levels of former athletes and non-athletes. METHODS: Demographic, behavioral, and asthma history information, as well as current related respiratory symptoms, were obtained through a questionnaire from 627 subjects (290 former elite and 201 non-elite athletes that competed between 1969 and 2005, and 136 control subjects that had never been athletes). RESULTS: Non-athletes presented a higher percentage of subjects reporting the existence of symptoms associated with exercise or vigorous activities. Former athletes who reported having practiced mostly in indoor facilities presented significant lower risk for asthma than outdoor athletes (Odds Ratio = 0.48, 95% CI = 0.25-0.94). Multiple regression analysis (where "B" refers to unstandardized coefficients) showed that former elite (B = -0.85, p < .001) and non-elite athletes (B = -0.70, p < .001) were less prone to be affected by asthma-related symptoms than non-athletes. Athletes with careers that lasted more than 20 years were more likely to possess asthma-related symptoms than the ones with shorter careers (3-7 years, B = -0.47, p < .001; 8-14 years, B = -0.42, p < .01; 15-20, B = -0.32, p < .05). CONCLUSIONS: Non-athletes seem to have a higher prevalence of respiratory symptoms. Among former athletes, career characteristics seem to play a crucial role, with special emphasis to its duration, where the most lengthy seem to be more associated with respiratory symptoms.

Physical and physiological demands of elite team handball.

This study aimed to analyze elite team handball physical and physiological demands during match play. Time-motion (N = 30) and heart rate (HR; N = 60) analyses were performed throughout 10 official matches. The defined locomotor categories were standing still, walking, jogging, fast running, sprinting, backwards movement, sideways medium-intensity movement, and sideways high-intensity movement, and playing actions studied were jumps, shots, stops when preceded by high-intensity activities, changes of direction and one-on-one situations. During matches, the mean distances covered were 4,370 ± 702.0 m. Around 80% of the total time was spent standing still (43.0 ± 9.27%) and walking (35.0 ± 6.94%) and only 0.4 ± 0.31% with sprinting. The most frequent high-intensity actions were stops, changes of direction, and one-on-one situations. Effective mean HR was 157 ± 18.0 b·min(-1) (82 ± 9.3% of HRmax), and total HR was 139 ± 31.9 b·min(-1) (72 ± 16.7% of HRmax). The HR, time spent in high-intensity activities, frequency of stops, changes of direction, one-on-one situations, and most intense periods of the game were higher during the first half than during the second half (p ≤ 0.05). The opposite was observed for the number of time outs and the time between each change of activity (p = 0.00). Handball is an intermittent exercise that primarily uses aerobic metabolism, interspersed by high-intensity actions that greatly tax anaerobic metabolism. Additionally, exercise intensity decreases from the first to the second half of the match, suggesting that neuromuscular fatigue may occur during the game. The training of elite handball players should comprise exercises targeting the ability to perform specific high-intensity actions throughout the game and to rapidly recover during the less intense periods.

Injuries in youth soccer during the preseason.

OBJECTIVE: To evaluate injuries occurring during the preseason in youth soccer players. DESIGN: Prospective cohort study over 1 preseason. SETTING: 2009-2010 preseason. PARTICIPANTS: Subjects were 912 youths aged 12 to 19 years. ASSESSMENT OF RISK FACTORS: The club's medical staff prospectively recorded all injuries. A reportable injury was defined as by the consensus statement on soccer injuries. Estimated injury rates per 1000 hours of exposure during the preseason period were calculated. MAIN OUTCOME MEASURES: Injury rates (injuries per 1000 hours of soccer exposure) during preseason practices by age group, as well as prevalence, severity, and type of injuries. RESULTS: Total incidence was 2.5 injuries per 1000 hours of exposure. Incidence of match and training injuries were 6.7 and 1.8 injuries per 1000 hours (P = 0.02), respectively. Injuries were sustained by 7.2% of players during the preseason, and 79% of the injuries involved the lower limbs, of which 23% were located to the thigh. Muscle strains and contusions were the most common injuries and external trauma the main cause. CONCLUSIONS: No age-related trend in the incidence of preseason injuries was found. During the preseason training period, athletic trainers should expect a majority of muscle strains, especially in the thigh region.

Interplay Between the Salience and the Default Mode Network in a Social-Cognitive Task Toward a Close Other.

Social cognition relies on two main subsystems to construct the understanding of others, which are sustained by different social brain networks. One of these social networks is the default mode network (DMN) associated with the socio-cognitive subsystem (i.e., mentalizing), and the other is the salience network (SN) associated with the socio-affective route (i.e., empathy). The DMN and the SN are well-known resting state networks that seem to constitute a baseline for the performance of social tasks. We aimed to investigate both networks' functional connectivity (FC) pattern in the transition from resting state to social task performance. A sample of 38 participants involved in a monogamous romantic relationship completed a questionnaire of dyadic empathy and underwent an fMRI protocol that included a resting state acquisition followed by a task in which subjects watched emotional videos of their romantic partner and elaborated on their partner's (Other condition) or on their own experience (Self condition). Independent component and ROI-to-ROI correlation analysis were used to assess alterations in task-independent (Rest condition) and task-dependent (Self and Other conditions) FC. We found that the spatial FC maps of the DMN and SN evidenced the traditional regions associated with these networks in the three conditions. Anterior and posterior DMN regions exhibited increased FC during the social task performance compared to resting state. The Other condition revealed a more limited SN's connectivity in comparison to the Self and Rest conditions. The results revealed an interplay between the main nodes of the DMN and the core regions of the SN, particularly evident in the Self and Other conditions.

Signatures of white-matter microstructure degradation during aging and its association with cognitive status.

Previous studies have shown an association between cognitive decline and white matter integrity in aging. This led to the formulation of a "disconnection hypothesis" in the aging-brain, which states that the disruption in cortical network communication may explain the cognitive decline during aging. Although some longitudinal studies have already investigated the changes occurring in white matter microstructure, most focused on specific white matter tracts. Our study aims to characterize the longitudinal whole-brain signatures of white matter microstructural change during aging. Furthermore, we assessed the relationship between distinct longitudinal alterations in white matter integrity and cognition. White matter microstructural properties were estimated from diffusion magnetic resonance imaging, and cognitive status characterized from extensive neurocognitive testing. The same individuals were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24) between first and last assessment. Our results show that age is associated with a decline in cognitive performance and a degradation in white matter integrity. Additionally, significant associations were found between diffusion measures and different cognitive dimensions (memory, executive function and general cognition). Overall, these results suggest that age-related cognitive decline is related to white matter alterations, and thus give support to the "disconnected hypothesis" of the aging brain.

Acupuncture ameliorated vasomotor symptoms during menopausal transition: single-blind, placebo-controlled, randomized trial to test treatment efficacy.

OBJECTIVES: This study aimed to evaluate the effects of acupuncture on women with vasomotor symptoms during the menopausal transition with the aid of the Kupperman-Blatt Menopausal Index. METHOD: Crossover, single-blind, sham-controlled trial with 100 women randomly divided into two groups of 50 participants each: G1 and G2. During the first 24 weeks of treatment, the G1 women received acupuncture and the G2 women were given sham acupuncture. The crossover was then applied: the G1 participants were given sham acupuncture, and the G2 participants received acupuncture for 24 more weeks. RESULTS: The mean score of hot flashes of the group who first experienced acupuncture (G1) was statistically higher than that of the group that started with sham acupuncture (G2, P = 0.020). Also, both groups had similar mean scores in the middle of the study (both were receiving acupuncture). During the last 6 months of the study, after crossover, the values of G2 (acupuncture) were lower than those of G1 (sham acupuncture). CONCLUSIONS: Acupuncture treatment may mitigate hot flashes and other climacteric symptoms during the menopausal transition.

Video Summary:http://links.lww.com/MENO/A641.

Estrogen effects on pilocarpine-induced temporal lobe epilepsy in rats.

OBJECTIVE: To evaluate the effects of conjugated equine estrogens (CEE) on the pilocarpine-induced epilepsy in rats. STUDY DESIGN: 40 female rats were divided into: GPC (positive control) presented "status epilepticus" (SE) induced by pilocarpine; GOC (ovariectomized control) only castrated; GNC (negative control) received only saline solution; GPE received pilocarpine, presented SE, castrated and received 50microg/kg CEE treatment; GPV received pilocarpine, castrated and received propylene glycol (vehicle). The animals were monitored by a video system. At the end of observation, the brains removed for later histologic analysis using Neo-Timm and Nissl methods. RESULTS: The GPE presented a reduction in number of seizures compared to GPV. The Neo-Timm analysis showed that GPV had greater sprouting of mossy fibers, with a denser band in the area of the dentate gyrus hilum compared to GPE. On Nissl staining, GPE showed evident neuronal loss in the CA3 area. GPV presented loss in CA1 and dentate gyrus. CONCLUSION: Estrogen may have a protecting effect on the central nervous system.

Using resting-state DMN effective connectivity to characterize the neurofunctional architecture of empathy.

Neuroimaging studies in social neuroscience have largely relied on functional connectivity (FC) methods to characterize the functional integration between different brain regions. However, these methods have limited utility in social-cognitive studies that aim to understand the directed information flow among brain areas that underlies complex psychological processes. In this study we combined functional and effective connectivity approaches to characterize the functional integration within the Default Mode Network (DMN) and its role in self-perceived empathy. Forty-two participants underwent a resting state fMRI scan and completed a questionnaire of dyadic empathy. Independent Component Analysis (ICA) showed that higher empathy scores were associated with an increased contribution of the medial prefrontal cortex (mPFC) to the DMN spatial mode. Dynamic causal modelling (DCM) combined with Canonical Variance Analysis (CVA) revealed that this association was mediated indirectly by the posterior cingulate cortex (PCC) via the right inferior parietal lobule (IPL). More specifically, in participants with higher scores in empathy, the PCC had a greater effect on bilateral IPL and the right IPL had a greater influence on mPFC. These results highlight the importance of using analytic approaches that address directed and hierarchical connectivity within networks, when studying complex psychological phenomena, such as empathy.

Asymmetrical subcortical plasticity entails cognitive progression in older individuals.

Structural brain asymmetries have been associated with cognition. However, it is not known to what extent neuropsychological parameters and structural laterality covary with aging. Seventy-five subjects drawn from a larger normal aging cohort were evaluated in terms of MRI and neuropsychological parameters at two moments (M1 and M2), 18 months apart. In this time frame, asymmetry as measured by structural laterality index (ΔLI) was stable regarding both direction and magnitude in all areas. However, a significantly higher dispersion for this variation was observed in subcortical over cortical areas. Subjects with extreme increase in rightward lateralization of the caudate revealed increased M1 to M2 Stroop interference scores, but also a worsening of general cognition (MMSE). In contrast, subjects showing extreme increase in leftward lateralization of the thalamus presented higher increase in Stroop interference scores. In conclusion, while a decline in cognitive function was observed in the entire sample, regional brain asymmetries were relatively stable. Neuropsychological trajectories were associated with laterality changes in subcortical regions.

Effect of sildenafil on clitoral blood flow and sexual response in postmenopausal women with orgasmic dysfunction.

OBJECTIVE: To analyze the effects of sildenafil citrate on clitoral blood flow and sexual response in postmenopausal women with orgasmic dysfunction. METHOD: In this randomized, double-blind, placebo-controlled trial 22 women received a 50-mg dose of sildenafil (n=11) or placebo (n=11) daily for 15 days. The Golombok Rust Inventory of Sexual Satisfaction (GRISS) was used for subjective evaluation of the sexual-response cycle. Clitoral blood flow was measured by color and pulse Doppler at baseline, after 1 hour of taking the first dose, and after 15 days of treatment. RESULTS: Blood flow was significantly more improved in the sildenafil than in the placebo group (P<0.05), and a positive correlation between Doppler values and GRISS scores was noted in the sildenafil group after only 15 days of treatment. CONCLUSION: Sildenafil may improve clitoral blood flow and increase the GRISS scores in postmenopausal women with orgasmic dysfunction.

Empathy by default: Correlates in the brain at rest.

BACKGROUND: Empathy, defined as the ability to access and respond to the inner world of another person, is a multidimensional construct involving cognitive, emotional and self-regulatory mechanisms. Neuroimaging studies report that empathy recruits brain regions which are part of the social cognition network. Among the different resting state networks, the Default Mode Network (DMN) may be of particular interest for the study of empathy since it has been implicated in social cognition tasks. METHOD: The current study compared the cognitive and emotional empathy scores, as measured by the Interpersonal Reactivity Index, with the patterns of activation within the DMN, through the neuroimaging methodology of resting-state functional magnetic resonance. RESULTS: Results suggest a significant positive correlation between cognitive empathy and activation of the bilateral superior medial frontal cortex nodes of the DMN. Contrastingly, a negative correlation was found between emotional empathy and the same brain region. CONCLUSIONS: Overall, this data highlights a critical role of the medial cortical regions of the DMN, specifically its anterior node, for both cognitive and emotional domains of the empathic process.

Functional Hemispheric (A)symmetries in the Aged Brain-Relevance for Working Memory.

Functional hemispheric asymmetries have been described in different cognitive processes, such as decision-making and motivation. Variations in the pattern of left/right activity have been associated with normal brain functioning, and with neuropsychiatric diseases. Such asymmetries in brain activity evolve throughout life and are thought to decrease with aging, but clear associations with cognitive function have never been established. Herein, we assessed functional laterality during a working memory task (N-Back) in a healthy aging cohort (over 50 years old) and associated these asymmetries with performance in the test. Activity of lobule VI of the cerebellar hemisphere and angular gyrus was found to be lateralized to the right hemisphere, while the precentral gyrus presented left > right activation during this task. Interestingly, 1-Back accuracy was positively correlated with left > right superior parietal lobule activation, which was mostly due to the influence of the left hemisphere. In conclusion, although regions were mostly symmetrically activated during the N-Back task, performance in working memory in aged individuals seems to benefit from lateralized involvement of the superior parietal lobule.