Anabolic-Androgenic Steroid Use in Sports, Health, and Society.

This consensus statement is an update of the 1987 American College of Sports Medicine (ACSM) position stand on the use of anabolic-androgenic steroids (AAS). Substantial data have been collected since the previous position stand, and AAS use patterns have changed significantly. The ACSM acknowledges that lawful and ethical therapeutic use of AAS is now an accepted mainstream treatment for several clinical disorders; however, there is increased recognition that AAS are commonly used illicitly to enhance performance and appearance in several segments of the population, including competitive athletes. The illicit use of AAS by competitive athletes is contrary to the rules and ethics of many sport governing bodies. Thus, the ACSM deplores the illicit use of AAS for athletic and recreational purposes. This consensus statement provides a brief history of AAS use, an update on the science of how we now understand AAS to be working metabolically/biochemically, potential side effects, the prevalence of use among athletes, and the use of AAS in clinical scenarios.

Neonatal programming with sex hormones: Effect on expression of dopamine D1 receptor and neurotransmitters release in nucleus accumbens in adult male and female rats.

Steroid sex hormones produce physiological effects in reproductive and non-reproductive tissues, such as the brain. In the brain, sex hormones receptors are expressed in cortical, limbic and midbrain areas modulating memory, arousal, fear and motivation between other behaviors. One neurotransmitters system regulated by sex hormones is dopamine (DA), where during adulthood, sex hormones promote neurophysiological and behavioral effects on DA systems such as tuberoinfundibular (prolactin secretion), nigrostriatal (motor circuit regulation) and mesocorticolimbic (driving of motivated behavior). However, the long-term effects induced by neonatal exposure to sex hormones on DA release induced by D1 receptor activation and its expression in nucleus accumbens (NAcc) have not been fully studied. To answer this question, neurochemical, cellular and molecular techniques were used. The data show sex differences in NAcc DA extracellular levels induced by D1 receptor activation and protein content of this receptor in male and female control rats. In addition, neonatal programming with a single dose of TP increases the NAcc protein content of D1 receptors of adult male and female rats. Our results show new evidence related with sex differences that could explain the dependence to drug of abuse in males and females, which may be associated with increased reinforcing effects of drugs of abuse.

Thrombosis Risk in Transgender Adolescents Receiving Gender-Affirming Hormone Therapy.

BACKGROUND AND OBJECTIVES: Many transgender youth experience gender dysphoria, a risk factor for suicide. Gender-affirming hormone therapy (GAHT) ameliorates this risk but may increase the risk for thrombosis, as seen from studies in adults. The aim with this study was to examine thrombosis and thrombosis risk factors among an exclusively adolescent and young adult transgender population. METHODS: This retrospective chart review was conducted at a pediatric hospital-associated transgender health clinic. The primary outcome was incidence of arterial or venous thrombosis during GAHT. Secondary measures included the prevalence of thrombosis risk factors. RESULTS: Among 611 participants, 28.8% were transgender women and 68.1% were transgender men. Median age was 17 years at GAHT initiation. Median follow-up time was 554 and 577 days for estrogen and testosterone users, respectively. Individuals starting GAHT had estradiol and testosterone levels titrated to physiologic normal. Multiple thrombotic risk factors were noted among the cohort, including obesity, tobacco use, and personal and family history of thrombosis. Seventeen youth with risk factors for thrombosis were referred for hematologic evaluation. Five individuals were treated with anticoagulation during GAHT: 2 with a previous thrombosis and 3 for thromboprophylaxis. No participant developed thrombosis while on GAHT. CONCLUSIONS: In this study, we examined thrombosis and thrombosis risk factors in an exclusively adolescent and young adult population of transgender people receiving GAHT. These data suggest that GAHT in youth, titrated within physiologic range, does not carry a significant risk of thrombosis in the short-term, even with the presence of preexisting thrombosis risk factors.

Cross-sex hormone treatment and own-body perception: behavioral and brain connectivity profiles.

Referrals for gender dysphoria (GD), characterized by a distressful incongruence between gender identity and at-birth assigned sex, are steadily increasing. The underlying neurobiology, and the mechanisms of the often-beneficial cross-sex hormone treatment are unknown. Here, we test hypothesis that own body perception networks (incorporated in the default mode network-DMN, and partly in the salience network-SN), are different in trans-compared with cis-gender persons. We also investigate whether these networks change with cross-sex hormone treatment. Forty transmen (TrM) and 25 transwomen (TrW) were scanned before and after cross-sex hormone institution. We used our own developed Body Morph test (BM), to assess the perception of own body as self. Fifteen cisgender persons were controls. Within and between-group differences in functional connectivity were calculated using independent components analysis within the DMN, SN, and motor network (a control network). Pretreatment, TrM and TrW scored lower "self" on the BM test than controls. Their functional connections were weaker in the anterior cingulate-, mesial prefrontal-cortex (mPFC), precuneus, the left angular gyrus, and superior parietal cortex of the DMN, and ACC in the SN "Self" identification and connectivity in the mPFC in both TrM and TrW increased from scan 1 to 2, and at scan 2 no group differences remained. The neurobiological underpinnings of GD seem subserved by cerebral structures composing major parts of the DMN.

Mandibular-related bone metabolism in orchiectomized rats treated with sex hormones.

OBJECTIVE: This study aimed to compare the impact of testosterone and estrogen replacement therapy on mandibular bone density and bone-related markers. DESIGN: Forty male adult rats were randomly allocated to 4 experimental groups (n = 10/group): Sham (Control); Orchiectomy; Orchiectomy plus testosterone replacement; and orchiectomy plus estradiol replacement. Twenty-four days after orchiectomy, the hemi-mandibles were collected and processed for analysis of microhardness in cortical and trabecular bone, radiographic bone density and histomorphometric evaluation. Serum was collected for the analysis of calcium, phosphorus, alkaline phosphatase and magnesium. RESULTS: The orchiectomy group had the lowest mandibular bone density (p < 0.01) and also their serum levels of alkaline phosphatase were higher than all other experimental groups (p < 0.001). Estradiol replacement significantly reduced microhardness when compared to orchiectomy in cortical bone (p < 0.05). Both testosterone and estrogen replacement reverted orchiectomy impact on this parameter (p < 0.01); and decreased alkaline phosphatase to levels comparable to the Sham-Control group. The effect of estrogen was more pronounced than testosterone, and a statistically significant difference was observed between Sham-Control and testosterone replacement (p < 0.05) but not between Sham-Control and estradiol replacement groups. CONCLUSION: Our findings demonstrated that both estradiol and testosterone replacement therapies play a role in mandibular bone metabolism, but suggest different pathways.

Metabolic effects of cross-sex hormone therapy in transgender individuals in Taiwan.

BACKGROUND: Transgender individuals often require gender-affirming interventions, such as endogenous sex hormone inhibition or gender-affirming hormone therapy (HT), while there is discordance between their body and gender identity. However, a recent study found that the incidence of cardiovascular events is higher in transgender patients receiving cross-sex HT. The aim of this study was to investigate the metabolic effects of an altered sex hormone profile. METHODS: This retrospective study, conducted in a referral center in Northern Taiwan, analyzed metabolic changes over time in 65 trans masculine and 45 trans feminine persons. The transgender individuals were examined at 4 time points: before the gender affirming HT, as well as 3, 6, and 12 months following treatment. RESULTS: Compared with baseline measurements, the trans masculine patients showed significant increases in body mass index (BMI) (22.6 ± 0.3 vs 23.3 ± 0.4 kg/m2; p < 0.001; t = 3M), low-density lipoprotein cholesterol (124.3 ± 3.7 vs 131.3 ± 3.9 mg/dL; p = 0.03; t = 12M), creatinine (0.75 ± 0.01 vs 0.83 ± 0.14 mg/dL; p < 0.001; t = 12M), and hemoglobin (13.5 ± 0.7 vs 15.2 ± 0.2 g/dL; p < 0.001; t = 12M), as well as decreased high-density lipoprotein cholesterol (57 ± 2.1 vs 51 ± 2.0 mg/dL; p < 0.001; t = 12M). The trans feminine patients had reduced low-density lipoprotein cholesterol (104.2 ± 3.2 vs 100.8 ± 3.5 mg/dL; p = 0.05; t = 3M), hemoglobin (14.0 ± 0.1 vs 13.5 ± 0.1 g/dL; p = 0.008; t = 12M), and creatinine (0.82 ± 0.01 vs 0.79 ± 0.14 mg/dL; p < 0.001; t = 3M) compared with baseline data. In addition, most of these metabolic effects persisted during the follow-up period. CONCLUSION: This observational, retrospective study revealed that gender-affirming HT increased the relative cardiovascular risk in trans masculine individuals.

Adult Gender Dysphoria with Coronary Disease. Case Report and Literature Review. / Disforia de género en el adulto con enfermedad coronaria. Reporte de caso y revisión de la literatura.

INTRODUCTION: Gender dysphoria (GD) refers to a marked incongruity between gender identity and biological sex. GD generates a significant clinical discomfort for at least six months. METHODS: Case report and non-systematic literature review. Case presentation A 56-year-old male-to-female patient, who had a history of coronary disease and a second thromboembolic event after hormone therapy (self-medicated). Once she had received acute management for the cardiovascular disease, she consulted for her GD. DISCUSSION: GD requires multidisciplinary management. Cross-sex hormonal therapy is considered the main treatment. It has been documented that oral oestrogen preparations may increase the risk of thromboembolic events in patients over the age of 40, especially when they have cardiovascular risk factors. CONCLUSIONS: Comprehensive treatment should be offered to everyone who has GD, to relieve psychological distress, decrease psychiatric comorbidity and improve quality of life. To date, there is little scientific evidence regarding cross-sex hormonal therapy in transgender women over the age of 40; we therefore recommend multidisciplinary, close and rigorous monitoring, in particular when they have cardiovascular risk.

The Role of Hormone Stimulation in Men With Nonobstructive Azoospermia Undergoing Surgical Sperm Retrieval.

Nonobstructive azoospermia, (NOA) is the most common cause of azoospermia. NOA is characterized by hypergonadotropic hypogonadism, testicular failure, and impaired spermatogenesis. The recent development of surgical sperm retrieval techniques such as microsurgical testicular sperm extraction (mTESE) has, for the first time, allowed some men with NOA to father biological children. It is common practice for endocrine stimulation therapies such as gonadotropins, selective estrogen receptor modulators (SERMs), and aromatase inhibitors to be used prior to mTESE to increase intratesticular testosterone synthesis with the aim of improving sperm retrieval rates; however, there is currently a paucity of data underpinning their safety and efficacy. We present 2 cases of men with NOA undergoing endocrine stimulation therapy and mTESE. We also discuss the current evidence and controversies associated with the use of hormonal stimulation therapy in couples affected by this severe form of male infertility.

Drug Interactions with Gender-Affirming Hormone Therapy: Focus on Antiretrovirals and Direct Acting Antivirals.

INTRODUCTION: Gender-affirming care may include hormonal therapy to attain desired health outcomes in transgender (trans) individuals. To provide safe, affirming medical care for trans patients, health care providers must identify and manage drug-drug interactions (DDIs) between gender affirming hormonal therapy (GAHT) and other medication therapies. AREAS COVERED: This review summarizes available data on DDIs between GAHT and antiretrovirals (ARVs) or hepatitis C direct acting antivirals (DAAs). Potential pharmacokinetic and pharmacodynamic DDIs are predicted based on GAHT, ARV, and DAA pharmacology and adverse event profiles. Clinical management strategies are discussed. EXPERT OPINION: GAHT may be involved in pharmacokinetic and/or pharmacodynamic DDIs. Certain ARV classes (non-nucleoside reverse transcriptase inhibitors, protease inhibitors) may alter GAHT disposition, whereas selected ARVs (unboosted integrase inhibitors, doravirine, or rilpivirine) may have less impact on GAHT. DAAs may interact with GAHT, but the clinical relevance is unclear. ARV- and/or DAA-associated side effects (including depression, cardiovascular disease, hyperlipidemia) are important to consider in the clinical management of trans patients. Clinicians must evaluate potential DDIs and overlapping side effects between ARVs, DAAs and GAHT when providing care for trans patients.

Providing gender-affirming hormone therapy through primary care: service users.

INTRODUCTION Primary health care providers are playing an increasingly important role in providing gender-affirming health care for gender diverse people. This article explores the experiences of a primary care-based pilot clinic providing gender-affirming hormone therapy in Wellington, New Zealand. AIM To evaluate service users' and health professionals' experiences of a pilot clinic at Mauri Ora (Victoria University of Wellington's Student Health and Counselling Service) that provided gender-affirming hormones through primary care. METHODS In-depth interviews were conducted with four (out of six) service users and four health professionals about their perspectives on the clinic. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS Three themes were identified in service users' interviews, who discussed receiving affirming care due to the clinic's accessibility, relationship-centred care and timeliness. Three themes were identified in the health professionals' interviews, who described how the clinic involves partnership, affirms users' gender and agency, and is adaptable to other primary care settings. Both service users and health professionals discussed concerns about the lack of adequate funding for primary care services and the tensions between addressing mental health needs and accessing timely care. DISCUSSION The experiences of service users and health professionals confirm the value of providing gender-affirming hormone therapy in primary care. Models based in primary care are likely to increase accessibility, depathologise gender diversity and reduce wait times.

European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction".

BACKGROUND: There is a general lack of recommendations for and basic information tailored at sexologists and other health-care professionals for when they encounter trans people in their practice. AIM: We present to clinicians an up-to-date overview of clinical consensus statements on trans health care with attention for sexual function and satisfaction. METHODS: The task force consisted of 7 clinicians experienced in trans health care, selected among European Society for Sexual Medicine (ESSM) scientific committee. The consensus was guided by clinical experience and a review of the available literature and by interactive discussions on trans health, with attention for sexual function and satisfaction where available. OUTCOMES: The foci of the study are assessment and hormonal aspects of trans health care. RESULTS: As the available literature for direct recommendations was limited, most of the literature was used as background or indirect evidence. Clinical consensus statements were developed based on clinical experiences and the available literature. With the multiple barriers to care that many trans people experience, basic care principles still need to be stressed. We recommend that health-care professionals (HCPs) working with trans people recognize the diversity of genders, including male, female, and nonbinary individuals. In addition, HCPs assessing gender diverse children and adolescents should take a developmental approach that acknowledges the difference between prepubescent gender diverse children and pubescent gender diverse adolescents and trans adults. Furthermore, trans people seeking gender-affirming medical interventions should be assessed by HCPs with expertise in trans health care and gender-affirming psychological practice. If masculinization is desired, testosterone therapy with monitoring of serum sex steroid levels and signs of virilization is recommended. Similarly, if feminization is desired, we recommend estrogens and/or antiandrogen therapy with monitoring of serum sex steroid levels and signs of feminization. HCPs should be aware of the influence of hormonal therapy on sexual functioning and satisfaction. We recommend HCPs be aware of potential sexual problems during all surgical phases of treatment. CLINICAL IMPLICATIONS: This is an up-to-date ESSM position statement. STRENGTHS & LIMITATIONS: These statements are based on the data that are currently available; however, it is vital to recognize that this is a rapidly changing field and that the literature, particularly in the field of sexual functioning and satisfaction, is limited. CONCLUSION: This ESSM position statement provides relevant information and references to existing clinical guidelines with the aim of informing relevant HCPs on best practices when working with transgender people. T'Sjoen G, Arcelus J, De Vries ALC, et al. European Society for Sexual Medicine Position Statement "Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction". J Sex Med 2020;17:570-584.

Sudden sex hormone withdrawal and the effects on body composition in late pubertal adolescents with gender dysphoria.

Background Sex hormones initiate profound physical and physiological changes during the pubertal process, but to what extent are they responsible for continuing the body composition changes of late adolescence and what happens to body composition on sudden sex hormone withdrawal? Methods Thirty-six healthy, phenotypically and chromosomally normal late and post-pubertal individuals aged 15-17 years with gender dysphoria (transgirls - birth-registered males identifying as female n = 11; and transboys - birth-registered females identifying as male n = 25) underwent Tanita body composition analysis at 0, 6 and 12 months during reproductive hormone suppression with Triptorelin as part of the standard therapeutic protocol. Results and conclusions In the transgirl cohort, paired t-test analysis demonstrated a significant decrease in height and lean mass standard deviation scores over the 12-month period, going against an expected trajectory over that time. In contrast, oestrogen suppression appeared not to affect the body composition of transboys; their measurements were not significantly different at baseline and after 12 months of treatment. The withdrawal of sex hormone secretion does not appear to have a significant impact on female post-pubertal body composition, in contrast to that seen at the menopause. This suggests that other factors may preserve normal body balance in adolescents in the absence of sex steroids.

Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People.

OBJECTIVE: The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study. RESEARCH DESIGN AND METHODS: Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated. RESULTS: In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01) increased. Fasting insulin (-1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (-1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (-1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (-0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] × min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] × min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (-2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (-0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (-1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] × min; P < 0.01), but fasting glucose (-0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] × min) remained unchanged. CONCLUSIONS: In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.

Adolescent development and psychosocial functioning after starting cross-sex hormones for gender dysphoria.

Purpose: To assess how adolescent development progresses and psychiatric symptoms develop among transsexual adolescents after starting cross-sex hormone treatment.Materials and methods: Retrospective chart review among 52 adolescents who came into gender identity assessment before age 18, were diagnosed with transsexualism and started hormonal gender reassignment. The subjects were followed over the so-called real-life phase of gender reassignment.Results: Those who did well in terms of psychiatric symptoms and functioning before cross-sex hormones mainly did well during real-life. Those who had psychiatric treatment needs or problems in school, peer relationships and managing everyday matters outside of home continued to have problems during real-life.Conclusion: Medical gender reassignment is not enough to improve functioning and relieve psychiatric comorbidities among adolescents with gender dysphoria. Appropriate interventions are warranted for psychiatric comorbidities and problems in adolescent development.

GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice.

INTRODUCTION: Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. METHODS: A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. RESULTS: National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. CONCLUSIONS: GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence.

Gender-Affirming Hormone Therapy, Vascular Health and Cardiovascular Disease in Transgender Adults.

Gender-affirming or cross-sex hormone therapy is integral to the management of transgender individuals yet our appreciation of the effects of such hormones on cardiovascular health is limited. Insights into vascular pathophysiology and outcomes in transgender people receiving sex steroids could be fundamental in providing better care for this population through the management of cardiovascular risk and more broadly advance our understanding of the role of sex and gender in vascular health and disease. In addition, there is a need to understand how gender-affirming hormone therapy impacts cardiovascular disease risk and events as transgender individuals age. This review explores the available evidence on the associations between gender-affirming hormones and cardiovascular events such as coronary artery disease, stroke, hypertension, thrombosis, lipid abnormalities, and diabetes mellitus. Current research about vascular outcomes in adults receiving hormonal therapy is limited by the absence of large cohort studies, lack of appropriate control populations, and inadequate data acquisition from gender identity services. Existing epidemiological data suggest that the use of estrogens in transgender females confers an increased risk of myocardial infarction and ischemic stroke. Conversely, transgender males receiving testosterone lack any consistent or convincing evidence of increased risk of cardiovascular or cerebrovascular disease. Further studies are required to confirm whether such risk exists and the mechanisms by which they occur.

Sex hormone intake in female blood donors: impact on haemolysis during cold storage and regulation of erythrocyte calcium influx by progesterone.

BACKGROUND: Sex hormone intake in blood donors may affect the quality of red blood cell (RBC) products via modulation of RBC function and predisposition to haemolysis during cold storage. The aims of this study were to evaluate the association between female sex hormone intake and RBC storage outcomes, and to examine possible mechanisms by which sex hormones interact with RBCs. MATERIALS AND METHODS: Sex hormone intake by race/ethnicity and menopausal status, and association analyses between hormone intake and donor scores of storage, osmotic or oxidative haemolysis, were evaluated in 6,636 female donors who participated in the National Heart, Lung and Blood Institute's RBC-Omics study. A calcium fluorophore, Fluo-3AM, was used to define RBC calcium influx in response to exogenous sex hormones or transient receptor potential cation (TRPC) channel drugs. RESULTS: Sex hormone intake was more prevalent in premenopausal women from all racial groups (18-31%) than in postmenopausal women (4-8%). Hormone intake was significantly (p<0.0001) associated with reduced storage haemolysis in all females, reduced osmotic haemolysis in postmenopausal donors (23.1±10.2% vs 26.8±12.0% in controls, p<0.001), and enhanced susceptibility to oxidative haemolysis in premenopausal women. In vitro, supraphysiological levels of progesterone (10 µmol/L), but not 17ß-oestradiol or testosterone, inhibited calcium influx into RBC and was associated with lower spontaneous haemolysis after 30 days of cold storage (0.95±0.18% vs 1.85±0.35% in controls, p<0.0001) or in response to a TRPC6 activator. CONCLUSIONS: Sex hormone intake in female donors is associated with changes in RBC predisposition to haemolysis. Menstrual status and the type of hormone preparation may contribute to differences in haemolytic responses of female RBCs to osmotic and oxidative stress. Progesterone modulates calcium influx into RBC via a mechanism that may involve interactions with membrane TRPC6 channels.