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

Fluctuating Elastic Rings: Statics and Dynamics

We study the effects of thermal fluctuations on elastic rings. Analytical expressions are derived for correlation functions of Euler angles, mean square distance between points on the ring contour, radius of gyration, and probability distribution of writhe fluctuations. Since fluctuation amplitudes diverge in the limit of vanishing twist rigidity, twist elasticity is essential for the description of fluctuating rings. We find a crossover from a small scale regime in which the filament behaves as a straight rod, to a large scale regime in which spontaneous curvature is important and twist rigidity affects the spatial configurations of the ring. The fluctuation-dissipation relation between correlation functions of Euler angles and response functions, is used to study the deformation of the ring by external forces. The effects of inertia and dissipation on the relaxation of temporal correlations of writhe fluctuations, are analyzed using Langevin dynamics.Comment: 43 pages, 9 Figure

Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy

BACKGROUND:Estradiol with or without an antiandrogen (cyproterone acetate or spironolactone) is commonly prescribed in transfeminine individuals who have not had orchidectomy, however there is no evidence to guide optimal treatment choice. OBJECTIVE:We aimed to compare add-on cyproterone acetate versus spironolactone in lowering endogenous testosterone concentrations in transfeminine individuals. DESIGN:Retrospective cross-sectional study. METHODS:We analysed 114 transfeminine individuals who had been on estradiol therapy for >6 months in two gender clinics in Melbourne, Australia. Total testosterone concentrations were compared between three groups; estradiol alone (n=21), estradiol plus cyproterone acetate (n=21) and estradiol plus spironolactone (n=38). Secondary outcomes included serum estradiol concentration, estradiol valerate dose, blood pressure, serum potassium, urea and creatinine. RESULTS:Median age was 27.0 years (22.5, 45.1) and median duration of hormone therapy was 1.5 years (0.9, 2.6), which was not different between groups. On univariate analysis, the cyproterone group had significantly lower total testosterone concentrations (0.8nmol/L (0.6, 1.20)) compared with the spironolactone group (2.0nmol/L (0.9, 9.4), p=0.037) and estradiol alone group (10.5nmol/L (4.9, 17.2), p<0.001), which remained significant (p=0.005) after adjustments for estradiol concentration, dose and age. Serum urea was higher in the spironolactone group compared with the cyproterone group. No differences were observed in total daily estradiol dose, blood pressure, serum estradiol, potassium or creatinine. CONCLUSIONS:The cyproterone group achieved serum total testosterone concentrations in the female reference range. As spironolactone may cause feminisation without inhibition of steroidogenesis, it is unclear which anti-androgen is more effective at feminisation. Further prospective studies are required.Lachlan Angus, Shalem Leemaqz, Olivia Ooi, Pauline Cundill, Nicholas Silberstein, Peter Locke, Jeffrey D Zajac and Ada S Cheun

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

Growth Based Morphogenesis of Vertebrate Limb Bud

Many genes and their regulatory relationships are involved in developmental phenomena. However, by chemical information alone, we cannot fully understand changing organ morphologies through tissue growth because deformation and growth of the organ are essentially mechanical processes. Here, we develop a mathematical model to describe the change of organ morphologies through cell proliferation. Our basic idea is that the proper specification of localized volume source (e.g., cell proliferation) is able to guide organ morphogenesis, and that the specification is given by chemical gradients. We call this idea “growth-based morphogenesis.” We find that this morphogenetic mechanism works if the tissue is elastic for small deformation and plastic for large deformation. To illustrate our concept, we study the development of vertebrate limb buds, in which a limb bud protrudes from a flat lateral plate and extends distally in a self-organized manner. We show how the proportion of limb bud shape depends on different parameters and also show the conditions needed for normal morphogenesis, which can explain abnormal morphology of some mutants. We believe that the ideas shown in the present paper are useful for the morphogenesis of other organs