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 wellbeing 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.Lucas Foster Skewis, Ingrid Bretherton, Shalem Y. Leemaqz, Jeffrey D. Zajac, and Ada S. Cheun

Effects of low-dose oral micronised progesterone on sleep, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy: a prospective controlled study

Objective: The role of micronised progesterone in hormone regimens for transgender individuals undergoing feminising hormone therapy remains uncertain. We aimed to determine the effect of oral micronised progesterone on sleep quality, psychological distress, and breast development in transgender individuals undergoing feminising hormone therapy. Design: Prospective case–control study. Twenty-three transgender individuals on stable oestradiol treatment newly commencing 100 mg oral progesterone (n = 23) and controls continuing standard care (n = 19) were assessed over 3 months. Methods: Pittsburgh Sleep Quality Index (PSQI), Kessler psychological distress scale (K10), and Tanner stage to assess breast development were assessed at 0 and 3 months. Nonparametric analysis of covariance was used to compare difference s between groups. Results: Compared with controls over 3 months, there was no difference i n PSQI (P = 0.35), K10 (P = 0.64), or Tanner stage (P = 0.42). There was no significant difference in the proportion of individuals with clinically significant improvement in PSQI (25% vs 22%, P = 0.84). One individual had a significant deterioration in psychological distress that improved following the cessation of progesterone. Conclusions: Low-dose progesterone was not associated with changes in sleep quality, psychological distress, or breast development over 3 months follow-up, though there was significant inter-individual variability. Larger, placebo-controlled trials are required to further evaluate different doses of progesterone in feminising hormone therapy regimens.Brendan J Nolan, Aviva S Frydman, Shalem Y Leemaqz, Meg Carroll, Mathis Grossmann, Jeffrey D Zajac and Ada S Cheun

Effectiveness of a nurse practitioner-led cardiovascular prevention clinic at reduction of metabolic syndrome following maternal complications of pregnancy: a preliminary analysis

Aim Maternal complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, intrauterine growth restriction, preterm labour, and placental abruption, are associated with increased risk of future cardiometabolic disease. Lifestyle interventions that focus on preventative strategies for this young, high-risk population of women may assist in cardiometabolic disease risk reduction. The aim of this preliminary registry analysis was to observe the change in maternal metabolic syndrome status after receiving a nurse practitioner-led lifestyle intervention delivered soon after a complicated pregnancy. Method This preliminary analysis included 64 eligible women who had attended both baseline (approximately 6 months postpartum) and review (approximately eighteen months postpartum) appointments at the postpartum lifestyle clinic after an index pregnancy complicated by at least one maternal complication of pregnancy. Metabolic syndrome status at both appointments was assessed. Results At the baseline appointment, 22 (34.4%) women met the criteria for metabolic syndrome. This number reduced at the review appointment to 19 (29.7%). This difference was not statistically significant. There were some modest improvements in the individual cardiometabolic risk factors, as well as marked improvements in the women who had recovered from metabolic syndrome over twelve months Conclusion There was a high percentage of metabolic syndrome present early in the postpartum period. The results of this preliminary analysis highlight the importance of continuing preventative care and ongoing research for this group of high-risk women.Emily Aldridge, Maleesa Pathirana, Melanie Wittwer, Susan Sierp, Shalem Y. Leemaqz, Claire T. Roberts, Gustaaf A. Dekker, and Margaret A. Arstal

A prospective registry analysis of psychosocial and metabolic health between women with and without metabolic syndrome after a complicated pregnancy

Purpose: Pregnancy complications afect over one quarter of Australian pregnancies, and this group of mothers is vulnerable and more likely to experience adverse cardiometabolic health outcomes in the postpartum period. Metabolic syndrome is common in this population and may be associated with postpartum mental health issues. However, this relationship remains poorly understood. To compare the diferences in psychosocial parameters and mental health outcomes between women with metabolic syndrome and women without metabolic syndrome 6 months after a complicated pregnancy. Methods: This study is prospective registry analysis of women attending a postpartum healthy lifestyle clinic 6 months following a complicated pregnancy. Mental health measures included 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalised Anxiety Disorder questionnaire (GAD-7), self-reported diagnosed history of depression, anxiety and/or other psychiatric condition, and current psychotropic medication use. Results: Women with metabolic syndrome reported signifcantly more subjective mental health concerns, were more likely to have a history of depression and other psychiatric diagnoses and were more likely prescribed psychotropic medications. However, there were no signifcant diferences in PHQ-9 and GAD-7 scores. Conclusion: Amongst new mothers who experienced complications of pregnancy, those with metabolic syndrome represent a particularly vulnerable group with regards to psychosocial disadvantage and mental health outcomes. These vulnerabilities may not be apparent when using common standardised cross-sectional mental health screening tools such as PHQ-9 and GAD-7.Emily Aldridge, K. Oliver Schubert, Maleesa Pathirana, Susan Sierp, Shalem Y. Leemaqz, Claire T. Roberts, Gustaaf A. Dekker, and Margaret A. Arstal

DraculR: A Web-Based Application for In Silico Haemolysis Detection in High-Throughput microRNA Sequencing Data

The search for novel microRNA (miRNA) biomarkers in plasma is hampered by haemolysis, the lysis and subsequent release of red blood cell contents, including miRNAs, into surrounding fluid. The biomarker potential of miRNAs comes in part from their multicompartment origin and the longlived nature of miRNA transcripts in plasma, giving researchers a functional window for tissues that are otherwise difficult or disadvantageous to sample. The inclusion of red-blood-cell-derived miRNA transcripts in downstream analysis introduces a source of error that is difficult to identify posthoc and may lead to spurious results. Where access to a physical specimen is not possible, our tool will provide an in silico approach to haemolysis prediction. We present DraculR, an interactive Shiny/R application that enables a user to upload miRNA expression data from a short-read sequencing of human plasma as a raw read counts table and interactively calculate a metric that indicates the degree of haemolysis contamination. The code, DraculR web tool and its tutorial are freely available as detailed herein.Melanie D. Smith, Shalem Y. Leemaqz, Tanja Jankovic-Karasoulos, Dylan McCullough, Dale McAninch, Anya L. Arthurs, James Breen, Claire T. Roberts, and Katherine A. Pillma

Gestational diabetes mellitus and cardio-metabolic risk factors in women and children at 3 years postpartum

Introduction: Gestational diabetes mellitus (GDM) is thought to be associated with cardio-metabolic risk factor development in women and their children during the early postpartum period and early childhood. We hypothesized that these women and their children would exhibit increased abnormal cardio-metabolic risk factors three years after pregnancy. Methods: Women from the Screening Tests to Predict Poor Outcomes of Pregnancy study were invited to attend a followup with the child from their index pregnancy at 3 years postpartum. Women and children were assessed for anthropometric measures and haemodynamic function. Fasting blood samples were obtained from women to assess lipid and glucose status. Results: A total of 281 woman-child dyads participated in the 3-year follow-up, with 40 women developing GDM during their index pregnancy. Fasting serum insulin was higher in women with GDM in index pregnancy compared to those with an uncomplicated pregnancy. However, this association was mediated by early pregnancy BMI and socioeconomic index (SEI). The rate of metabolic syndrome was higher in the GDM group than the uncomplicated pregnancy group. Maternal GDM was associated with elevated maternal fasting serum triglycerides at 3 years after adjustment for early pregnancy BMI and SEI. Children exposed to GDM in utero had higher waist circumference compared to children born after an uncomplicated pregnancy, but this is mediated the above covariates. Conclusion: Exposure to GDM is associated with elevated serum triglycerides in women at 3 years postpartum but other cardiometabolic outcomes in women and children appear to be mediated by early pregnancy BMI and SEI.Maleesa M. Pathirana, Prabha H. Andraweera, Emily Aldridge, Shalem Y. Leemaqz, Madeline Harrison, Jade Harrison, Petra E. Verburg, Margaret A. Arstall, Gustaaf A. Dekker, Claire T. Robert

Bone microarchitecture in transgender adults: a cross-sectional study

First published: 03 January 2022Gender-affirming hormone therapy aligns physical characteristics with an individual’s gender identity, but sex hormones regulate bone remodeling and influence bonemorphology. Wehypothesized that transmen receiving testosterone have compromised bonemorphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti-androgen therapy, have preserved bonemicroarchitecture.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 cismale controls. Between-group differences were expressed as standardized deviations (SD) fromthemean 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 cismen, trans women had 0.68 SD lower total vBMD (p=0.01). Cortical vBMD was 0.70 SD lower (p < 0.01), cortical thicknesswas 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, bonemicroarchitecture 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.Ingrid Bretherton, Ali Ghasem-Zadeh, Shalem Y Leemaqz, Ego Seeman, Xiaofang Wang, Thomas McFarlane, Cassandra Spanos, Mathis Grossmann, Jeffrey D Zajac, and Ada S Cheun

Pelvic Pain in Transgender People Using Testosterone Therapy

Purpose: This descriptive study aimed to assess the characteristics of pelvic pain and explore predictive factors for pelvic pain in transgender (trans) individuals using testosterone therapy. Methods: An online cross-sectional survey was open between August 28, 2020, and December 31, 2020, to trans people presumed female at birth, using testosterone for gender affirmation, living in Australia, and >16 years of age. The survey explored characteristics of pelvic pain following initiation of testosterone therapy, type and length of testosterone therapy, menstruation history, and relevant sexual, gynecological, and mental health experiences. Logistic regression was applied to estimate the effect size of possible factors contributing to pain after starting testosterone. Results: Among 486 participants (median age = 27 years), 351 (72.2%)* reported experiencing pelvic pain following initiation of testosterone therapy, described most commonly as in the suprapubic region and as ‘‘cramping.’’ Median duration of testosterone therapy was 32 months. Persistent menstruation, current or previous history of post-traumatic stress disorder, and experiences of pain with orgasm were associated with higher odds of pelvic pain after testosterone therapy. No association was observed with genital dryness, intrauterine device use, previous pregnancy, penetrative sexual activities, touching external genitalia, or known diagnoses of endometriosis, vulvodynia, vaginismus, depression, anxiety, or obesity. Conclusions: Pelvic pain is frequently reported in trans people following initiation of testosterone therapy. Given the association with persistent menstruation and orgasm, as well as the known androgen sensitivity of the pelvic floor musculature, further research into pelvic floor muscle dysfunction as a contributor is warranted.Sav Zwickl, Laura Burchill, Alex Fang Qi Wong, Shalem Y. Leemaqz, Teddy Cook, Lachlan M. Angus, Kalen Eshin, Charlotte V. Elder, Sonia R. Grover, Jeffrey D. Zajac, and Ada S. Cheun

Maternal selenium, copper and zinc concentrations in early pregnancy, and the association with fertility

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks' gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99-1.44)) or who had lower selenium concentrations (1.19 (1.01-1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06-2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.Jessica A. Grieger, Luke E. Grzeskowiak, Rebecca L. Wilson, Tina Bianco-Miotto, Shalem Y. Leemaqz, Tanja Jankovic-Karasoulos, Anthony V. Perkins, Robert J. Norman, Gus A. Dekker and Claire T. Robert

Maternal folate, one-carbon metabolism and pregnancy outcomes

Single nucleotide polymorphisms and pre- and peri-conception folic acid (FA) supplementation and dietary data were used to identify one-carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 μg daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 μg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L-1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre- and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.Tanja Jankovic-Karasoulos, Denise L. Furness, Shalem Y. Leemaqz, Gustaaf A. Dekker, Luke E. Grzeskowiak, Jessica A. Grieger, Prabha H. Andraweera, Dylan McCullough, Dale McAninch, Lesley M. McCowan, Tina Bianco-Miotto, Claire T. Robert