Pharmacotherapeutic potential of ginkgetin against polystyrene microplastics-instigated testicular toxicity in rats: A biochemical, spermatological, and histopathological assessment.

Polystyrene microplastics (PSMPs) have emerged as a ubiquitous environmental toxicant that affects different organs including testes. Ginkgetin (GNG) is a biflavonoid that shows antioxidant properties. The current research was undertaken to evaluate the ameliorative potential of GNG against PSMPs-instigated testicular damages. Forty-eight albino rats (male) were randomly divided into 4 equal groups: control, PSMPs-treated group (0.01 mgkg-1), GNG + PSMPs-exposed group (25 mgkg-1 + 0.01 mgkg-1), and only GNG-supplemented group (25 mgkg-1). After 56 days of treatment, it was revealed that PSMPs significantly reduced the activity of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GSR), while concurrently augmented the levels of lipid peroxidation marker, i.e., malondialdehyde (MDA) along with reactive oxygen species (ROS). Rats administered with PSMPs showed a significant reduction in the spermatogenic indices (sperm count, viability, and motility), HOS coiled tail sperm along with increased sperm structural deformities, i.e., tail, head, and mid-piece. Additionally, PSMPs exposure decreased the levels of testosterone, luteinizing (LH), and follicle-stimulating hormones (FSH). Besides, administration of PSMPs reduced the steroidogenic enzymes (13ß-HSD, StAR, and 17ß-HSD) and Bcl-2 expression, while augmented the caspase-3 and Bax expression. PSMPs also elevated the levels of inflammatory markers (IL-6, IL-1ß, TNF-α, and NF-κB) and activity of COX-2 in the testes. Furthermore, PSMPs treatment induced various histopathological damages in the testes of rats. Therefore, findings of the current study suggested that GNG effectively mitigated the PSMPs-induced testicular toxicity owing to its chemoprotective potential possibly through its anti-inflammatory, antioxidant, anti-apoptotic, and androgenic properties.

Assessment of Epiregulin Effect and its Combination with Gonadotropins on Proliferation, Apoptosis, and Secretory Activity by Human Ovarian Cells.

The release of epidermal growth factor ligand epiregulin (EREG) by human ovarian granulosa cells, its direct action on basic ovarian cell functions, and interrelationships with gonadotropins were investigated. We examined (1) the ovarian production of EREG (the time-dependent accumulation of EREG in the medium incubated with human ovarian granulosa cells, and (2) the effect of the addition of EREG (0, 1, 10, and 100 ng.ml-1) given alone or in combination with FSH or LH (100 ng.ml-1) on basic granulosa cells functions. Viability, proliferation (accumulation of PCNA and cyclin B1) and apoptosis (accumulation of bax and caspase 3), the release of steroid hormones (progesterone, testosterone, and estradiol), and prostaglandin E2 (PGE2) were analyzed by using the Trypan blue exclusion test, quantitative immunocytochemistry, and ELISA. A significant time-dependent accumulation of EREG in a medium cultured with human granulosa cells with a peak at 3 and 4 days was observed. The addition of EREG alone increased cell viability, proliferation, progesterone, testosterone, and estradiol release, decreased apoptosis, bud did not affect PGE2 release. The addition of either FSH or LH alone increased cell viability, proliferation, progesterone, testosterone, estradiol, and PGE2 release and decreased apoptosis. Furthermore, both FSH and LH mostly promoted the stimulatory action of EREG on granulosa cell functions. These results demonstrated, that EREG produced by ovarian cells can be an autocrine/paracrine stimulator of human ovarian cell functions. Furthermore, they demonstrate the functional interrelationship between EREG and gonadotropins in the control of ovarian functions.

The cost of the circadian desynchrony on the Leydig cell function.

The increased frequency of different lifestyles that disrupts circadian rhythms, together with a trend in the accretion of male idiopathic infertility, imposes the necessity to understand the contribution of circadian rhythms disruption to fertility regulation. In this study, the effects of circadian desynchrony (CD) on the steroidogenic capacity of adult Leydig cells were studied. Adult rats were housed under a disturbing light regime (2 days of constant light, 2 days of continual dark, and 3 days of 12:12 h light:dark schedule) designed to mimic shiftwork in humans. CD was characterized by changed and decreased rhythmic locomotor activity and reduced blood testosterone. In the Leydig cells changed transcription of the clock genes (Bmal1, Clock, Cry1 and Reverba/b increased while Per1/2 reversed phase) was detected. This was followed by reduced transcription of genes (Star, Cyp11a1, and Hsd3b1/2) primarily involved in mitosteroidogenesis. In parallel, mitochondrial membrane potential (Δψi) and ATP production declined losing their characteristic oscillatory pattern. Also, the main markers of mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Cytc), fusion (Mfn2), and mitophagy (Pink1 and Tfeb) were disturbed. Collectively, CD targets mitochondria in Leydig cells by reducing mitosteroidogenesis, mitoenergetics, and disturbing mitochondrial dynamics. These changes contribute to testosterone decline compromising androgen-dependent functions, including reproduction.

Steroid hormones in hair and fresh wounds reveal sex specific costs of reproductive engagement and reproductive success in wild house mice (Mus musculus domesticus).

Not only males but also females compete over reproduction. In a population of free-living house mice (Mus musculus domesticus), we analyzed how (metabolic) costs of aggressive interactions (reflected in fresh wounds and long-term corticosterone concentrations in hair) are predicted by individual reproductive physiology and reproductive success in males and females. Over eight years, we studied wounds and reproduction of more than 2800 adults under naturally varying environmental conditions and analyzed steroid hormones from more than 1000 hair samples. Hair corticosterone were higher and wounds more frequent in males than females. In males, wound occurrence increased with increasing breeding activity in the population, without affecting hair corticosterone levels. Unexpectedly, individual male reproductive success did not predict wounds, while hair corticosterone increased with increasing levels of hair testosterone and reproductive success. High corticosterone in hair of males might therefore reflect metabolic costs of fighting over reproduction. In females, hair corticosterone was generally lower than in males and high levels did not impede pregnancy. Reproductive investment (reflected in hair progesterone) was dissociated from reproductive success. Occasional wounds in females indicated individuals without recent reproductive success and revealed reproductive competition, presumably driven by instability in the social environment. In both sexes, corticosterone increased with age, but there was no evidence that received overt aggression, as indicated by wounds or elevated corticosterone, suppressed reproductive physiology. Our results diverge from laboratory findings and emphasize the need to also study animals in their natural environment in order to understand the complexity of their behavioral physiology.

Potential Assessment of UGT2B17 Inhibition by Salicylic Acid in Human Supersomes In Vitro.

Glucuronidation is a Phase 2 metabolic pathway responsible for the metabolism and excretion of testosterone to a conjugate testosterone glucuronide. Bioavailability and the rate of anabolic steroid testosterone metabolism can be affected upon UGT glucuronidation enzyme alteration. However, there is a lack of information about the in vitro potential assessment of UGT2B17 inhibition by salicylic acid. The purpose of this study is to investigate if UGT2B17 enzyme activity is inhibited by salicylic acid. A UGT2B17 assay was developed and validated by HPLC using a C18 reversed phase column (SUPELCO 25 cm × 4.6 mm, 5 µm) at 246 nm using a gradient elution mobile phase system: (A) phosphate buffer (0.01 M) at pH = 3.8, (B) HPLC grade acetonitrile and (C) HPLC grade methanol. The UGT2B17 metabolite (testosterone glucuronide) was quantified using human UGT2B17 supersomes by a validated HPLC method. The type of inhibition was determined by Lineweaver-Burk plots. These were constructed from the in vitro inhibition of salicylic acid at different concentration levels. The UGT2B17 assay showed good linearity (R2 > 0.99), acceptable recovery and accuracy (80-120%), good reproducibility and acceptable inter and intra-assay precision (<15%), low detection (6.42 and 2.76 µM) and quantitation limit values (19.46 and 8.38 µM) for testosterone and testosterone glucuronide respectively, according to ICH guidelines. Testosterone and testosterone glucuronide were found to be stable up to 72 h in normal laboratory conditions. Our investigational study showed that salicylic acid uncompetitively inhibited UGT2B17 enzyme activity. Thus, drugs that are substrates for the UGT2B17 enzyme have negligible potential effect of causing interaction with salicylic acid in humans.

The construction of categories in sport: Unfair advantages, equality of opportunity and strict attainability.

On 8 September 2020, the Swiss Federal Supreme Sport dismissed the double appeal by Caster Semenya against the decision of the Court for Arbitration of Sport to uphold the World Athletics regulations restricting testosterone levels in female runners. On 24 February 2021, Semenya appealed to the European Court of Human Rights. This is the most recent episode of an international legal case which was ignited at the 2009 Berlin World Track Championship, when Semenya was 18 years old. Semenya's case has generated an intricate web of questions for classification in sport that are yet to be resolved. In this paper we aim to disentangle them. We proceed as follows: we describe the problem of binary classification related to Semenya's case and introduce the concept of property advantage, and the fair equality of opportunity principle. We compare Semenya's case with Eero Mantyranta's case and fail to identify a way according to which the two cases could justifiably be treated differently. We then discuss three possible ways to organize sport categories based on the combination of Loland's fair equality of opportunity principle and our strict attainability criterion, and outline the implications of each alternative for international sports law regulation. Finally, we summarize and outline the legacy of Semenya for the construction of categories in sport.

Assessment of reproductive toxicity and genotoxicity of Aconiti Lateralis Radix Praeparata and its processed products in male mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconiti Lateralis Radix Praeparata (Chinese name: Fuzi), the root of Aconitum carmichaelii Debx., is a representative medicine for restoring yang and rescuing patient from collapse. However, less studies had been reported on the reproductive toxicity and genotoxicity of Fuzi. According to the principle of reducing toxicity and preserving efficiency, only processed products of Fuzi are commonly applied in clinic, including Baifupian, Heishunpian and Danfupian. However, whether processing could alleviate the reproductive toxicity and genotoxicity of Fuzi had not been revealed. AIM OF THE STUDY: To assess the effect and possible mechanism of Fuzi and its processed products on reproductive toxicity and genotoxicity in male mice. MATERIALS AND METHODS: Aqueous extracts of Fuzi and its processed products (Baifupian, Heishunpian and Danfupian, 5.85 g/kg) were administrated by gavage once daily for fourteen consecutive days. The reproductive toxicity was evaluated by testis weight, testis ratio, testis histopathology, sperm count, sperm viability rate and sperm deformity rate. The genotoxicity was evaluated by comet assay and micronucleus test in sperm, peripheral blood cell and bone marrow cell. Possible mechanisms of attenuating toxicity by processing were analyzed by detecting the level of testosterone, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and catalase (CAT). RESULTS: Fuzi significantly caused different degrees of reproductive toxicity and genotoxicity, specifically reducing the weight and testicular coefficient of testis, causing obvious pathological changes in testicular tissue, reducing sperm count and sperm viability rate, increasing sperm deformity rate and DNA damage in sperm/peripheral blood cells/bone marrow cells. Moreover, Fuzi decreased the level of testosterone, SOD, GSH and CAT, while increased the level of MDA in serum. Notably, the reproductive toxicity and genotoxicity induced by the processed products, especially Heishunpian and Danfupian, were significantly lowered compared to Fuzi. Processing could increase the level of testosterone, SOD, GSH, CAT and decrease the level of MDA compared to Fuzi. CONCLUSION: Fuzi and its processed products had reproductive toxicity and genotoxicity, but the toxicity of processed products was significantly weakened compared to Fuzi. The protective mechanism of processing to reduce the toxicity of Fuzi might be related to increasing the level of testosterone and decreasing oxidative stress.

Why does COVID-19 kill more elderly men than women? Is there a role for testosterone?

BACKGROUND: Recent epidemiological data indicate that there may be a gender predisposition to COVID-19, with men predisposed to being most severely affected, and older men accounting for most deaths. OBJECTIVES: Provide a review of the research literature, propose hypotheses, and therapies based on the potential link between testosterone (T) and COVID-19 induced mortality in elderly men. MATERIALS AND METHODS: A search of publications in academic electronic databases, and government and public health organization web sites on T, aging, inflammation, severe acute respiratory syndrome (SARS) due to coronavirus (CoV) 2 (SARS-CoV-2) infection, and COVID-19 disease state and outcomes was performed. RESULTS: The link between T, the immune system, and male aging is well-established, as is the progressive decline in T levels with aging. In women, T levels drop before menopause and variably increase with advanced age. Elevated IL-6 is a characteristic biomarker of patients infected with COVID-19 and has been linked to the development of the acute respiratory distress syndrome (ARDS). Thus far, half of the admitted COVID-19 patients developed ARDS, half of these patients died, and elderly male patients have been more likely to develop ARDS and die. Low T is associated with ARDS. These data suggest that low T levels may exacerbate the severity of COVID-19 infection in elderly men. It may also stand to reason that normal T levels may offer some protection against COVID-19. SARS-CoV-2 binds to the angiotensin-converting enzyme 2, present in high levels in the testis. CONCLUSION: At present, it is not known whether low T levels in aging hypogonadal males create a permissive environment for severe responses to COVID-19 infection or if the virus inhibits androgen formation. Given the preponderance of COVID-19 related mortality in elderly males, additional testing for gonadal function and treatment with T may be merited.

SARS-CoV-2, testosterone and frailty in males (PROTEGGIMI): A multidimensional research project.

Preliminary published data depict a much greater prevalence of males with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) referred for intensive care unit admission and severe sequelae in several countries. In this context, males seem to not only be more susceptible to the infection compared to female subjects, at least in Western countries, but their case fatality rate attributable to SARS-CoV-2 infection is also highest. Therefore, we may speculate that the different hormonal milieu could have a more profound pathophysiological role in association with SARS-CoV-2, with endogenous testosterone leaving men more prone to develop more serious complications related to the SARS-CoV-2 infection. Another option is that SARS-CoV-2 infection per se causes an acute stage of male hypogonadism, the depletion of androgenic action triggering serious or an even fatal course of the disease. Therefore, we strongly advocate the development of a prospective multidimensional andrological translational research project in men, which we called the PROTEGGIMI study. In this Opinion Article, we will not only highlight novel research activity in this area but also invite other researchers and learned scientific societies to join us in our efforts to understand an important and very newly discovered gap in knowledge, which may have serious implications for the lives of millions of men.

Gradual and Discrete Ontogenetic Shifts in Rattlesnake Venom Composition and Assessment of Hormonal and Ecological Correlates.

Ontogenetic shifts in venom occur in many snakes but establishing their nature as gradual or discrete processes required additional study. We profiled shifts in venom expression from the neonate to adult sizes of two rattlesnake species, the eastern diamondback and the timber rattlesnake. We used serial sampling and venom chromatographic profiling to test if ontogenetic change occurs gradually or discretely. We found evidence for gradual shifts in overall venom composition in six of eight snakes, which sometimes spanned more than two years. Most chromatographic peaks shift gradually, but one quarter shift in a discrete fashion. Analysis of published diet data showed gradual shifts in overall diet composition across the range of body sizes attained by our eight study animals, while the shifts in abundance of different prey classes varied in form from gradual to discrete. Testosterone concentrations were correlated with the change in venom protein composition, but the relationship is not strong enough to suggest causation. Venom research employing simple juvenile versus adult size thresholds may be failing to account for continuous variation in venom composition lifespan. Our results imply that venom shifts represent adaptive matches to dietary shifts and highlight venom for studies of alternative gene regulatory mechanisms.

In vitro assessment of the impact of nickel on the viability and steroidogenesis in the human adrenocortical carcinoma (NCI-H295R) cell line.

Nickel is a ubiquitous environmental pollutant, which has various effects on reproductive endocrinology. In this study, human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biological model to study the effect of nickel chloride (NiCl2) on the viability and steroidogenesis. The cells were exposed to different concentrations (3.90; 7.80; 15.60; 31.20; 62.50; 125; 250 and 500 microM) of NiCl2 and compared with control group (culture medium without NiCl2). The cell viability was measured by the metabolic activity assay. Production of sexual steroid hormones was quantified by enzyme linked immunosorbent assay. Following 48 h culture of the cells in the presence of NiCl2 a dose-dependent depletion of progesterone release was observed even at the lower concentrations. In fact, lower levels of progesterone were detected in groups with higher doses (>/=125 microM) of NiCl2 (P<0.01), which also elicited cytotoxic action. A more prominent decrease in testosterone production (P<0.01) was also noted in comparison to that of progesterone. On the other hand, the release of 17beta-estradiol was substantially increased at low concentrations (3.90 to 62.50 microM) of NiCl2. The cell viability remained relatively unaltered up to 125 microM (P>0.05) and slightly decreased from 250 microM of NiCl2 (P<0.05). Our results indicate endocrine disruptive effect of NiCl2 on the release of progesterone and testosterone in the NCI-H295R cell line. Although no detrimental effect of NiCl2 (

Life history and individual differences in male testosterone: Mixed evidence for early environmental calibration of testosterone response to first-time fatherhood.

Male testosterone (T) decreases in response to childbirth. Longitudinal support for this has come from samples across cultures. In this study, we look at individual differences in this phenomenon. Utilizing a sample of U.S. fathers, we employ life history theory to investigate the influence of a father's early experience on his neuroendocrine response to fatherhood. We conducted three home visits (n = 226 fathers) from the third trimester of pregnancy to when infants were 10 months old. In this sample, T declined from the third trimester of (a partner's) pregnancy to the early months of the postnatal period. T recovered to pre-birth levels by the time infants reached 10 months old. We did not find any evidence that one's subjective experience of their early environment could account for any meaningful variability in T calibration. Objective, "event" measures of early harshness (i.e., death of a sibling/friend) and unpredictability (i.e., parent upheaval) each uniquely predicted a younger age of sexual debut. Neither harshness nor unpredictability had any (direct or indirect) effects on T calibration. Age of sexual debut did predict the rate of T recovery from 3 to 10 months postnatal. The younger one's sexual debut, the more accelerated their T ascent during this period. We discuss the potential reasons for, and implications of our mixed results.

Vascular Pathways of Testosterone: Clinical Implications.

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Testosterone (T) is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men. At the vascular level, the key effect of T is the vasorelaxation. This review discusses the molecular pathways and clinical implications of T in the vascular system. Firstly, the mechanisms involved in the T vasodilator effect will be presented. Then, it will be discussed the association of T with the main risks for CVD, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia and hypertension. Several studies have shown a correlation between low T levels and an increased prevalence of several CVD. These observations suggest that T has beneficial effects on the cardiovascular system and that testosterone replacement therapy may become a therapeutic reality for some of these disorders. Graphical abstract .

Assessment of reproductive disorder (imposex) induced by tributyltins in marine gastropods.

Imposex is a genital disorder characterized by imposition of male sexual characteristics in female gastropods due to exposure to tributyltin (TBT). TBT is used as biocidal agent in antifouling paints, applied on the ship hulls and marine submerged structures such as fishing gears and buoys. In the present study bioassay experiment was carried out to determine imposex inductive and endocrine disruptive effect of TBT in two species of gastropods of genus Thais. In this experiment normal specimens of T. bufo and T. rudolphi were exposed to three different concentrations (100, 500 and 1000ngl-1) of TBTCl for four weeks in laboratory and at the end of experiment level of free testosterone and TBT body burden was estimated by radioimmunoassay and gas chromatograph coupled with a flame photometric detector respectively. In both tested species exposed to 500 and 1000ngl-1 of TBT imposex stages developed, while in 100ng l-1 and control groups showed no imposex condition. Elevation of free testosterone level in imposex females has also been observed. These observations indicate that the TBT act as potential imposex inducer and endocrine disruptor in the targeted gastropod species and these species can be used as sensitive biomonitoring tool for TBT contamination.

Physiological and economic benefits of abandoning invasive surgical procedures and enhancing animal welfare in swine production.

Food-animal welfare is a major ethical and social concern. Pork is the most consumed meat worldwide, with over a billion pigs slaughtered annually. Most of these pigs routinely undergo painful surgical procedures (surgical castration, tail docking, teeth clipping), which farmers often reluctant to avoid, claiming it would increase cost and reduce production efficiency. Herein, this study indicates that these procedures compromise pigs' health and condition. Replacing surgical castration with immunocastration, avoiding tail docking and teeth clipping, and providing environmental enrichment, resulted in significant increase in weight gain, lowered risks for injuries and death, and reduced saliva and hair cortisol, both biomarkers for stress. Testosterone and DHEA analyses confirmed that immunocastration was an effective alternative to surgical castration. Economic models for the entire US swine market revealed that following across-the-board acceptance of this management, pork meat price is expected to drop, while the total annual social welfare (combined consumer and producer surplus) is expected to increase by $US 1.48 to 1.92 billion. In conclusion, sustainable swine farming management can be beneficial for both animals and farmers. Applying such welfare-friendly management is expected to reduce stress, enhance piglet/pig welfare and production, and improve the economics of swine operations in the global agro-food system.

Providing Patient-Centered Perinatal Care for Transgender Men and Gender-Diverse Individuals: A Collaborative Multidisciplinary Team Approach.

BACKGROUND: Little is documented about the experiences of pregnancy for transgender and gender-diverse individuals. There is scant clinical guidance for providing prepregnancy, prenatal, intrapartum, and postpartum care to transgender and gender-diverse people who desire pregnancy. CASE: Our team provided perinatal care to a 20-year-old transgender man, which prompted collaborative advocacy for health care systems change to create gender-affirming patient experiences in the perinatal health care setting. CONCLUSION: Systems-level and interpersonal-level interventions were adopted to create gender-affirming and inclusive care in and around pregnancy. Basic practices to mitigate stigma and promote gender-affirming care include staff trainings and query and use of appropriate name and pronouns in patient interactions and medical documentation. Various factors are important to consider regarding testosterone therapy for transgender individuals desiring pregnancy.

Assessment of the effective impact of bisphenols on mitochondrial activity and steroidogenesis in a dose-dependency in mice TM3 Leydig cells.

The increasing worldwide production of bisphenols has been associated to several human diseases, such as chronic respiratory and kidney diseases, diabetes, breast cancer, prostate cancer, behavioral troubles and reproductive disorders in both sexes. The aim of the present in vitro study was to evaluate the potential impact bisphenols A, B, S and F on the cell viability and testosterone release in TM3 Leydig cell line. Mice Leydig cells were cultured in the presence of different concentrations of bisphenols (0.04-50 µg.ml-1) during 24 h exposure. Quantification of the cell viability was assessed using the metabolic activity assay, while the level of testosterone in cell culture media was determined by enzyme-linked immunosorbent assay. Within the panel of substances under investigations, the higher experimental concentrations (10; 25 and 50 µg.ml-1) significantly (P<0.001) decreased Leydig cells viability, while the same doses of BPA and BPB also reduced testosterone production significantly (P<0.001). Taken together, the results of our study reported herein is a consistent whit the conclusion that higher experimental doses of bisphenols have a cytotoxic effect and could have a dose-dependent impact on testosterone production.

Assessment of free testosterone concentration.

Testosterone (T) is strongly bound to sex hormone binding globulin and measurement of free T may be more appropriate than measuring total serum T, according to the free hormone theory. This view remains controversial and it has its detractors who claim that little extra benefit is gained than simply measuring total T, but it is endorsed by recent clinical practice guidelines for investigation of androgen disorders in both men and women. Free T measurement is very challenging. The gold standard equilibrium dialysis methods are too complex for use in routine clinical laboratories, assays are not harmonized and consequently there are no common reference intervals to aid result interpretation. The algorithms derived for calculating free T are inaccurate because they were founded on faulty models of testosterone binding to SHBG, however they can still give clinically useful results. To negate the effects of differences in binding protein constants, some equations for free T have been derived from accurate measurement of testosterone in large population studies, however a criticism is that the equations may not hold true in different patient populations. The free androgen index is not recommended for use in men because of inaccuracy at extremes of SHBG concentration, and in women it can also give inaccurate results when SHBG concentrations are low. If the free hormone hypothesis is to be believed, then calculated free testosterone may offer the best way forward but better equations are needed to improve accuracy and these should be derived from detailed knowledge of testosterone binding to SHBG. There is still much work to be done to improve harmonization of T and SHBG assays between laboratories because these can have a profound effect on the equations used to calculate free testosterone.

Within- and between-person variation in morning testosterone is associated with economic risk-related decisions in athletic women across the menstrual cycle.

Literature suggests that women experience ovulatory shifts in risk-taking behaviours across different domains, which might be partly attributed to changes in testosterone (T). Thus, we investigated associations between menstrual variability in T concentrations and economic risk-related decisions among athletic women. Thirty-five women were monitored across three consecutive menstrual cycles. Testing occurred on day seven (D7), 14 (D14) and 21 (D21) following the onset of menses. The morning (7 to 8 am) assessment of salivary T (sal-T) and cortisol (sal-C) was followed by the economic Hawk-Dove game (11 am to 12 pm) played in pairs, where hawk decisions were used to index risk. Morning sal-T concentration increased from D7 to D14, before decreasing on D21 (p < 0.001), representing moderate effect size (ES) changes of 0.6 to 0.8. Morning sal-C did not vary over time. Hawk choices paralleled the sal-T results, being elevated on D14 (p < 0.001) with large ES changes of 1.8. Regression analyses revealed that morning sal-T concentration was positively related (p ≤ 0.01) to the number of hawks chosen between- (beta = 0.47) and within-participants (beta = 0.10) when controlling for training hours and menstrual day. In summary, the risk-related choices of athletic women during a dyadic contest covaried with morning sal-T concentrations across the menstrual cycle. Both outcomes were positively correlated on a within- and between-person level. Confirming the major sources of T variation across the menstrual cycle, whilst discerning its relationship with other risk-related behaviours, would be worthwhile avenues for research.

Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers.

BACKGROUND: Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality. METHODS: In this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups. RESULTS: FF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4-438) vs 64.4 (43.8-152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5-466.7) vs 354 (179-511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa. CONCLUSIONS: Let-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients. TRIAL REGISTRATION: Clinicaltrials.gov - NCT02661932 , registered 25 January 2016, retrospectively registered.