A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

Pulmonary Embolism With Pulmonary Infarction in a Patient Using the Annovera® Segesterone Acetate and Ethinylestradiol Combined Vaginal Contraceptive Ring.

Combined hormonal contraceptives (CHC) are a very popular form of contraception among young women. Recently, vaginal contraceptive rings (VCR) have been formulated, offering greater convenience and ease of use. Venous thromboembolism (VTE) has been associated with CHC use and is a significant cause of mortality and morbidity in women. Here, we present the case of a 48-year-old woman who presented with right upper quadrant abdominal pain for four days associated with one day of shortness of breath. She had a history of anemia and abnormal uterine bleeding due to uterine fibroids. She was found to have a large embolus in the right pulmonary artery, associated with a right lower lobe pulmonary infarction. No evidence of lower-extremity deep venous thrombosis was found. She was using a segesterone acetate and ethinylestradiol combination VCR, which was removed. She was started on intravenous heparin anticoagulation with improvement in symptoms. This was later transitioned to an oral apixaban regimen prior to discharge. The exact mechanism of CHC-induced thrombotic risk remains unclear. They affect numerous proteins involved in the coagulation, anticoagulation, and thrombolytic pathways, thereby expressing their net thrombogenic potential. Estrogens have often been implicated as the more thrombogenic hormone, with progestogens being added to mitigate some of the risks. CHC use can cause a sixfold increased risk for VTE. Reducing the dose of estrogen and proper patient selection with attention to their risk profile remain essential for the safe use of these agents. This represents the first case report relating segesterone acetate and ethinylestradiol combination VCR to pulmonary embolism and infarction.

Effect of Menstrual Cycle and Hormonal Contraception on Musculoskeletal Health and Performance: Protocol for a Prospective Cohort Design and Cross-Sectional Comparison.

BACKGROUND: Women of reproductive age experience cyclical variation in the female sex steroid hormones 17ß-estradiol and progesterone during the menstrual cycle that is attenuated by some hormonal contraceptives. Estrogens perform a primary function in sexual development and reproduction but have nonreproductive effects on bone, muscle, and sinew tissues (ie, ligaments and tendons), which may influence injury risk and physical performance. OBJECTIVE: The purpose of the study is to understand the effect of the menstrual cycle and hormonal contraceptive use on bone and calcium metabolism, and musculoskeletal health and performance. METHODS: A total of 5 cohorts of physically active women (aged 18-40 years) will be recruited to participate: eumenorrheic, nonhormonal contraceptive users (n=20); combined oral contraceptive pill (COCP) users (n=20); hormonal implant users (n=20); hormonal intrauterine system users (n=20); and hormonal injection users (n=20). Participants must have been using the COCP and implant for at least 1 year and the intrauterine system and injection for at least 2 years. First-void urine samples and fasted blood samples will be collected for biochemical analysis of calcium and bone metabolism, hormones, and metabolic markers. Knee extensor and flexor strength will be measured using an isometric dynamometer, and lower limb tendon and stiffness, tone, and elasticity will be measured using a Myoton device. Functional movement will be assessed using a single-leg drop to assess the frontal plane projection angle and the qualitative assessment of single leg loading. Bone density and macro- and microstructure will be measured using ultrasound, dual-energy x-ray absorptiometry, and high-resolution peripheral quantitative computed tomography. Skeletal material properties will be estimated from reference point indentation, performed on the flat surface of the medial tibia diaphysis. Body composition will be assessed by dual-energy x-ray absorptiometry. The differences in outcome measures between the hormonal contraceptive groups will be analyzed in a one-way between-group analysis of covariance. Within the eumenorrheic group, the influence of the menstrual cycle on outcome measures will be assessed using a linear mixed effects model. Within the COCP group, differences across 2 time points will be analyzed using the paired-samples 2-tailed t test. RESULTS: The research was funded in January 2020, and data collection started in January 2022, with a projected data collection completion date of August 2024. The number of participants who have consented at the point of manuscript submission is 66. It is expected that all data analysis will be completed and results published by the end of 2024. CONCLUSIONS: Understanding the effects of the menstrual cycle and hormonal contraception on musculoskeletal health and performance will inform contraceptive choices for physically active women to manage injury risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT05587920; https://classic.clinicaltrials.gov/ct2/show/NCT05587920. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50542.

Hormonal contraceptive use among women living with hypertension in sub-Saharan Africa: insights from 12 countries.

OBJECTIVES: Given the well-established link between hormonal contraceptives and hypertension risk, and the paucity of research on hormonal contraceptive use dynamics in this particular demographic, we hypothesize that there is a likelihood of low utilization of high-risk hormonal contraceptives among women living with hypertension in SSA. This study investigates the prevalence and factors associated with hormonal contraceptive use among women living with hypertension in the SSA. RESULTS: Only 18.5% of women living with hypertension used hormonal contraceptives. Hormonal contraceptive use was high among women with a higher level of education (aOR = 2.33; 95%CI: 1.73-3.14), those currently working (aOR = 1.38; 95%CI: 1.20-1.59), those who have heard about family planning on the radio (aOR = 1.27, 95%CI: 1.09-1.47), listened to the radio at least once a week (aOR = 1.29, 95%CI: 1.10-1.51), and those residing in rural areas (aOR = 1.32; 95%CI: 1.14-1.54). Conversely, women aged 45-49 exhibited a substantial decrease in the odds of hormonal contraceptive use (aOR = 0.23, 95%CI: 0.14-0.38) compared to younger women (15-19 years). Likewise, the odds of HCU were low among cohabiting (aOR = 0.66; 95%CI: 0.48-0.89) and previously married women (aOR = 0.67; 95%CI: 0.50-0.91) than never married women.

Perception about benefits and risks related to combined hormonal contraceptives use in women with Lynch syndrome.

OBJECTIVE: Lynch syndrome (LS) is a hereditary condition associated with an increased risk of colorectal and endometrial cancer. This study aimed to assess the knowledge, attitudes, and beliefs of women with LS regarding combined hormonal contraceptive (CHC) use compared to a control group of healthy women. METHODS: Pre-menopausal women with LS (n = 43) and an age-matched control group of healthy women (n = 128) participated in this prospective, cross-sectional study (NCT05909410). Participants completed an electronic questionnaire evaluating perceptions of CHC use and its impact on various cancers, medical conditions, and symptoms. Statistical analysis compared responses between the two groups, with reported p-values. RESULTS: Women with LS were less likely to use CHCs compared to the control group (p = 0.03) and had a more negative perception of CHCs' impact on colorectal cancer (p = 0.023) and endometrial cancer (p = 0.028). Limited knowledge was observed in both groups regarding the protective effects of CHCs against colorectal and ovarian cancer. Perceptions of CHC use and its impact on symptoms and chronic diseases did not significantly differ between the groups (p > 0.05). CHC use was not associated with greater awareness of the protective effect against colorectal (p = 0.89) and endometrial cancer (p = 0.47), but it was associated with a desire for contraception (OR 21.25; 95% CI 1.16 to 388.21; p = 0.039). CONCLUSION: This study highlights contrasting perceptions of CHCs and their implications in oncology between women with LS and healthy women. Tailored counselling and support strategies are crucial for empowering women with LS to make informed decisions about their gynaecologic health.

This study illuminates divergent perceptions of combined hormonal contraceptives and their oncological implications between women with Lynch syndrome and healthy women.Tailored counseling and supportive strategies are essential for empowering women with Lynch syndrome to make informed decisions regarding their gynecologic health.

Leveraging web search data in Germany to identify unmet needs of contraceptives on a population-based level: A longitudinal retrospective study.

BACKGROUND: There are a variety of possible contraceptives available. While medical advice is an important resource for selecting the individual contraceptive, previous research has shown that the Internet has become an increasingly important source of health care information. OBJECTIVES: This study aims to identify key trends in contraception-related web searches in Germany and thus allows conclusions about preferences and unmet needs with regard to pregnancy prevention. DESIGN: Longitudinal retrospective study. METHODS: Google Ads Keyword Planner was used to identify contraception-related keywords and their search volume in Germany and all federal states between 2018 and 2021. The keywords were categorized based on gender, hormonal/non-hormonal, and different contraceptive methods. Search volume and categories were analyzed for temporal trends, regional differences, and underlying socioeconomic variables. RESULTS: The 1481 contraception-related keywords corresponded to 15,081,760 searches. In total, a 56% increase in searches/100,000 inhabitants was observed. Highest mean search volume was observed in categories "woman," "woman/non-hormonal" and "woman/non-hormonal/barrier," respectively, and in the federal state Hamburg, while the lowest was seen in North Rhine-Westphalia. CONCLUSION: The increase in search volume reflects a high interest in contraception, particularly in non-hormonal female methods. This stands in contrast to the limited number of effective non-hormonal contraceptives available and points to an unmet need. In addition, the low search volume for male contraceptives demonstrates gender-specific responsibilities regarding family planning in German society.

Analyzing Google search volume to identify preferences and unmet needs in contraception in German societyContraception is a topic that occupies many people in their daily lives. There is a wide range of different contraceptives available. The decision for a particular contraceptive can be made with the help of a consultation with a gynecologist or through other sources, such as the Internet. Research has shown that the Internet has become an important source for obtaining health information. This study aims to identify key trends in contraception-related web searches in Germany and thus allows conclusions about preferences and unmet needs with regard to pregnancy prevention. Google Ads Keyword Planner was used to identify contraception-related keywords and their search volume in Germany and all federal states between 2018 and 2021. The keywords were assigned to different categories based on whether the woman or the man uses the contraceptive, whether the contraceptive methods contain hormones or no hormones, and which exact contraceptive methods are associated with the search term. The search volume was analyzed in terms of trends over time, regional differences in Germany and socioeconomic variables. A 56% increase in searches per 100,000 inhabitants was observed. The highest mean search volume was observed in the category woman, followed by female non-hormonal contraceptives and within that category, the contraceptive method "barrier." The study shows that there is a high interest in contraception, especially in non-hormonal female contraceptives. These results contrast with the limited number of non-hormonal and effective contraceptive methods available. In addition, the low search volume in the category man shows that women are the main responsible party in terms of contraception in German society.

The oral contraceptive cycle and its influences on maximal and submaximal endurance parameters in elite handball players.

The usage of the oral contraceptive pill is widespread among athletes of various levels. However, there is limited knowledge on how the intake of the pill alters the submaximal and maximal endurance parameters between the oral contraceptive phases. Therefore, the aim of this study was to examine potential differences between the pill intake and withdrawal phase on endurance-related parameters in first-division handball players. In total, 15 female team handball players performed two graded exercise tests until volitional exhaustion on a motorized treadmill. Tests were performed during the pill intake (days 16-17) and withdrawal phase (day 2-3). Throughout the test, respiratory gases were measured breath-by-breath, and the heart rate was measured continuously. Before and after the graded exercise test, blood samples were obtained in order to assess the blood lactate concentration. Before each test, venous blood samples were taken to determine endogenous sex hormone levels. Ventilatory parameters (V˙O2, V˙CO2, and V˙E, and respiratory equivalents for V˙O2 and V˙CO2) were measured, and the oxidation of fat and carbohydrates was calculated. A paired-sample t-test was used to assess differences between the two time points, and the significance was accepted as p < 0.050. Significant differences with lower values during the consumption phase were found for absolute (mean difference ± SD: 88 ± 131 mL∙min-1; p = 0.021) and relative V˙O2peak (mean difference ± SD: 1 ± 2 mL∙min-1∙kg-1; p = 0.012). Higher values during the consumption phase were found for submaximal respiratory equivalents for V˙O2 (mean difference ± SD: -1.1 ± 1.7; p = 0.028) and V˙CO2 (mean difference ± SD: -0.9 ± 1.5; p = 0.032). No differences were found for all other parameters, including differences for endogenous sex hormones (p > 0.050). The results of the current study suggest only marginal and physiologically insignificant differences in endurance-related parameters between oral contraceptive phases.

Estetrol/drospirenone versus 17α-ethinylestradiol/drospirenone: An extended one generation test to evaluate the endocrine disruption potential on zebrafish (Danio rerio).

Combined oral contraceptives, comprising of both an oestrogen and a progestin component, are released in aquatic environments and potentially pose a risk to aquatic wildlife by their capacity to disrupt physiological mechanisms. In this study, the endocrine disruptive potential of two mixtures, 17α-ethinylestradiol (EE2), a synthetic oestrogen, or estetrol (E4), a natural oestrogen, with the progestin drospirenone (DRSP) have been characterised in three generations of zebrafish, according to an adapted Medaka Extended One Generation Reproduction Test. Zebrafish (Danio rerio) were exposed to a range of concentrations of EE2/DRSP and E4/DRSP (∼1×, ∼3×, ∼10× and ∼30× predicted environmental concentration, PEC). Survival, growth, hatching success, fecundity, fertilisation success, vitellogenin (VTG), gonad histopathology, sex differentiation, and transcriptional analysis of genes related to gonadal sex steroid hormones synthesis were assessed. In the F0 generation, exposure to EE2/DRSP at ∼10 and ∼30× PEC decreased fecundity and increased male VTG concentrations. The highest concentration of EE2/DRSP also affected VTG concentrations in female zebrafish and the expression of genes implicated in steroid hormones synthesis. In the F1 generation, sex determination was impaired in fish exposed to EE2/DRSP at concentrations as low as ∼3× PEC. Decreased fecundity and fertility, and abnormal gonadal histopathology were also observed. No effects were observed in the F2 generation. In contrast, E4/DRSP induced only minor histopathological changes and an increase in the proportion of males, at the highest concentration tested (∼30× PEC) in the F1 generation and had no effect on hatching success of F2 generation. Overall, this study suggests that the combination E4/DRSP has a more favourable environmental profile than EE2/DRSP.

Major depression associated with a levonorgestrel-releasing intrauterine system mimicking frontotemporal dementia: a case report.

This case illustrates the adverse cognitive and affective effects associated with the use of an intrauterine hormonal contraceptive, which could be confused with symptoms of early onset dementia. We present a case of a 42-year-old woman diagnosed with seronegative spondyloarthropathy who subsequently developed anxiety and depressive symptoms after the implantation of a Levonorgestrel-Releasing Intrauterine System (LNG-IUS). Three years later, she began to experience memory and attentional failures, refractory pain, and severe depression. The progression of psychiatric symptoms led to a diagnosis of bipolar affective disorder and treatment with antidepressants and anxiolytics. Due to cognitive and psychiatric symptoms, autoimmune encephalitis was considered, but no improvement was shown with treatment. Early onset dementia was suspected, and a brain PET scan revealed frontal lobe hypometabolism. An adverse effect of LNG-IUS was considered; after its removal, mood and cognitive function improvements were observed. This case report emphasizes the importance of considering organic causes of unexplained psychiatric manifestations and highlights the potential impact of hormonal interventions on mental health.

Social-psychological determinants of hormonal contraceptive use intentions among adolescent girls in the Bono East Region of Ghana.

Introduction: The correct and consistent use of hormonal contraceptive (HC) methods by sexually active adolescent girls can prevent pregnancy and avert the health and social consequences of unwanted pregnancy for both the mother and her child. Despite these benefits, research shows that HC use is rather low among adolescent girls globally and especially among those in low and middle-income countries. This study was carried out to assess the social-psychological determinants of HC use intentions among adolescent girls and young women. Methods: A cross-sectional survey was conducted among 1,203 young women aged 15-24 years from 70 communities within the Kintampo North Municipality and Kintampo South District in the Bono-East Region of Ghana from April 2021 to September 2021. Multiple linear regression analysis was used to identify factors associated with the intention to use HC among the entire sample of 1,203 respondents and among two sub-samples of young women based on HC use experience. Results: Attitude toward personal HC use (ß = 0.268; p < 0.001), self-efficacy toward access and use of HC (ß = 0.341; p < 0.001), and HC use experience (ß = 0.647; p < 0.001) were found to be significant and unique correlates of HC use intention among the entire sample of adolescent girls. Attitude toward personal HC use and self-efficacy toward access and use of HC were also associated with HC use intention in the two sub samples significantly (p's < 0.001). In addition, among participants with no HC experience, being a Christian as opposed to participants that affiliate themselves with Islam, Traditional religion or being non-religious positively predicts future HC use (ß = 0.230; p < 0.01). Conclusion: Our results demonstrate that different groups of adolescent girls need different interventions, focusing on different determinants for the motivation to use HC. Comprehensive sexuality education, informing all adolescent girls about the personal benefits of HC use and enhancing their skills in accessing and using HCs, can support their HC use intentions to promote their reproductive health and general wellbeing.

The influence of the menstrual cycle and hormonal contraceptives on cardiorespiratory fitness in physically active women: A systematic review and meta-analysis.

Objective: To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on V˙O2max in physically active women. Methods: This systematic review and meta-analysis conforms to the PRISMA statement guidelines. Four (sub-)meta-analyses were performed. Two focused on longitudinal studies examining the same women several times to compare the V˙O2max during the different menstrual phases or oral contraceptive (OC) use and withdrawal. Two meta-analyses examined if there is a difference in V˙O2max between OC users and normally menstruating women by analyzing cross-sectional studies assigning physically active women to one of these two groups as well as intervention-based studies (cross-over studies, randomized controlled trials considering only the data of the intervention group) comparing women intra-individually with and without OCs. Results: Nine of the included studies (107 women) evaluated the influence of the MC, five studies (69 women) the impact of OCs on V˙O2max, and six studies investigated both topics (88 women). A mean difference of V˙O2max -0.03 ml/kg/min (95%CI -1.06 to 1.01) between the early follicular and luteal menstrual phase was observed. Between the active and inactive phases of OCs, a mean difference of -0.11 ml/kg/min (95%CI -2.32 to 2.10) was found. The inter-individual comparison of naturally menstruating women and OC users showed a mean difference in V˙O2max of 0.23 ml/kg/min (95% CI -2.33 to 2.79) in favor of OC use. The intra-individual comparison of the same women showed a mean decrease in V˙O2max of -0.84 ml/kg/min (95% CI -2.38 to 0.70) after a new start with OCs. Conclusions: Our meta-analyses showed no effects of the MC or the OCs on V˙O2max. More high-quality studies are needed determining the MC phases more precisely, including OCs with the current standard formulations and comparing the influence of different progestins.

The impact of natural menstrual cycle and oral contraceptive pill phase on substrate oxidation during rest and acute submaximal aerobic exercise.

Previous research has identified sex differences in substrate oxidation during submaximal aerobic exercise including a lower respiratory exchange ratio (RER) in females compared with males. These differences may be related to differences in sex hormones. Our purpose was to examine the impact of the natural menstrual cycle (NAT) and second- and third-generation oral contraceptive pill (OCP2 and OCP3) cycle phases on substrate oxidation during rest and submaximal aerobic exercise. Fifty female participants (18 NAT, 17 OCP2, and 15 OCP3) performed two experimental trials that coincided with the low (i.e., nonactive pill/early follicular) and the high hormone (i.e., active pill/midluteal) phase of their cycle. RER and carbohydrate and lipid oxidation rates were determined from gas exchange measurements performed during 10 min of supine rest, 5 min of seated rest, and two 8-min bouts of submaximal cycling exercise at ∼40% and ∼65% of peak oxygen uptake (V̇o2peak). For all groups, there were no differences in RER between the low and high hormone phases during supine rest (0.73 ± 0.05 vs. 0.74 ± 0.05), seated rest (0.72 ± 0.04 vs. 0.72 ± 0.04), exercise at 40% (0.77 ± 0.04 vs. 0.78 ± 0.04), and 65% V̇o2peak (0.85 ± 0.04 vs. 0.86 ± 0.03; P > 0.19 for all). Similarly, carbohydrate and lipid oxidation rates remained largely unchanged across phases during both rest and exercise, apart from higher carbohydrate oxidation in NAT vs. OCP2 at 40% V̇o2peak (P = 0.019) and 65% V̇o2peak (P = 0.001). NAT and OCPs do not appear to largely influence substrate oxidation at rest and during acute submaximal aerobic exercise.NEW & NOTEWORTHY This study was the first to examine the influence of NAT and two generations of OCPs on substrate oxidation during rest and acute submaximal aerobic exercise. We reported no differences across cycle phases or groups on RER, and minimal impact on carbohydrate or lipid oxidation apart from an increase in carbohydrate oxidation in NAT compared with OCP2 during exercise. Based on these findings, NAT/OCP phase controls may not be necessary in studies investigating substrate oxidation.

International society of sports nutrition position stand: nutritional concerns of the female athlete.

Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Female athletes have unique and unpredictable hormone profiles, which influence their physiology and nutritional needs across their lifespan. To understand how perturbations in these hormones affect the individual, we recommend that female athletes of reproductive age should track their hormonal status (natural, hormone driven) against training and recovery to determine their individual patterns and needs and peri and post-menopausal athletes should track against training and recovery metrics to determine the individuals' unique patterns. 2. The primary nutritional consideration for all athletes, and in particular, female athletes, should be achieving adequate energy intake to meet their energy requirements and to achieve an optimal energy availability (EA); with a focus on the timing of meals in relation to exercise to improve training adaptations, performance, and athlete health. 3. Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent, therefore we recommend first ensuring athletes meet their carbohydrate needs across all phases of the menstrual cycle. Secondly, tailoring carbohydrate intake to hormonal status with an emphasis on greater carbohydrate intake and availability during the active pill weeks of oral contraceptive users and during the luteal phase of the menstrual cycle where there is a greater effect of sex hormone suppression on gluconogenesis output during exercise. 4. Based upon the limited research available, we recommend that pre-menopausal, eumenorrheic, and oral contraceptives using female athletes should aim to consume a source of high-quality protein as close to beginning and/or after completion of exercise as possible to reduce exercise-induced amino acid oxidative losses and initiate muscle protein remodeling and repair at a dose of 0.32-0.38 g·kg-1. For eumenorrheic women, ingestion during the luteal phase should aim for the upper end of the range due to the catabolic actions of progesterone and greater need for amino acids. 5. Close to the beginning and/or after completion of exercise, peri- and post-menopausal athletes should aim for a bolus of high EAA-containing (~10 g) intact protein sources or supplements to overcome anabolic resistance. 6. Daily protein intake should fall within the mid- to upper ranges of current sport nutrition guidelines (1.4-2.2 g·kg-1·day-1) for women at all stages of menstrual function (pre-, peri-, post-menopausal, and contraceptive users) with protein doses evenly distributed, every 3-4 h, across the day. Eumenorrheic athletes in the luteal phase and peri/post-menopausal athletes, regardless of sport, should aim for the upper end of the range. 7. Female sex hormones affect fluid dynamics and electrolyte handling. A greater predisposition to hyponatremia occurs in times of elevated progesterone, and in menopausal women, who are slower to excrete water. Additionally, females have less absolute and relative fluid available to lose via sweating than males, making the physiological consequences of fluid loss more severe, particularly in the luteal phase. 8. Evidence for sex-specific supplementation is lacking due to the paucity of female-specific research and any differential effects in females. Caffeine, iron, and creatine have the most evidence for use in females. Both iron and creatine are highly efficacious for female athletes. Creatine supplementation of 3 to 5 g per day is recommended for the mechanistic support of creatine supplementation with regard to muscle protein kinetics, growth factors, satellite cells, myogenic transcription factors, glycogen and calcium regulation, oxidative stress, and inflammation. Post-menopausal females benefit from bone health, mental health, and skeletal muscle size and function when consuming higher doses of creatine (0.3 g·kg-1·d-1). 9. To foster and promote high-quality research investigations involving female athletes, researchers are first encouraged to stop excluding females unless the primary endpoints are directly influenced by sex-specific mechanisms. In all investigative scenarios, researchers across the globe are encouraged to inquire and report upon more detailed information surrounding the athlete's hormonal status, including menstrual status (days since menses, length of period, duration of cycle, etc.) and/or hormonal contraceptive details and/or menopausal status.

Women's attitudes about combined hormonal contraception (CHC) - induced menstrual bleeding changes - influence of personality traits in an Italian clinical sample.

OBJECTIVES: We investigated the attitudes to change the frequency of menstrual bleeding by using combined hormonal contraception (CHC). Personality characteristics were also explored. METHODS: We conducted a cross-sectional study in two university hospitals in northern Italy. Current, past and never CHC users (n = 545; age 18-44 years) completed a self-administered semi-structured questionnaire and the Ten-Item Personality Inventory (TIPI). RESULTS: Forty-five percent of responders (n = 301) would prefer to change their bleeding frequency by using CHC. A flexible regimen was the preferred choice (n = 80; 33%) followed by extended regimens to bleed every 3 months (n = 54; 22%) or to never bleed (n = 43; 18%). The main positive reasons were to avoid dysmenorrhea (43%) and have more freedom in sexual (36%) and active (35%) life, whereas the main reason for a negative attitude was 'menstrual rhythm is natural' (59%). Age had a significant influence on women's willingness to change menstrual frequency by using CHC [>39 years (57%), 30-39 years (31%) and <30 years (46%)] (χ2: 9.1; p = 0.01). Never users significantly reported a more negative attitude (71%) in comparison with past (51%) and current users (49%) (χ2: 18.7; p = 0.001). Personality traits played a role, with higher scores of openness (p = 0.005) and extraversion (p = 0.001) in women with a positive attitude. CONCLUSIONS: Almost half of our study sample reported a preference for changing their menstrual pattern by using CHC. Flexibility was the preferred choice across age and use of CHC. Personality characteristics (openness and extroversion) might influence attitudes toward CHC-induced menstrual bleeding changes.

Oral contraceptives and cognition: A systematic review.

Oral contraceptives (OCs) are widely used. While the physical impacts of OCs have been well researched, there is increasing interest on potential impacts of OCs on brain, behaviour and cognition. We systematically reviewed the literature to determine the influence of OCs on cognition, including neurocognition, social cognition and emotional processing. Inclusionary criteria were: (a) premenopausal females taking OCs; (b) a control group of naturally cycling women or OCs users in their inactive (i.e. 'sugar pill') phase; and (c) at least one measure of performance on a neurocognitive or social cognitive task. The systematic review found that OC use was associated with some differences in performance on all cognitive domains examined (with the exception of basic auditory attention and psychomotor performance). Several factors were identified that are likely to modulate the way OCs influence cognition, including task related factors, OC type and control group characteristics. Directions for future research are highlighted.

Oral contraceptives in the central nervous system: Basic pharmacology, methodological considerations, and current state of the field.

Millions of women around the world use combined oral contraceptives (OCs), yet surprisingly little is known about their central nervous system (CNS) effects. This article provides a short overview of the basic pharmacology of OCs, emphasizing features that may be relevant to understanding their effects in the CNS. Historical and recent findings from studies of cognitive function, mood, and negative affect (depressive changes under OC use) are then reviewed. We also present data from an archival dataset from our own laboratory in which we explore dysphoric changes in women using four generations of contraceptive progestins. Current data in the field are consistent with a modest effect of OC use on CNS variables, but conclusions based on current findings must be made very cautiously because of multiple methodological issues in many published studies to date, and inconsistencies in the findings. Directions for future research over the next 10 years are suggested. (150 words).

Hormonal Contraceptive Use and Risk of Depression Among Young Women With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Women with attention-deficit/hyperactivity disorder (ADHD) have an increased risk of becoming teenage mothers. Adverse effects of hormonal contraception (HC), including depression, may affect adherence to user-dependent contraception and increase the risk for unplanned pregnancies and teenage births in women with ADHD. The current study analyzed whether girls and young women with ADHD are at increased risk for depression during HC use compared with women without ADHD. METHOD: A linkage of Swedish national registers covering 29,767 girls and young women with ADHD aged 15 to 24 years and 763,146 without ADHD provided measures of ADHD and depression diagnoses (International Classification of Diseases [ICD] code) and prescription of stimulant medication, HC, and antidepressant medication (Anatomical Therapeutic Chemical [ATC] code). Cox regression models applying an interaction term (ADHD diagnosis × HC use) evaluated the excess risk of HC-induced depression in women with ADHD. RESULTS: Women with ADHD had a 3-fold higher risk of developing depression, irrespective of HC use (adjusted hazard ratio [aHR] = 3.69, 95% CI = 3.60-3.78). Oral combined HC users with ADHD had a 5 times higher risk of depression compared with women without ADHD who were not using oral combined HC (aHR = 5.19, 95% CI = 4.94-5.47), and a 6 times higher risk in comparison with women without ADHD who were on oral combined HC (aHR = 6.10 (95% CI = 5.79-6.43). The corresponding risk of depression in women with ADHD who used a progestogen-only pill (aHR = 5.00, 95% CI = 4.56-5.49). The risk of developing depression when using non-oral HC was similarly moderately increased in both groups. CONCLUSION: Girls and young women with ADHD have an increased risk of developing depression when using oral HC compared with their unaffected peers. Information on risks with HCs as well as potential benefits with long-acting reversible contraceptives needs to be an integrated part of the shared decision making and contraception counseling for young women with ADHD.

Effects of oral contraceptives on spatial cognition depend on pharmacological properties and phase of the contraceptive cycle.

The central nervous system effects of oral contraceptives (OCs) are not well-documented. In a set of 3 studies, we investigated a specific cognitive function, mental rotation, in healthy women currently using OCs for contraceptive purposes (n = 201) and in medication-free controls not using OCs (n = 44). Mental rotation was measured using a well-standardized and extensively validated psychometric test, the Vandenberg Mental Rotations Test (MRT). In an initial study (Study 1), current OC users (n = 63) were tested during the active or inactive phases of the contraceptive cycle in a parallel-groups design. Studies 2 and 3 were based on an archival dataset (n = 201 current OC users) that consisted of data on the MRT collected in real-time over a 30-year period and compiled for purposes of the present work. The OCs were combined formulations containing ethinyl estradiol (10-35 ug/day) plus a synthetic progestin. All 4 families of synthetic progestins historically used in OCs were represented in the dataset. Cognitive performance was evaluated during either active OC use ('active phase') or during the washout week of the contraceptive cycle ('inactive phase') when OC steroids are not used. The results showed a significant phase-of-cycle (POC) effect. Accuracy on the MRT was mildly diminished during the active phase of OC use, while scores on verbal fluency and speeded motor tasks were modestly improved. The POC effect was most evident in women using OCs that contained first- or second-generation progestins (the estrane family of progestins or OCs containing levonorgestrel), but not in women using OCs containing recently developed progestins and lower doses of ethinyl estradiol. Using independently established ratings of the estrogenic, androgenic, and progestogenic intensities of the different OC formulations, each brand of OC was classified according to its distinct endocrine profile. Multiple regression revealed that the effects of OC use on the MRT could be predicted based on the estrogenic strength of the contraceptives used. Estrogenic potency, not androgenic or anti-androgenic effects of the OC pill, may underlie the effects of OC usage on spatial cognition.

Effects of an Oral Contraceptive on Dynamic Brain States and Network Modularity in a Serial Single-Subject Study.

Hormonal contraceptive drugs are used by adolescent and adult women worldwide. Increasing evidence from human neuroimaging research indicates that oral contraceptives can alter regional functional brain connectivity and brain chemistry. However, questions remain regarding static whole-brain and dynamic network-wise functional connectivity changes. A healthy woman (23 years old) was scanned every day over 30 consecutive days during a naturally occurring menstrual cycle and again a year later while using a combined hormonal contraceptive. Here we calculated graph theory-derived, whole-brain, network-level measures (modularity and system segregation) and global brain connectivity (characteristic path length) as well as dynamic functional brain connectivity using Leading Eigenvector Dynamic Analysis and diametrical clustering. These metrics were calculated for each scan session during the serial sampling periods to compare metrics between the subject's natural and contraceptive cycles. Modularity, system segregation, and characteristic path length were statistically significantly higher across the natural compared to contraceptive cycle scans. We also observed a shift in the prevalence of two discrete brain states when using the contraceptive. Our results suggest a more network-structured brain connectivity architecture during the natural cycle, whereas oral contraceptive use is associated with a generally increased connectivity structure evidenced by lower characteristic path length. The results of this repeated, single-subject analysis allude to the possible effects of oral contraceptives on brain-wide connectivity, which should be evaluated in a cohort to resolve the extent to which these effects generalize across the population and the possible impact of a year-long period between conditions.