A Rose by Any Other Name: Gender-Affirming Care and Severe Mental Illness

The transgender population has higher rates of psychiatric disorders and stigma within medical settings. Literature suggests that gender-affirming care is the standard when working with such patients. There are limited studies regarding treating these patients with severe mental illness (SMI). This article explores how to treat SMI that impacts patients' reality to the point where their assigned sex cannot be acknowledged. The case presented is that of a transgender woman, where clarification of her natal sex was crucial to treatment. The patient denied her natal sex, endorsing a history of miscarriage. Studies on treatment of transgender SMI patients are limited. Gender-affirming treatment is the standard of care for these patients. Training how to ask pertinent questions and communicate effectively is necessary to prevent misdiagnosis, unnecessary treatment, and agitation. [Psychiatr Ann. 2023;53(5):221–223.]

Antioxidant and Anti-Breast Cancer Properties of Hyaluronidase from Marine Staphylococcus aureus (CASMTK1)

This work studied the antioxidant and anti-breast cancer properties of hyaluronidase, extracted from a potential marine strain, Staphylococcus aureus (CASMTK1), isolated from Parangipettai coastal waters in southeast coast of India. The Staphylococcal enzyme production was tested under different carbon and nitrogen sources;and recorded the maximum production when the microbial strain was cultured with starch as the carbon source and ammonium sulphate as the inorganic nitrogen source with the enzyme production of 92.5 U/mL and 95.0 U/mL, respectively. The hyaluronidase enzyme production was also tested in different pH and temperature;and recorded the maximum yield of 102.5 U/mL in pH 5 and that of 95.5 U/mL in 45 °C. The partially purified enzyme was subjected to FTIR and FT Raman technique and found the presence of the amide- I and II, Carboxyl, N-H bending, C-H stretching and α-helices and β-sheet proteins between wave number 1500–1700 cm−1. The partially purified enzyme also exhibited strong antioxidant and in-vitro breast cancer properties. The enzyme showed the highest hydroxyl radical scavenging activity of 79% at the 50 µg/mL concentration, and this activity increased in a dose-dependent manner. The enzyme inhibited proliferation of the breast cancer cell line of MCF-7, and it caused 100% cell death at the concentration of 80 µg/mL. The enzyme generated capacity of producing free radicles that damage the cancer cells, and this effect was very nearer to the standard drug, paclitaxel. The enzyme damaged the cancer cells and induced apoptosis in 78% of cancer cells as evident by condensed or fragmented chromatin at 40 µg/mL. Further purification of the enzyme, analysis of its molecular aspects, and elucidation of exact mechanisms of its biological activities will throw new light on the utility of staphylococcal hyaluronidase in anticancer chemotherapy.

Hormone replacement therapy and COVID-19 outcomes in solid organ transplant recipients compared with the general population.

Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation.

Case Report: Induced Lactation in an Adoptive Parent

Letters

To study the effect of six months of combined estrogen and progestin treatment on anti-mullerian hormone in polycystic ovary syndrome patients

Background: Anti-Mullerian hormone (AMH) is secreted by small antral follicles and is elevated in PCOS. Unlike serum total testosterone, its value remains constant irrespective of the phase of menstrual cycle. Serum AMH could prove to be a promising marker of disease activity and response to therapy. Combined estrogen-progestin (CEP) pills are considered treatment of choice in PCOS, but their effect on serum AMH has not been widely studied. Objective: To study the effect of six months of CEP pills on serum AMH and testosterone in PCOS patients. Methods: 55 consecutive females, above 18 years and diagnosed with PCOSby Rotterdam Criteria, who attended our outpatient clinic from July 2020 to April 2021, were enrolled. Hirsutism was assessed by modified Ferriman-Gallwey Scoring (mFGS). Serum AMH and total testosterone were measured at baseline, and all the patients were initiated on combination of ethinyl estradiol (35 mcg) with cyproterone acetate (2 mg), to be taken orally for 21 days every month for a period of 6 months. Serum AMH and total testosterone were reassessed again after 6 months of CEP therapy. Out of total 55 patients, 14 were lost to follow up due to Covid-19 pandemic. A total of 24 patients completed 6 months of CEP therapy, while remaining discontinued the treatment after a mean period of 2 months because of perceived adverse effects. Results: Mean age of study population was 22.8 ± 4.4 years. At baseline, hyperandrogenic features like acne, hirsutism and hair fall were present in 41 (74.5%), 35 (63.6%) and 42 (76.4%) females, respectively. Mean mFGS was 5.6 ± 2.8. Oligomenorrhoea was reported by38 (69.1%) females. Mean AMH levels and testosterone were 12.1 ± 7.1 ng/ml and 46.6 ± 20.1 ng/dl, respectively. There were 17 (30.9%) patients who had testosterone 360 ng/dl, while 42 females (76.3%) had high AMH levels (36.8 ng/ml). Baseline AMH positively correlated with BMI and serum LH level. Post-treatment, there was significant decrease inacne, hirsutism and hair fall (P < 0.001 for all). Mean mFGS (5.6 ± 2.8 vs 4.2 ± 2, P < 0.001) and mean serum AMH levels (12.1 ± 7.1 ng/ml vs 10.4 ± 7 ng/ml, P = 0.002) demonstrated a significant improvement. Serum testosterone levels decreased post therapy (46.6 ± 20.1 vs 42.3 ± 17.4 ng/dl, P = 0.08), but did not reach statistical significance (table 1). Testosterone and AMH levels did not show any correlation (R = 0.054, P = 0.7). Conclusions: AMH levels show a significant decline after 6 months of treatment, corresponding to improvement in hyperandrogenic symptoms and mFGS. AMH can prove to be a promising marker of disease activity in PCOS. The major limitation of the study was its small sample size, and more robust studies are needed.

Hormonal therapies and venous thrombosis: Considerations for prevention and management.

Background: Venous thromboses are well-established complications of hormonal therapy. Thrombosis risk is seen with both hormonal contraceptive agents and with hormone replacement therapy for menopause and gender transition. Over the past several decades, large epidemiological studies have helped better define these risks. Objectives: To review and discuss the differences in thrombosis risk of the many of hormonal preparations available as well as their interaction with patient-specific factors. Methods: We conducted a narrative review of the available literature regarding venous thrombosis and hormonal therapies including for contraception, menopausal symptoms, and gender transition. Results: Thrombosis risk with estrogen-containing compounds increases with increasing systemic dose of estrogen. While progesterone-only-containing products are not associated with thrombosis, when paired with estrogen in combined oral contraceptives, the formulation of progesterone does impact the risk. These components, along with patient-specific factors, may influence the choice of hormonal preparation. For patients who develop thrombosis on hormonal treatment, anticoagulation is protective against future thrombosis. Duration of anticoagulation is dependent on ongoing and future hormone therapy choice. Finally, the optimal management of hormone therapy for individuals diagnosed with prothrombotic illnesses such as COVID-19 remains unclear. Conclusions: When contemplating hormonal contraception or hormone replacement therapy, clinicians must consider a variety of factors including hormone type, dose, route, personal and family history of thrombosis, and other prothrombotic risk factors to make informed, personalized decisions regarding the risk of venous thrombosis.

Effect of Norelgestromin and Ethinylestradiol in Transdermal Patches on the Clinical Outcomes and Biochemical Parameters of COVID-19 Patients: A Clinical Trial Pilot Study.

The disease caused by SARS-CoV-2 is still considered a global pandemic. Transdermal patches (TP) with immunoregulators such as estrogen and progesterone compounds could be a feasible option to treat COVID-19 because of their accessibility and relative safety. The objective of the current study was to evaluate the additional treatment with norelgestromin and ethinylestradiol in TP on the clinical and biochemical evolution of COVID-19 patients. The present is a clinical-trial pilot study that included subjects diagnosed with COVID-19, randomized into two groups; the experimental Evra® TP (norelgestromin 6 mg and ethinylestradiol 0.60 mg) was administered such that it was applied on arrival and replaced at day 8 and day 15. The control continued with the conventional COVID-19 treatment protocol. A blood sample was taken each week in order to evaluate relevant biochemical parameters, clinical signs, and evolution. In total, 44 subjects participated in this study, 30 in the experimental group and 14 in the control group. Both groups were homogeneous in terms of age and comorbidities. The experimental group had a significantly lower hospital stay (p = 0.01), high flow supplemental oxygen (p = 0.001), mechanical ventilation (p = 0.003), and intubation (p = 0.01), and the oxygen saturation significantly increased (p = 0.01) in comparison with control group when patients were exposed to room air. A decrease in ferritin (p < 0.05) was observed, with no significant increase in ESR (p > 0.05), D dimer (p > 0.05) and platelets (p > 0.05) in an auto-controlled analysis in the experimental group. Norelgestromin and ethinylestradiol TP could be a safe and effective treatment for moderate and severe COVID-19 patients.

Are sex hormones promising candidates to explain sex disparities in the COVID-19 pandemic?

Emerging evidence suggests that the novel Coronavirus disease-2019 (COVID-19) is deadlier for men than women both in China and in Europe. Male sex is a risk factor for COVID-19 mortality. The meccanisms underlying the reduced morbidity and lethality in women are currently unclear, even though hypotheses have been posed (Brandi and Giustina in Trends Endocrinol Metab. 31:918-27, 2020). This article aims to describe the role of sex hormones in sex- and gender-related fatality of COVID-19. We discuss the possibility that potential sex-specific mechanisms modulating the course of the disease include both the androgen- and the estrogen-response cascade. Sex hormones regulate the respiratory function, the innate and adaptive immune responses, the immunoaging, the cardiovascular system, and the entrance of the virus in the cells. Recommendations for the future government policies and for the management of COVID-19 patients should include a dimorphic approach for males and females. As the estrogen receptor signaling appears critical for protection in women, more studies are needed to translate the basic knowledge into clinical actions. Understanding the etiological bases of sexual dimorphism in COVID-19 could help develop more effective strategies in individual patients in both sexes, including designing a good vaccine.

Understanding the Role of Estrogen Receptor Status in PRODH/POX-Dependent Apoptosis/Survival in Breast Cancer Cells.

It has been suggested that activation of estrogen receptor α (ER α) stimulates cell proliferation. In contrast, estrogen receptor ß (ER ß) has anti-proliferative and pro-apoptotic activity. Although the role of estrogens in estrogen receptor-positive breast cancer progression has been well established, the mechanism of their effect on apoptosis is not fully understood. It has been considered that ER status of breast cancer cells and estrogen availability might determine proline dehydrogenase/proline oxidase (PRODH/POX)-dependent apoptosis. PRODH/POX is a mitochondrial enzyme that converts proline into pyrroline-5-carboxylate (P5C). During this process, ATP (adenosine triphosphate) or ROS (reactive oxygen species) are produced, facilitating cell survival or death, respectively. However, the critical factor in driving PRODH/POX-dependent functions is proline availability. The amount of this amino acid is regulated at the level of prolidase (proline releasing enzyme), collagen biosynthesis (proline utilizing process), and glutamine, glutamate, α-ketoglutarate, and ornithine metabolism. Estrogens were found to upregulate prolidase activity and collagen biosynthesis. It seems that in estrogen receptor-positive breast cancer cells, prolidase supports proline for collagen biosynthesis, limiting its availability for PRODH/POX-dependent apoptosis. Moreover, lack of free proline (known to upregulate the transcriptional activity of hypoxia-inducible factor 1, HIF-1) contributes to downregulation of HIF-1-dependent pro-survival activity. The complex regulatory mechanism also involves PRODH/POX expression and activity. It is induced transcriptionally by p53 and post-transcriptionally by AMPK (AMP-activated protein kinase), which is regulated by ERs. The review also discusses the role of interconversion of proline/glutamate/ornithine in supporting proline to PRODH/POX-dependent functions. The data suggest that PRODH/POX-induced apoptosis is dependent on ER status in breast cancer cells.

Bioboard

The following topics are under this section:ASIA-PACIFIC — Identification of Therapeutic Points for Genetically Diverse and Fatal LeukaemiaASIA-PACIFIC — Novel Microfluidic Processes for Drug DevelopmentASIA-PACIFIC — Development of Anti-Microbial Coating against COVID-19ASIA-PACIFIC — Partnership between Arcturus Therapeutics and Duke-NUS Medical School to develop COVID-19 VaccineASIA-PACIFIC — Nanoscopic Insights to Proteins against Huntington’s DiseaseASIA-PACIFIC — Unravelling the Impact of Marine Heatwave on Coral Reef FishesASIA-PACIFIC — Regulation of Plant Pores by MicroRNAsASIA-PACIFIC — Discovering Clues to Longevity in Our GenomeASIA-PACIFIC — Repurposing Nature’s Products to Viable MaterialsASIA-PACIFIC — Reverse Conversion of Oestrogens to AndrogensREST OF THE WORLD — HER2-targeted Antibody Drug Conjugate Shows Promise in Patients with Non-Breast-Gastric CancersREST OF THE WORLD — New Research finds Teeth as a Biological ArchiveREST OF THE WORLD — Finding Treatment for Muscular Dystrophy using CRISPR

Men with COVID-19 die. Women survive.

The severity and mortality rate of COVID-19 differ between the sexes. Several biopsychosocial determinants may account for the better outcomes in women. The notion that sex steroid hormones account for the gender disparity is reasonable but not proven; the same is true of the role of menopause as a risk factor. A retrospective analysis of patients (=1764) hospitalized in Italy showed a higher mortality (HR 1.58, 95%CI 1.30-1.91, adjusted for age and multi-comorbidities) in males only after the age of 65 (the rate is twice as high in the 65-79-year age group and 1.5-fold higher in those aged over 80). The higher mortality of men is mostly evident among those aged over 65 years, long after the average age of menopause.

Roles of steroid receptors in the lung and COVID-19.

COVID-19 symptoms and mortality are largely due to its devastating effects in the lungs. The disease is caused by the SARS (Severe Acute Respiratory Syndrome)-CoV-2 coronavirus, which requires host cell proteins such as ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) for infection of lung epithelia. The expression and function of the steroid hormone receptor family is important in many aspects that impact on COVID-19 effects in the lung - notably lung development and function, the immune system, and expression of TMPRSS2 and ACE2. This review provides a brief summary of current knowledge on the roles of the steroid hormone receptors [androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), mineralocorticoid receptor (MR) and oestrogen receptor (ER)] in the lung, their effects on host cell proteins that facilitate SARS-CoV-2 uptake, and provides a snapshot of current clinical trials investigating the use of steroid receptor (SR) ligands to treat COVID-19.

Roles of Genetic Predisposition in the Sex Bias of Pulmonary Pathophysiology, as a Function of Estrogens : Sex Matters in the Prevalence of Lung Diseases.

In addition to studies focused on estrogen mediation of sex-different regulation of systemic circulations, there is now increasing clinical relevance and research interests in the pulmonary circulation, in terms of sex differences in the morbidity and mortality of lung diseases such as inherent-, allergic- and inflammatory-based events. Thus, female predisposition to pulmonary artery hypertension (PAH) is an inevitable topic. To better understand the nature of sexual differentiation in the pulmonary circulation, and how heritable factors, in vivo- and/or in vitro-altered estrogen circumstances and changes in the live environment work in concert to discern the sex bias, this chapter reviews pulmonary events characterized by sex-different features, concomitant with exploration of how alterations of genetic expression and estrogen metabolisms trigger the female-predominant pathological signaling. We address the following: PAH (Sect.7.2) is characterized as an estrogenic promotion of its incidence (Sect. 7.2.2), as a function of specific germline mutations, and as an estrogen-elicited protection of its prognosis (Sect.7.2.1). More detail is provided to introduce a less recognized gene of Ephx2 that encodes soluble epoxide hydrolase (sEH) to degrade epoxyeicosatrienic acids (EETs). As a susceptible target of estrogen, Ephx2/sEH expression is downregulated by an estrogen-dependent epigenetic mechanism. Increases in pulmonary EETs then evoke a potentiation of PAH generation, but mitigation of its progression, a phenomenon similar to the estrogen-paradox regulation of PAH. Additionally, the female susceptibility to chronic obstructive pulmonary diseases (Sect. 7.3) and asthma (Sect.7.4), but less preference to COVID-19 (Sect. 7.5), and roles of estrogen in their pathogeneses are briefly discussed.

Sex Disparities in COVID-19 Severity and Outcome: Are Men Weaker or Women Stronger?

The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health issue which has profound effects on most aspects of societal well-being, including physical and mental health. A plethora of studies globally have suggested the existence of a sex disparity in the severity and outcome of COVID-19 patients, mainly due to mechanisms of virus infection, immune response to the virus, development of systemic inflammation, and consequent systemic complications, particularly thromboembolism. Epidemiological data report a sex difference in the severity of COVID-19, with a more favorable course of the disease in women compared to men regardless of age, although the rate of SARS-CoV-2 infection seems to be similar in both sexes. Sex hormones, including androgens and estrogens, may not only impact virus entry and load, but also shape the clinical manifestations, complications, and ultimately the outcome of the disease. The current review comprehensively summarizes the current literature on sex disparities in susceptibility and outcome of COVID-19 as well as the literature underpinning the pathophysiological and molecular mechanisms, which may provide a rationale to a sex disparity. These mechanisms include sex hormone influence on factors that facilitate virus entry and priming, immune and inflammatory response, as well as coagulation and thrombosis diathesis. Based on present evidence, women appear to be relatively protected from COVID-19 because of a more effective immune response and a less pronounced systemic inflammation, with consequent moderate clinical manifestations of the disease, together with a lesser predisposition to thromboembolism. Conversely, men appear to be particularly susceptible to COVID-19 because of a less effective immune response with consequent severe clinical manifestations of the disease, together with a greater predisposition to thromboembolism. In the elderly, generally characterized by the phenomenon of inflammaging, sex disparities in overall mortality following SARS-CoV-2 infection are even more palpable as elderly men appear to be more prone to severe COVID-19 because of a greater predisposition to infections, a weaker immune defense, and an enhanced thrombotic state compared to women. The information revealed from the review highlights potential novel therapeutic approaches employing the administration of hormonal or antihormonal therapy in combination with antiviral drugs in COVID-19 patients.

Gender disparity in COVID-19: Role of sex steroid hormones.

The emerging pandemic of COVID-19 caused by the novel pathogenic human coronavirus SARS-CoV-2 has caused significant morbidity and mortality across the globe, prompting the scientific world to search for preventive measures to interrupt the disease process. Demographic data indicates gender-based differences in COVID-19 morbidity with better outcome amongst females. Disparity in sex-dependent morbidity and mortality in COVID-19 patients may be attributed to difference in levels of sex steroid hormones -androgens and estrogens. Evidence suggests that apart from the regulation of viral host factors, immunomodulatory and cardioprotective roles exerted by estrogen and progesterone may provide protection to females against COVID-19. Exploring the underlying mechanisms and beneficial effects of these hormones as an adjuvant to existing therapy may be a step towards improving the outcomes. This article aims to review studies demonstrating the role of sex steroidal hormones in modulating SARS-CoV-2 host factors and summarize plausible biological reasons for sex-based differences seen in COVID-19 mortality.

Incidence, clinical features, and outcomes of COVID-19 in Canada: impact of sex and age.

Male sex and older age have been reported to be associated with worse outcomes from COVID-19. It was postulated that estrogens may play a role in reducing the severity of the disease and may therefore offer a treatment option for COVID-19 patients. However, more female cases and deaths from COVID-19 have been recorded in Canada. To determine the potential role of estrogens, we analyzed COVID-19 data from Canada, focusing on the impact of sex and age. Although the overall incidence rate is higher in females than in males, when several high risk groups, including health care workers and long-term care residences, which are predominantly females, were excluded, we found that females had a lower incidence rate than males between the ages of 20s to 70s. Interestingly, this sex-based difference is more evident in females of the reproductive ages (20-49) than in postmenopausal patients (60s or older). Males have significantly higher hospitalization, ICU admission, and case fatality rates; however, a greater difference was observed in the older age groups. Finally, symptom manifestation varied between sexes. Some of the symptoms, which were more frequently observed in patients who recovered than patients who died, were more commonly observed in females of the reproductive age compared to their male counterparts. Since only females of the reproductive age have much higher circulating estrogens than males, these findings suggest that estrogens may play a role in reducing COVID-19 incidence and in the development of symptoms, especially those related to better survival.

The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients.

Coronavirus disease-2019 (COVID-19), a disease caused by Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages in the United States, and the highest incidence and mortality in adult men. As the pandemic evolves there is limited understanding of a potential association between symptomatic viral infection and age. To date, there is no knowledge of the role children (prepubescent, ages 9-13 years) play as "silent" vectors of the virus, with themselves being asymptomatic. Throughout different time frames and geographic locations, the current evidence on COVID-19 suggests that children are becoming infected at a significantly lower rate than other age groups-as low as 1%. Androgens upregulate the protease TMPRSS2 (type II transmembrane serine protease-2), which facilitates efficient virus-host cell fusion with the epithelium of the lungs, thus increasing susceptibility to SARS-CoV-2 infection and development of severe COVID-19. Owing to low levels of steroid hormones, prepubertal children may have low expression of TMPRSS2, thereby limiting the viral entry into host cells. As the world anticipates a vaccine against SARS-CoV-2, the role of prepubescent children as vectors transmitting the virus must be interrogated to prepare for a potential resurgence of COVID-19. This review discusses the current evidence on the low incidence of COVID-19 in children and the effect of sex-steroid hormones on SARS-CoV-2 viral infection and clinical outcomes of pediatric patients. On reopening society at large, schools will need to implement heightened health protocols with the knowledge that children as the "silent" viral transmitters can significantly affect the adult populations.

Sex and COVID-19: A Protective Role for Reproductive Steroids.

Evidence shows coronavirus disease 2019 (COVID-19)-induced symptom severity and mortality is more frequent in men than in women, suggesting sex steroids may play a protective role. Female reproductive steroids, estrogen and progesterone, and its metabolite allopregnanolone, are anti-inflammatory, reshape competence of immune cells, stimulate antibody production, and promote proliferation and repair of respiratory epithelial cells, suggesting they may protect against COVID-19 symptoms.