Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.

PURPOSE: Midostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants. METHODS: Using sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2. RESULTS: In Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3-4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48-49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7-10% increase in AUC of EES; and a 19% increase in Cmax and 29-42% increase in AUC of LVG. Midostaurin 50 mg twice daily for 28 days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported. CONCLUSION: Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

Continuous 17α-ethinylestradiol exposure impairs the sperm quality of marine medaka (Oryzias melastigma).

17α-ethinylestradiol (EE2) is an anthropogenic estrogen that is widely used for hormone therapy and oral contraceptives. It was reported that EE2 exposure induced reproductive impairments through processes affecting reproduction behavior and inducing ovotestis. However, the effects of continuous EE2 exposure on the reproductive performance remain largely unknown. In this study, adult marine medaka fish (Oryzias melastigma) were exposed to EE2 (85 ng/L) for one (F0) and two (F1) generations. Our results indicate that continuous EE2 exposure reduced fecundity and sperm motility. The testicular transcriptome, followed by bioinformatic analysis revealed the dysregulation of pathways related to steroidogenesis, sperm motility, and reproductive system development. Collectively, our findings indicate that continuous EE2 exposure directly affected sperm quality via the alteration of steroidogenesis and dysregulation of reproductive system development. The identified key factors including DNM1, PINK1, PDE7B, and SLC12A7 can serve as biomarkers to assess EE2-reduced sperm motility.

Imaging the human brain on oral contraceptives: A review of structural imaging methods and implications for future research goals.

Worldwide over 150 million women use oral contraceptives (OCs), which are the most prescribed form of contraception in both the United States and in European countries. Sex hormones, such as estradiol and progesterone, are important endogenous hormones known for shaping the brain across the life span. Synthetic hormones, which are present in OCs, interfere with the natural hormonal balance by reducing the endogenous hormone levels. Little is known how this affects the brain, especially during the most vulnerable times of brain maturation. Here, we review studies that investigate differences in brain gray and white matter in women using OCs in comparison to naturally cycling women. We focus on two neuroimaging methods used to quantify structural gray and white matter changes, namely structural MRI and diffusion MRI. Finally, we discuss the potential of these imaging techniques to advance knowledge about the effects of OCs on the brain and wellbeing in women.

The effect of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo monocyte TNFα release following treatment with lipopolysaccharide and hyperthermia.

PURPOSE: Investigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release following treatment with lipopolysaccharide (LPS) and hyperthermia. METHODS: Twenty-seven participants (9 men, 9 eumenorrheic women (MC) and 9 women taking an oral contraceptive pill (OC)) completed three trials. Men were tested on 3 occasions over 6 weeks; MC during early-follicular, ovulation, and mid-luteal phases; OC during the pill and pill-free phase. Intestinal permeability was assessed following a 4-hour dual sugar absorption test (lactulose: rhamnose). Venous blood was collected each trial and stimulated with 100 µg·mL-1 LPS before incubation at 37 °C and 40 °C and analysed for TNFα via ELISA. RESULTS: L:R ratio was higher in OC than MC (+0.003, p = 0.061) and men (+0.005, p = 0.007). Men had higher TNFα responses than both MC (+53 %, p = 0.004) and OC (+61 %, p = 0.003). TNFα release was greater at 40 °C than 37 °C (+23 %, p < 0.001). CONCLUSIONS: Men present with lower resting intestinal barrier permeability relative to women regardless of OC use and displayed greater monocyte TNFα release following whole blood treatment with LPS and hyperthermia. Oral contraceptive users had highest intestinal permeability however, neither permeability or TNFα release were impacted by the pill cycle. Although no statistical effect was seen in the menstrual cycle, intestinal permeability and TNFα release were more variable across the phases.

Oral contraceptives and stroke: Foes or friends.

Incidents of strokes are increased in young women relative to young men, suggesting that oral contraceptive (OC) use is one of the causes of stroke among young women. Long-term exposures to the varying combinations of estrogen and progestogen found in OCs affect blood clotting, lipid and lipoprotein metabolism, endothelial function, and de novo synthesis of neurosteroids, especially brain-derived 17ß-estradiol. The latter is essential for neuroprotection, memory, sexual differentiation, synaptic transmission, and behavior. Deleterious effects of OCs may be exacerbated due to comorbidities like polycystic ovary syndrome, sickle cell anemia, COVID-19, exposures to endocrine disrupting chemicals, and conventional or electronic cigarette smoking. The goal of the current review is to revisit the available literature regarding the impact of OC use on stroke, to explain possible underlying mechanisms, and to identify gaps in our understanding to promote future research to reduce and cure stroke in OC users.

Blood oxidative stress biomarkers in women: influence of oral contraception, exercise, and N-acetylcysteine.

PURPOSE: To compare physiological responses to submaximal cycling and sprint cycling performance in women using oral contraceptives (WomenOC) and naturally cycling women (WomenNC) and to determine whether N-acetylcysteine (NAC) supplementation mediates these responses. METHODS: Twenty recreationally trained women completed five exercise trials (i.e., an incremental cycling test, a familiarisation trial, a baseline performance trial and two double-blind crossover intervention trials). During the intervention trials participants supplemented with NAC or a placebo 1 h before exercise. Cardiopulmonary parameters and blood biochemistry were assessed during 40 min of fixed-intensity cycling at 105% of gas-exchange threshold and after 1-km cycling time-trial. RESULTS: WomenOC had higher ventilation (ß [95% CI] = 0.07 L·min-1 [0.01, 0.14]), malondialdehydes (ß = 12.00 mmol·L-1 [6.82, 17.17]) and C-reactive protein (1.53 mg·L-1 [0.76, 2.30]), whereas glutathione peroxidase was lower (ß =  22.62 mU·mL-1 [- 41.32, - 3.91]) compared to WomenNC during fixed-intensity cycling. Plasma thiols were higher at all timepoints after NAC ingestion compared to placebo, irrespective of group (all p < 0.001; d = 1.45 to 2.34). For WomenNC but not WomenOC, the exercise-induced increase in malondialdehyde observed in the placebo trial was blunted after NAC ingestion, with lower values at 40 min (p = 0.018; d = 0.73). NAC did not affect cycling time-trial performance. CONCLUSIONS: Blood biomarkers relating to oxidative stress and inflammation are elevated in WomenOC during exercise. There may be an increased strain on the endogenous antioxidant system during exercise, since NAC supplementation in WomenOC did not dampen the exercise-induced increase in malondialdehyde. Future investigations should explore the impact of elevated oxidative stress on exercise adaptations or recovery from exercise in WomenOC.

No Differences in Value-Based Decision-Making Due to Use of Oral Contraceptives.

Fluctuating ovarian hormones have been shown to affect decision-making processes in women. While emerging evidence suggests effects of endogenous ovarian hormones such as estradiol and progesterone on value-based decision-making in women, the impact of exogenous synthetic hormones, as in most oral contraceptives, is not clear. In a between-subjects design, we assessed measures of value-based decision-making in three groups of women aged 18 to 29 years, during (1) active oral contraceptive intake (N = 22), (2) the early follicular phase of the natural menstrual cycle (N = 20), and (3) the periovulatory phase of the natural menstrual cycle (N = 20). Estradiol, progesterone, testosterone, and sex-hormone binding globulin levels were assessed in all groups via blood samples. We used a test battery which measured different facets of value-based decision-making: delay discounting, risk-aversion, risk-seeking, and loss aversion. While hormonal levels did show the expected patterns for the three groups, there were no differences in value-based decision-making parameters. Consequently, Bayes factors showed conclusive evidence in support of the null hypothesis. We conclude that women on oral contraceptives show no differences in value-based decision-making compared to the early follicular and periovulatory natural menstrual cycle phases.

Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome.

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.

The acute effect of the menstrual cycle and oral contraceptive cycle on measures of body composition.

PURPOSE: This study aimed to investigate the effect of fluctuating female hormones during the menstrual cycle (MC) and oral contraceptive (OC) cycle on different measures of body composition. METHODS: Twenty-two women with a natural MC and thirty women currently taking combined monophasic OC were assessed over three phases of the menstrual or oral contraceptive cycle. Body weight, skinfolds, bioelectric impedance analysis (BIA), ultrasound, dual-energy X-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT) measurements were performed to assess body composition. Urine specific gravity (USG) was measured as an indication of hydration, and serum oestradiol and progesterone were measured to confirm cycle phases. RESULTS: Five participants with a natural MC were excluded based on the hormone analysis. For the remaining participants, no significant changes over the MC and OC cycle were found for body weight, USG, skinfolds, BIA, ultrasound and pQCT measures. However, DXA body fat percentage and fat mass were lower in the late follicular phase compared to the mid-luteal phase of the MC, while for the OC cycle, DXA body fat percentage was higher and lean mass lower in the early hormone phase compared with the late hormone phase. CONCLUSION: Our findings suggest that assessment of body fat percentage through BIA and skinfolds may be performed without considering the MC or OC cycle. Body adiposity assessment via DXA, however, may be affected by female hormone fluctuations and therefore, it may be advisable to perform repeat testing using DXA during the same phase of the MC or OC cycle.

The modulation of social behavior and empathy via oral contraceptives and female sex hormones.

Oral contraceptives (OC) and endogenous female sex hormones in naturally cycling women (NC) are related to a wide range of psychological variables (eg, cognition and affect). Little research on social behavior has been done. One study documented a tendency towards more prosocial behavior in NC than OC women, but the underlying neuroendocrine mechanisms remain unknown. The sex hormones progesterone and estradiol are potential candidates. We analyzed social decision-making and social behavior in 83 healthy women (38 OC and 45 NC) via the Social Value Orientation (SVO) and in real social interactions within a paradigm adapted from behavioral economics. We also measured empathy, and collected saliva samples to quantify the basal levels of estradiol and progesterone. Our analyses revealed higher levels of prosocial behavior and emotional empathy in NC than in OC women, a finding supported by higher levels of prosocial decisions in NC than OC women in the SVO. Regarding the underlying biological mechanisms, we detected lower progesterone levels in OC than NC women. Exploratory analyses revealed a negative correlation between progesterone and trust on the trend level. We found no correlations between estradiol and behavior. Our findings provide evidence that OC modulate social behavior and initial indications of a possible modulation by progesterone. Further research is needed to replicate our findings and extend them to other social behaviors.

Noninvasive detection of human dehydroepiandrosterone, progesterone and testosterone using LC-MS/MS revealed effects of birth control pills/devices and body weight on ovulatory prediction.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been increasingly used to measure steroids in human saliva. We studied the performance of a conventional LC-MS/MS for measuring dehydroepiandrosterone (DHEA), testosterone and progesterone in human saliva. These three steroids were co-extracted by liquid-liquid extraction and derivatized. Derivatives were resolved on a C18 column and quantified using an LC-MS/MS (AB Sciex API 2000) instrument. The assay's limits of quantification were 0.03 ng/mL for all three steroids. Inter-assay coefficients of variation were 16.6-18.8% (DHEA), 12.0-15.8% (testosterone), and 12.7-19.3% (progesterone). Assay linearity analysis showed R2 of 0.9926, 0.9750 and 0.9949 for DHEA, testosterone and progesterone, respectively. No carry-over between samplings was observed. An ion-enhancement effect of 11.6% for DHEA determination and ion-suppression effects of 13.9% and 20.7% for analysis of progesterone and testosterone, respectively, were determined. No interferences by 9 steroid analogs were detected. Spiked recoveries were 85.5% (DHEA), 86.5% (testosterone), and 92.6% (progesterone). Comparison with laboratory developed test (LDT)-LC-MS/MS methods by other New York State Department of Health certified laboratories revealed R2 = 0.9425 (DHEA, LC-MS/MS = 1.0267 LDT + 21.989), R2 = 0.9849 (testosterone, LC-MS/MS = 0.9447 LDT + 9.8037), and R2 = 0.9736 (progesterone, LC-MS/MS = 1.1196 LDT + 0.0985). Reference intervals for the 3 steroids in saliva for young males and females were estimated. Results of intra-individual salivary progesterone analysis indicated that caution should be exercised when using progesterone concentrations in predicting ovulation for females who are under treatment with birth control pills/devices or has body a weight of > 90 kg.

Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS.

OBJECTIVE: To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic). DESIGN: Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29). MATERIALS AND METHODS: Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes. RESULTS: Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P < 0.001). None of the analytes were significantly affected by Lifestyle, whereas the effects of Combined were similar to OCPs alone, although attenuated. Oxyntomodulin was significantly positively associated with the change in total ovarian volume (rs = 0.27; 95% CI: 0.03, 0.48; P = 0.03) and insulin sensitivity index (rs = 0.48; 95% CI: 0.27, 0.64; P < 0.001), and it was inversely correlated with change in area under the curve (AUC) glucose [rs = -0.38; 95% CI: -0.57, -0.16; P = 0.001]. None of the hormonal changes were associated with live birth, only Activin A was associated with ovulation (risk ratio per 1 ng/mL increase in change in Activin A: 6.0 [2.2, 16.2]; P < 0.001). CONCLUSIONS: In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth.

Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS.

Polycystic ovary syndrome (PCOS) is characterized by elevated androgen production and subclinical changes in cardiovascular and metabolic risk markers. Total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glucose, and fasting insulin appear to increase specifically in PCOS compared with fertile women. PCOS also confers an increased risk of cardiometabolic disease in later life. Novel biomarkers such as serum's cholesterol efflux capacity and blood-derived macrophage activation profile may assist in more accurately defining the cardiometabolic risk profile in these women. Aldosterone antagonists, androgen receptor antagonists, 5α-reductase inhibitors, and synthetic progestogens are used to reduce hyperandrogenism. Because increased insulin secretion enhances ovarian androgen production, short-term treatment with metformin and other hypoglycemic agents results in significant weight loss, favorable metabolic changes, and testosterone reduction. The naturally occurring inositols display insulin-sensitizing effects and may be also used in this context because of their safety profile. Combined oral contraceptives represent the drug of choice for correction of androgen-related symptoms. Overall, PCOS management remains focused on specific targets including assessment and treatment of cardiometabolic risk, according to disease phenotypes. While new options are adding to established therapeutic approaches, a sometimes difficult balance between efficacy and safety of available medications has to be found in individual women.

L-glutamine ameliorates adipose-hepatic dysmetabolism in OC-treated female rats.

Adipose dysfunction and inflammation with or without hepatic defects underlie metabolic obesity. Glutamine (GLU) improves glucoregulation and metabolic indices but its effects on adipose function and hepatic lipid deposition in estrogen-progestin oral contraceptive (EPOC) users are unknown. Therefore, we hypothesized that GLUT supplementation would protect against adipose dysfunction and excess hepatic lipid influx and deposition in EPOC-treated animals by suppressing adenosine deaminase/xanthine oxidase (ADA/XO) activity and improving glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defense. Female Wistar rats weighing 150-180 g were allotted into control, GLUT, EPOC and EPOC + GLUT groups (six rats/group). The groups received vehicle (distilled water, p.o.), GLUT (1 g/kg), EPOC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and EPOC plus GLUT, respectively, daily for 8 weeks. Results showed that the administration of EPOC caused glucose dysregulation and increased triglyceride-glucose index and visceral adiposity, but the body weight and liver weight were not affected. However, EPOC significantly decreased adipose lipid, G6PD and glutathione and increased glycogen synthesis, ADA, XO, uric acid, lipid peroxidation, lactate production and gamma-glutamyl transferase activity (GGT). On the other hand, EPOC increased hepatic lipid, ADA, XO, uric acid, lipid peroxidation and lactate production and decreased glycogen synthesis, G6PD and glutathione. Nevertheless, supplementation with glutamine attenuated these alterations. Collectively, the present results indicate that EPOC causes metabolically induced obesity which is associated with adipose dysfunction and hepatic metabolic disturbance. The findings also suggest that glutamine confers metabo-protection with corresponding improvement in adipose and hepatic metabolic function by suppression of ADA/XO activity and enhancement of G6PD-dependent antioxidant defense.

Blockade of mineralocorticoid receptor ameliorates oral contraceptive-induced insulin resistance by suppressing elevated uric acid and glycogen synthase kinase-3 instead of circulating mineralocorticoid.

Context: Estrogen-progestin combined oral contraceptive (COC) has been connected to mineralocorticoid receptor (MR) activation and adverse cardiometabolic events. We consequently hypothesised that insulin resistance (IR), hyperuricemia, and elevated circulating GSK-3 induced by COC is through activation of MR via mineralocorticoid and glucocorticoid pathways.Methods: Female Wistar rats aged 12 weeks received (po) vehicle and COC (1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel) with or without MR blocker (0.25 mg/kg spironolactone; Spl), daily for eight weeks.Results: Data showed that COC treatment led to increased IR, 1-hour postload glucose level, insulinemia, triglyceride/HDL-cholesterol ratio, total cholesterol/HDL-cholesterol ratio, uric acid, GSK-3, aldosterone, corticosterone values, impaired glucose tolerance and pancreatic ß-cell function. However, MR blockade by Spl ameliorated all these alterations except that of aldosterone.Conclusion: The results demonstrate that COC induces IR, hyperuricemia and high GSK-3 levels through activation of MR via glucocorticoid dependent pathway.

Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver.

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

UPA and LNG in emergency contraception: the information by EMA and the scientific evidences indicate a prevalent anti-implantation effect.

RATIONALE AND OBJECTIVES: Emergency contraceptives pills (ECPs) are described as drugs that work by either inhibiting or delaying ovulation without affecting implantation. In our opinion, as we aim at demonstrating, both EMA documents and the experimental papers indicate that they prevalently inhibit embryo-implantation. LNG-ECPs: literature: LNG-ECPs never prevent ovulation when are taken in the most fertile days (EMA-EPAR on ellaOne® p. 9, first table). Conversely, they prevent the formation of an adequate corpus luteum. When they are taken pre-ovulatory ovulations occur regularly, but pregnancies do not appear. Taken after ovulation, they seem ineffective in preventing pregnancies. UPA-ECPs: literature: EllaOne® prevents ovulation only when is taken in the first fertile day. Thereafter, its anti-ovulatory effect drops sharply and becomes insignificant (8%) 36 h before ovulation, in the most fertile days (Brache); its decreasing anti-ovulatory effect cannot explain a consistently high effectiveness in preventing pregnancies (≥80%) that does not decrease depending on which of the 5 d it is taken after unprotected intercourse. Besides, ovulation occurs regularly in 91.7% of women taking ellaOne® weekly, for eight consecutive weeks (EMA-CHMP-Assessment Report 'EMA/73099/2015': study HRA2914-554, p. 7). Lastly, Lira-Albarrán administered ellaOne® to women in the most fertile pre-ovulatory days: they had normal ovulation, but their endometrium, evaluated through samples obtained in the implantation window, became inhospitable: the expression of 1183 genes was exactly the opposite of that observed in the receptive pro-gestational endometrium. This agrees with information by EMA-CHMP-Assessment Report 'EMEA/261787/2009' (p. 8): after UPA administration 'the proteins necessary to begin and maintain pregnancy are not synthesized'. CONCLUSIONS: Emergency Contraceptives work prevalently by preventing embryo-implantation. People shall receive correct information.

On exercise thermoregulation in females: interaction of endogenous and exogenous ovarian hormones.

KEY POINTS: One in two female athletes chronically take a combined, monophasic oral contraceptive pill (OCP). Previous thermoregulatory investigations proposed that an endogenous rhythm of the menstrual cycle still occurs with OCP usage. Forthcoming large international sporting events will expose female athletes to hot environments differing in their thermal profile, yet few data exist on how trained women will respond from both a thermoregulatory and performance stand-point. In the present study, we have demonstrated that a small endogenous rhythm of the menstrual cycle still affects Tcore and also that chronic OCP use attenuates the sweating response, whereas behavioural thermoregulation is maintained. Furthermore, humid heat affects both performance and thermoregulatory responses to a greater extent than OCP usage and the menstrual cycle does. ABSTRACT: We studied thermoregulatory responses of ten well-trained ( V̇O2max , 57 ± 7 mL min-1  kg-1 ) women taking a combined, monophasic oral contraceptive pill (OCP) (≥12 months) during exercise in dry and humid heat, across their active OCP cycle. They completed four trials, each of resting and cycling at fixed intensities (125 and 150 W), aiming to assess autonomic regulation, and then a self-paced intensity (30-min work trial) to assess behavioural regulation. Trials were conducted in quasi-follicular (qF) and quasi-luteal (qL) phases in dry (DRY) and humid (HUM) heat matched for wet bulb globe temperature (WBGT) (27°C). During rest and exercise at 125 W, rectal temperature was 0.15°C higher in qL than qF (P = 0.05) independent of environment (P = 0.17). The onset threshold and thermosensitivity of local sweat rate and forearm blood flow relative to mean body temperature was unaffected by the OCP cycle (both P > 0.30). Exercise performance did not differ between quasi-phases (qF: 268 ± 31 kJ, qL: 263 ± 26 kJ, P = 0.31) but was 5 ± 7% higher during DRY than during HUM (273 ± 29 kJ, 258 ± 28 kJ; P = 0.03). Compared to matched eumenorrhoeic athletes, chronic OCP use impaired the sweating onset threshold and thermosensitivity (both P < 0.01). In well-trained, OCP-using women exercising in the heat: (i) a performance-thermoregulatory trade-off occurred that required behavioural adjustment; (ii) humidity impaired performance as a result of reduced evaporative power despite matched WBGT; and (iii) the sudomotor but not behavioural thermoregulatory responses were impaired compared to matched eumenorrhoeic athletes.

Effects of ethinyl estradiol-containing oral contraception and other factors on body composition and muscle strength among young healthy females in Finland-A cross-sectional study.

OBJECTIVE: The aim of this cross-sectional study was to determine the association of hormonal contraception and other life-style factors and habits affecting body composition (BC) and muscle strength. STUDY DESIGN: We measured the body composition of 400 healthy Finnish women (aged 20-40 years) using total body dual energy x-ray absorptiometry (TB-DXA) as well as grip strength (GS [kPa]) with a hand-held dynamometer and knee extension strength (KES [kg]) between 2011 and 2014. Investigated body composition variables were appendicular skeletal mass (ASM [kg]), body mass index (BMI [kg/m2]), relative skeletal muscle index (RSMI [ASM/m2]), total lean mass (TLM [kg]), skeletal muscle index (SMI [TLM/weight × 100]) and fat-%. Participants filled out a questionnaire concerning life-style factors and habits: hormonal contraception, physical activity, alcohol consumption, age, pregnancies, smoking and self-assessed health that were also adjusting factors in the covariate model. We investigated the effects of hormonal contraception and other life-style factors and habits on body composition and muscle strength using AN(C)OVA in the analyses. RESULTS: Women using hormonal contraception with the combination of ethinyl estradiol + progestogen had significantly lower mean ASM (18.0), RSMI (6.5), TLM (40.8) (p < 0.01) and GS (34.6) (p < 0.001) compared to the women not using hormonal contraception with mean values of ASM (18.8), RSMI (6.7), TLM (42.6) and GS (36.9). After adjustment ASM (18.3), SMI (64.3), GS (35.2) (p < 0.05), RSMI (6.6) and TLM (41.2) (p < 0.01) were significantly lower and fat-% (31.4) higher (p < 0.05) compared to women not using hormonal contraception with mean values of ASM (19.0), SMI (66.1), GS (36.7), RSMI (6.8), TLM (42.7) and fat-% (29.8). CONCLUSION: Use of ethinyl estradiol + progestogen-containing hormonal contraception may have negative association with muscle mass and strength.

Síndrome de ovario poliquístico: casos confirmados y tratamiento en consulta externa del Hospital Escuela Universitario / Polycystic ovary syndrome: confirmed cases and treatment in the outpatient clinic of ̈Hospital Escuela Universitario

El síndrome de ovario poliquísticoes unaendocrinopatía frecuente en la mujer en edad fértil, causado por exceso de andrógenos y es causa de infertilidad anovulatoria. Actualmente uno de los criterios utilizados para el diagnóstico, son los de Rotterdam y para esto se necesita de la clínica (hiperandrogenismo y disfunción ovulatoria), exámenes de laboratorio (hiperandrogenismo) y/o ultrasonido característico de dicho síndrome. Objetivo:determinar el síndrome de ovario poliquístico confirmado por métodos laboratoriales e imágenes y tratamiento indicado en consulta externa del Hospital Escuela Universitario. Material y métodos: estudio retrospectivo, transversal, no aleatorio. Se revisaron 56 expedientes de pacientes con el diagnóstico de síndrome de ovario poliquístico valorados mediante criterios de Rotterdam, 31(55.4%) tenian diagnóstico ultrasonográfico. Se utilizó un instrumento de recolección de datos tipo cuestionario registrandose lo siguiente: edad, sintomatología, exámenes laboratoriales, diagnóstico con descripción ultrasonográficas y tratamiento farmacológico. Resultados: con el diagnóstico de síndrome ovario poliquístico, 31(55.4%) teníandiagnósticos1 Médico especialista en ginecología y obstetricia, Hospital Escuela Universitario2Estudiante de sexto año, Facultad de Ciencias Médicas, Universidad Nacional Autónoma de Honduras.Autor de correspondencia: Silder Moncada Correo electrónico: silderjavier78@gmail.comRecibido: 19/09/2017Aceptado: 07/02/2019ultrasonográficos, en 26(83.9%) pacientes no se encontró consignado en el expediente síntomas de hiperandrogenismo, se consignó acantosis nigricans en 2(6.5%), alopecia y acné 3(9.7%), respectivamente como signo hiperandrogénico. Los fármacos utilizados para tratar síndrome de ovario poliquístico fueron metformina y anticonceptivos orales. Conclusión: el diagnóstico y tratamiento de síndrome de ovario poliquístico no sigue protocolos estandarizados, ya que de los 31 expedientes con resultado por ultrasonido, solo 5(16.1%) reunían los criterios para el diagnóstico de dicha patología...(AU)