The impact of the first three months of the COVID-19 pandemic on the Australian trans community.

Background: Trans and gender diverse individuals (people who identify with a gender different to what was presumed for them at birth) are one of the most medically and socially marginalized groups in our community. The COVID-19 pandemic may compound preexisting depression and thoughts of self-harm or suicide. Aim: We aimed to explore the impact of the COVID-19 pandemic on the Australian trans community. Methods: An online cross-sectional survey was conducted between 1st May 2020 and 30th June 2020, amidst strict Australia-wide social restrictions. Australian trans people aged ≥16 years were eligible to participate. Survey questions explored the impact of the COVID-19 pandemic on living situation, employment, financial situation, and healthcare. Logistic regression to assess negative impacts due to COVID-19 on depression and thoughts of self-harm or suicide (measured by Patient Health Questionnaire-9 (PHQ-9) are presented as odds ratios (95% confidence interval)). Results: Of 1019 participants, 49.6% reported experiencing financial strain, 22% had reduced working hours, and 22.4% were unemployed (three times the national rate). Concerningly, 61.1% experienced clinically significant symptoms of depression (Patient Health Questionnaire-9 score ≥10), considerably higher than pre-COVID rates for the trans community and over twice the national rate. Moreover, 49% reported thoughts of self-harm or suicide (over three times the national rate) which was more likely if a person experienced cancelation or postponement of gender-affirming surgery (OR 1.56 (1.04, 2.35)), financial strain (OR 1.80 (1.36, 2.38)), or felt unsafe or afraid in their household (OR 1.96 (1.23, 3.08)). Discussion: Given rates of clinically significant depression and thoughts of self-harm or suicide are far higher in trans people than the general population, specific strategies to improve mental health in the trans community during the COVID-19 pandemic must be made a priority for policymakers, researchers, and health service providers to prevent suicide.Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1890659.

Haemolysis Detection in MicroRNA-Seq from Clinical Plasma Samples.

The abundance of cell-free microRNA (miRNA) has been measured in blood plasma and proposed as a source of novel, minimally invasive biomarkers for several diseases. Despite improvements in quantification methods, there is no consensus regarding how haemolysis affects plasma miRNA content. We propose a method for haemolysis detection in miRNA high-throughput sequencing (HTS) data from libraries prepared using human plasma. To establish a miRNA haemolysis signature we tested differential miRNA abundance between plasma samples with known haemolysis status. Using these miRNAs with statistically significant higher abundance in our haemolysed group, we further refined the set to reveal high-confidence haemolysis association. Given our specific context, i.e., women of reproductive age, we also tested for significant differences between pregnant and non-pregnant groups. We report a novel 20-miRNA signature used to identify the presence of haemolysis in silico in HTS miRNA-sequencing data. Further, we validated the signature set using firstly an all-male cohort (prostate cancer) and secondly a mixed male and female cohort (radiographic knee osteoarthritis). Conclusion: Given the potential for haemolysis contamination, we recommend that assays for haemolysis detection become standard pre-analytical practice and provide here a simple method for haemolysis detection.

Bone Microarchitecture in Transgender Adults: A Cross-Sectional Study.

Gender-affirming hormone therapy aligns physical characteristics with an individual's gender identity, but sex hormones regulate bone remodeling and influence bone morphology. We hypothesized that trans men receiving testosterone have compromised bone morphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti-androgen therapy, have preserved bone microarchitecture. We compared distal radial and tibial microarchitecture using high-resolution peripheral quantitative computed tomography images in a cross-sectional study of 41 trans men with 71 cis female controls, and 40 trans women with 51 cis male controls. Between-group differences were expressed as standardized deviations (SD) from the mean in age-matched cisgender controls with 98% confidence intervals adjusted for cross-sectional area (CSA) and multiple comparisons. Relative to cis women, trans men had 0.63 SD higher total volumetric bone mineral density (vBMD; both p = 0.01). Cortical vBMD and cortical porosity did not differ, but cortices were 1.11 SD thicker (p < 0.01). Trabeculae were 0.38 SD thicker (p = 0.05) but otherwise no different. Compared with cis men, trans women had 0.68 SD lower total vBMD (p = 0.01). Cortical vBMD was 0.70 SD lower (p < 0.01), cortical thickness was 0.51 SD lower (p = 0.04), and cortical porosity was 0.70 SD higher (p < 0.01). Trabecular bone volume (BV/TV) was 0.77 SD lower (p < 0.01), with 0.57 SD fewer (p < 0.01) and 0.30 SD thicker trabeculae (p = 0.02). There was 0.56 SD greater trabecular separation (p = 0.01). Findings at the distal radius were similar. Contrary to each hypothesis, bone microarchitecture was not compromised in trans men, perhaps because aromatization of administered testosterone prevented bone loss. Trans women had deteriorated bone microarchitecture either because of deficits in microstructure before treatment or because the estradiol dosage was insufficient to offset reduced aromatizable testosterone. Prospective studies are needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Short-Term Effects of Gender-Affirming Hormone Therapy on Dysphoria and Quality of Life in Transgender Individuals: A Prospective Controlled Study.

Background: Gender affirming hormone therapy (GAHT), whilst considered the standard of care in clinical guidelines for the treatment of many transgender (trans) people is supported by low quality evidence. In this prospective longitudinal controlled study, we aimed to examine the effect of newly commencing GAHT on gender dysphoria and quality of life (QoL) over a 6 month period. Methods: Adult trans (including those with binary and/or non-binary identities) people newly commencing standard full-doses of masculinising (n = 42; 35 = trans masculine, 7 = non-binary) or feminising (n = 35; 33 = trans feminine, 2 = non-binary) GAHT and cisgender participants (n=53 male, n=50 female) were recruited to participate in this longitudinal prospective study. This analysis of gender dysphoria measured by the Gender Preoccupation and Stability Questionnaire and QoL measured by the RAND Short-Form 36 Health survey at baseline, 3 and 6 months after commencement of GAHT was a prespecified secondary outcome. Dysphoria and QoL over time in those starting GAHT compared to cisgender comparison group matched for their presumed sex at birth is reported as the mean difference (95% confidence interval) adjusted for age. Results: In trans people initiating masculinising GAHT, there was a decrease in gender dysphoria with adjusted mean difference -6.80 (-8.68, -4.91), p < 0.001, and a clinically significant improvement in emotional well-being [adjusted mean difference 7.48 (1.32, 13.64), p = 0.018] and social functioning [adjusted mean difference 12.50 (2.84, 22.15), p = 0.011] aspects of QoL over the first 6 months of treatment relative to the cisgender female comparison group. No significant differences were observed in other QoL domains. In trans people initiating feminising GAHT, there was a decrease in gender dysphoria [adjusted mean difference -4.22 (-6.21, -2.24), p < 0.001] but no differences in any aspects of QoL were observed. Conclusions: In the short-term, our findings support the benefit of initiating masculinising or feminising GAHT for gender dysphoria. Masculinising GAHT improves emotional well-being and social functioning within 6 months of treatment. Multidisciplinary input with speech pathology and surgery to support trans people seeking feminisation is likely needed. Further longitudinal studies controlled for other confounders (such as the presence of social supports) contributing to QoL are needed.

Blood Pressure Effects of Gender-Affirming Hormone Therapy in Transgender and Gender-Diverse Adults.

[Figure: see text].

Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function.

Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6-13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

Global Coagulation Assays in Transgender Women on Oral and Transdermal Estradiol Therapy.

CONTEXT: The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests. OBJECTIVE: To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women. DESIGN: Cross-sectional case-control study. SETTING: General community. PARTICIPANTS: Transgender women, cisgender male and cisgender female controls. MAIN OUTCOME MEASURES: Citrated blood samples were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram); and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented. RESULTS: Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum amplitude + 6.94 mm (3.55, 10.33); P < 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91); P = 0.009; peak thrombin + 38.10 nM (2.27, 73.94); P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25); P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters. CONCLUSION: Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters.

Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes: A prospective cohort of nulliparous women.

BACKGROUND: Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated. METHODS AND FINDINGS: Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks' gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ≥80 cm, along with any 2 of the following: raised trigycerides (≥1.70 mmol/l [≥150 mg/dl]), reduced high-density lipoprotein cholesterol (<1.29 mmol/l [<50 mg/dl]), raised blood pressure (BP) (i.e., systolic BP ≥130 mm Hg or diastolic BP ≥85 mm Hg), or raised plasma glucose (≥5.6 mmol/l). Log-binomial regression analyses were used to examine the risk for each pregnancy outcome (GDM, PE, large for gestational age [LGA], small for gestational age [SGA], and spontaneous preterm birth [sPTB]) with each of the 5 individual components for MetS and as a composite measure (i.e., MetS, as defined by the IDF). The relative risks, adjusted for maternal BMI, age, study centre, ethnicity, socioeconomic index, physical activity, smoking status, depression status, and fetal sex, are reported. A total of 5,530 women were included, and 12.3% (n = 684) had MetS. Women with MetS were at an increased risk for PE by a factor of 1.63 (95% CI 1.23 to 2.15) and for GDM by 3.71 (95% CI 2.42 to 5.67). In absolute terms, for PE, women with MetS had an adjusted excess risk of 2.52% (95% CI 1.51% to 4.11%) and, for GDM, had an adjusted excess risk of 8.66% (95% CI 5.38% to 13.94%). Diagnosis of MetS was not associated with increased risk for LGA, SGA, or sPTB. Increasing BMI in combination with MetS increased the estimated probability for GDM and decreased the probability of an uncomplicated pregnancy. Limitations of this study are that there are several different definitions for MetS in the adult population, and as there are none for pregnancy, we cannot be sure that the IDF criteria are the most appropriate definition for pregnancy. Furthermore, MetS was assessed in the first trimester and may not reflect pre-pregnancy metabolic health status. CONCLUSIONS: We did not compare the impact of individual metabolic components with that of MetS as a composite, and therefore cannot conclude that MetS is better at identifying women at risk. However, more than half of the women who had MetS in early pregnancy developed a pregnancy complication compared with just over a third of women who did not have MetS. Furthermore, while increasing BMI increases the probability of GDM, the addition of MetS exacerbates this probability. Further studies are required to determine if individual MetS components act synergistically or independently.

Pre-pregnancy fast food and fruit intake is associated with time to pregnancy.

STUDY QUESTION: Is preconception dietary intake associated with reduced fecundity as measured by a longer time to pregnancy (TTP)? SUMMARY ANSWER: Lower intake of fruit and higher intake of fast food in the preconception period were both associated with a longer TTP. WHAT IS KNOWN ALREADY: Several lifestyle factors, such as smoking and obesity, have consistently been associated with a longer TTP or infertility, but the role of preconception diet in women remains poorly studied. Healthier foods or dietary patterns have been associated with improved fertility, however, these studies focused on women already diagnosed with or receiving treatments for infertility, rather than in the general population. STUDY DESIGN, SIZE, DURATION: This was a multi-center pregnancy-based cohort study of 5628 nulliparous women with low-risk singleton pregnancies who participated in the Screening for Pregnancy Endpoints (SCOPE) study. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 5598 women were included. Data on retrospectively reported TTP and preconception dietary intake were collected during the first antenatal study visit (14-16 weeks' gestation). Dietary information for the 1 month prior to conception was obtained from food frequency questions for fruit, green leafy vegetables, fish and fast foods, by a research midwife. Use of any fertility treatments associated with the current pregnancy was documented (yes, n = 340, no, n = 5258). Accelerated failure time models with log normal distribution were conducted to estimate time ratios (TR) and 95% CIs. The impact of differences in dietary intake on infertility (TTP >12 months) was compared using a generalized linear model (Poisson distribution) with robust variance estimates, with resulting relative risks (RR) and 95% CIs. All analyses were controlled for a range of maternal and paternal confounders. Sensitivity analyses were conducted to explore potential biases common to TTP studies. MAIN RESULTS AND THE ROLE OF CHANCE: Lower intakes of fruit and higher intakes of fast food were both associated with modest increases in TTP and infertility. Absolute differences between the lowest and highest categories of intake for fruit and fast food were in the order of 0.6-0.9 months for TTP and 4-8% for infertility. Compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day (TR = 1.06, 95% CI: 0.97-1.15), 1-6 times/week (TR = 1.11, 95% CI: 1.01-1.22) or <1-3 times/month (TR = 1.19, 95% CI: 1.03-1.36), corresponded to 6, 11 and 19% increases in the median TTP (Ptrend = 0.007). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2-<4 times/week (TR = 0.89, 95% CI: 0.81-0.98), >0-<2 times/week (TR 0.79, 95% CI 0.69-0.89) or no fast food (TR = 0.76, 95% CI: 0.61-0.95), corresponded to an 11, 21 and 24% reduction in the median TTP (Ptrend <0.001). For infertility, compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day, 1-6 times/week or <1-3 times/month corresponded to a 7, 18 and 29% increase in risk of infertility (Ptrend = 0.043). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2-<4 times/week, >0-<2 times/week, or no fast food, corresponded to an 18, 34 and 41% reduced risk of infertility (Ptrend <0.001). Pre-pregnancy intake of green leafy vegetables or fish were not associated with TTP or infertility. Estimates remained stable across a range of sensitivity analyses. LIMITATIONS, REASONS FOR CAUTION: Collection of dietary data relied on retrospective recall and evaluated a limited range of foods. Paternal dietary data was not collected and the potential for residual confounding cannot be eliminated. Compared to prospective TTP studies, retrospective TTP studies are prone to a number of potential sources of bias. WIDER IMPLICATIONS OF THE FINDINGS: These findings underscore the importance of considering preconception diet for fecundity outcomes and preconception guidance. Further research is needed assessing a broader range of foods and food groups in the preconception period. STUDY FUNDING/COMPETING INTEREST(S): The SCOPE database is provided and maintained by MedSciNet AB (http://medscinet.com). The Australian SCOPE study was funded by the Premier's Science and Research Fund, South Australian Government (http://www.dfeest.sa.gov.au/science-research/premiers-research-and-industry-fund). The New Zealand SCOPE study was funded by the New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council (04/198); Evelyn Bond Fund, Auckland District Health Board Charitable Trust. The Irish SCOPE study was funded by the Health Research Board of Ireland (CSA/2007/2; http://www.hrb.ie). The UK SCOPE study was funded by National Health Service NEAT Grant (Neat Grant FSD025), Biotechnology and Biological Sciences Research council (www.bbsrc.ac.uk/funding; GT084) and University of Manchester Proof of Concept Funding (University of Manchester); Guy's and St. Thomas' Charity (King's College London) and Tommy's charity (http://www.tommys.org/; King's College London and University of Manchester); and Cerebra UK (www.cerebra.org.uk; University of Leeds). L.E.G. is supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (ID 1070421). L.J.M. is supported by a SACVRDP Fellowship; a program collaboratively funded by the National Heart Foundation, the South Australian Department of Health and the South Australian Health and Medical Research Institute. L.C.K. is supported by a Science Foundation Ireland Program Grant for INFANT (12/RC/2272). C.T.R. was supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (GNT1020749). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications.

Widespread legalisation of marijuana raises safety concerns for its use in pregnancy. This study investigated the association of marijuana use prior to and during pregnancy with pregnancy outcomes in a prospective cohort of 5588 nulliparous women from the international SCOPE study. Women were assessed at 15±1 and 20±1 weeks' gestation. Cases [278 Preeclampsia, 470 gestational hypertension, 633 small-for-gestational-age, 236 spontaneous preterm births (SPTB), 143 gestational diabetes] were compared separately with 4114 non-cases. Although the numbers are small, continued maternal marijuana use at 20 weeks' gestation was associated with SPTB independent of cigarette smoking status [adj OR 2.28 (95% CI:1.45-3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41-3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks' gestation had a greater effect size [adj OR 5.44 (95% CI 2.44-12.11)]. Our data indicate that increasing use of marijuana among young women of reproductive age is a major public health concern.