Effects Of Cross-sex Hormone Therapy Research Articles

Effects of Cross-Sex Hormone Therapy on Metabolic Parameters and Aortic Relaxation in Castrated Male Rats

With the rising awareness, the number of individuals identifying themselves as transgender in the US is increasing over the years. Cross-sex hormone therapy (CSHT) may alter numerous cardiometabolic parameters leading to the increased risk of cardiovascular diseases (CVD) in transgender population. Epidemiological studies suggest that transgender females (male to female, MtF) on estrogen therapy develop higher risk of CVD compared to transgender males (female to male, FtM) taking testosterone. Underlying mechanisms of impaired cardiovascular functions in MtF are not well documented. This study was undertaken to examine the effects of 17β-estradiol (E2) on certain cardiometabolic parameters and aortic reactivity in castrated (CAS) male Sprague Dawley (SD) rats. The 8-10-weeks old CAS rats were subcutaneously implanted with either 1.5 mg of E2 (CAS+E2) or placebo (CAS+PL) containing pellets for ~35 days. The age-matched SD intact male (IM) rats were also included in the experimental groups. After performing the glucose tolerance test, animals were sacrificed, and the blood was collected for later measurements of the HbA1C and triglyceride (TG) levels. Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh) in aortic rings pre-contracted with phenylephrine (PE) was measured before and after treatment with indomethacin (a cyclooxygenase inhibitor), followed by L-NAME [a nonselective nitric oxide (NO) synthase (NOS) inhibitor]. Contractile responses to PE before and after L-NAME in aortic rings and sodium nitroprusside (SNP)-induced relaxation responses in endothelium-denuded rings were also measured. Here, we report the decreased body weight and visceral white adipose tissue, and improved HbA1C and glucose tolerance in E2-treated CAS rats. However, the E2-treated CAS rats exhibited elevated plasma level of TG. Furthermore, the vascular relaxation to ACh was significantly impaired in aortas from this group compared to those in CAS+PL and IM rats. The impairment of ACh responses in CAS+E2 rats was accompanied by a significant decrease in NO contribution to ACh vasorelaxation. The basal NO levels and the smooth muscle sensitivity to NO were not altered, whereas the maximum contractile responses to PE were enhanced in aortas of CAS+E2 group compared to IM. In conclusion, our data suggests that the glucose homeostasis was improved in CAS+E2 rats. Regardless, this group exhibited increased level of TG in plasma and decreased aortic vasorelaxation to ACh. The impairment of EDV in E2-treated CAS rats might be due to reduced NO-mediated vasorelaxation or increased contractile responses observed in this group. Additional studies are needed to document the underlying mechanisms for improvement of glucose homeostasis and impairment of EDV in CAS+E2 rats. NIDA/NIGMS, 1SC1DA052120-01 to MF and Bridge Grant from University of the Pacific to RR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cross-sexual Effects of Testosterone on Mesenteric Arterial Reactivity in Ovariectomized Female Rats

The number of transgender individuals is on the rise in the United States. Although there are studies on the effects of sex hormones on cardiovascular function of cisgender male and female, still much is not known about the effects of cross-sex hormone therapy (CSHT) on cardiovascular function in transgender individuals. It has been shown that the risk factors of cardiovascular diseases (CVD) are increased in transgenders after they undergo CSHT. Epidemiological studies suggest that transgender females (male to female, MtF) on estrogen therapy develop higher risk of CVD compared to transgender males (female to male, FtM) taking testosterone. This study investigates the effects of testosterone or estrogen treatment on the third branch of mesenteric arterial reactivity in ovariectomized female rats. Briefly, 8-10 weeks old female Sprague Dawley (SD) rats were ovariectomized (OVX) and subcutaneously implanted with placebo (OVX + PL) or testosterone (OVX + T, 7.5 mg) or 17β- estradiol (OVX + E2, 1.5 mg) pellets for about 35 days. Age matched intact female SD rats were also included in the experimental groups. Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh) was measured in the precontracted mesenteric arteries with phenylephrine (PE), using wire myography. Responses to sodium nitroprusside (SNP)-induced vasorelaxation, and PE- and endothelin-1 (ET-1) induced vasocontraction were also determined. We demonstrated that the responses to ACh in rat mesenteric arteries were not altered by either ovariectomy or estrogen treatment. However, testosterone treatment of OVX female rats significantly enhanced the sensitivity to ACh-induced vasorelaxation compared with those in other experimental groups. Moreover, the mesenteric arteries of OVX + T exhibited a trend of reduced sensitivity to PE responses compared to other groups. Furthermore, the maximum tension to ET-1 was significantly reduced in mesenteric arteries of OVX + T compared to OVX+E2 and OVX+PL groups. The vasorelaxation responses to SNP were not altered in any of experimental groups studied. These data suggest that elevated sensitivity to ACh in testosterone-treated ovariectomized female rats might be, in part, due to reduced vessel responses to contractile agents, but not altered sensitivity of smooth muscle to nitric oxide (NO) in this group. Additional studies are needed to investigate the underlying mechanisms and document the consequences for the improvement of EDV observed in OVX + T rats. NIDA/NIGMS, 1SC1DA052120-01 to MF, Bridge Grant from University of the Pacific to RR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lipidni status transrodnih osoba koje su na terapiji gonadnim hormonima suprotnog pola šest meseci

Introduction: The term "transgender" refers to a person whose sex assigned at birth does not match their gender identity. Transsexualism can be diagnosed in all ages, although the first signs can be seen in early childhood. This condition is treated with cross-sex hormone therapy (CSHT) and surgical reconstructions with the goal of matching the physical sex with the one that the person identifies with. Aim: To study the effects of cross-sex hormone therapy with testosterone on anthropometric characteristics, lipid and hormone status in trans men (female to male (FtM) transgenders). Material and methods: The study includes 31 FtM patients with a gender identity disorder. The beginning of CSHT was at age 26.03 ± 5.21. Patients were treated at the Clinic of Endocrinology, diabetes and metabolic diseases, University Clinical Center of Serbia. Lipid and hormone status before and during therapy were analyzed. Results: The BMI has increased significantly. Mean levels of HDL and Lp(a) were decreased significantly, and there was a significant decrease in ApoA1. There were no changes in other lipid levels. During six months of testosterone therapy levels of FSH, LH and estradiol showed a significant decrease, while testosterone has increased significantly. Higher values of RBC and hemoglobin were found. Conclusion: CSHT with testosterone do not lead to pathological alteration of lipid profile if dosed properly.

Estradiol Replacement as a Potential Enhancer of Working Memory and Neuroplasticity in Hypogonadal Trans Women

Introduction: The cognitive effects of cross-sex hormone therapy (CSHT) are not well understood. In cisgender individuals, sex hormone therapy can impact neurotransmitter levels and structural anatomy. Similarly, in gender-diverse persons, CSHT has been associated with neural adaptations, such as growth in brain structures resembling those observed in cisgender individuals of the same sex. Hormone-related changes in learning and memory, as seen in menopause, are associated with physiological hypogonadism or a decline in hormones, such as estradiol. The present study examined the effect of estradiol administration in humans on glutamate concentration in brain regions involved in semantic and working memory (i.e., the dorsolateral prefrontal cortex [DLPFC], the posterior hippocampus, and the pregenual anterior cingulate cortex) and its relationship with memory. Methods: Eighteen trans women (male biological sex assigned at birth) ceased CSHT for 30 days for a washout phase (t1) upon study enrollment to reach a hypogonadal state. Working and semantic memory, cognition, hormonal assays, and brain imaging were assessed. Participants resumed CSHT for 60 days for a replacement phase (t2), after which the same evaluations from t1 were repeated. Results: Estradiol increased among trans women after 60 days of resumed CSHT with significant improvements in semantic memory compared to the hypogonadal phase. Working memory recall was significantly and positively correlated to glutamate in the DLPFC during the reinstatement phase, although the relationship was not moderated by levels of estradiol. Discussion: These results may have clinical implications for the therapeutic effects of estradiol replacement, serving as a protective factor against cognitive decline and impairment for trans women post-gonadectomy.

Aortic Relaxation in Castrated Male Rats and Responses to Estrogen Treatment

Previous studies suggest that risk factors for cardiovascular diseases (CVD) have increased in the transgender population after they undergo cross‐sex hormone therapy (CSHT). Several studies, including ours in animal models as well as in humans, have shown that estrogen exerts direct beneficial effects on the vessel wall in healthy females. A growing body of evidence also suggests that androgen exhibits protective actions on the cardiovascular system. However, the effects of CSHT in cardiovascular physiology in males or females are less understood.The current study was, therefore, undertaken to evaluate the effects of estrogen treatment on aortic reactivity in castrated (CAS) male rats. Specifically, we investigated the effects of in vivo treatment with 17β‐estradiol (E2) on the aortic responses of CAS male as well as ovariectomized (OVX) female rats.Age‐matched CAS male and OVX female rats were implanted subcutaneously with either 17β‐estradiol (E2,1.5 mg) or a placebo‐containing pellet for 30 days. Endothelium‐dependent vasorelaxation (EDV) in response to acetylcholine (ACh, 10‐8 to 10‐5 M) in aorta precontracted with phenylephrine (PE, 2 µM) was measured before and after pretreatment with indomethacin (10 µM, cyclooxygenase inhibitor), followed by N‐nitro‐ L‐arginine methyl ester [L‐NAME, 200 µM, a nonselective nitric oxide synthase (NOS) inhibitor]. Endothelium‐independent vasorelaxation was assessed by measuring sodium nitroprusside (SNP)‐induced relaxation response in endothelium‐denuded rings in addition to the contractile response curves to PE before and after pretreatment with L‐NAME in aortic rings.EDV to ACh was significantly impaired in aortic rings from E2‐treated CAS rats compared to their placebo‐treated counterparts and E2‐treated OVX rats. The impairment of EDV to ACh in E2‐treated CAS rats was accompanied by a significant decrease in nitric oxide (NO) contribution to ACh‐induced relaxation in this group. The smooth muscle sensitivity to NO as measured by SNP relaxation response curve was not altered, whereas the responsiveness to PE was slightly enhanced in the aortas of E2‐treated CAS group compared to those in other experimental groups. Endothelium‐derived NO release during smooth muscle contraction, as assessed by the potentiation of the response to PE after NOS inhibition, was not different in the aortas of experimental groups.Overall, our data demonstrate that aortic function was altered in E2‐treated CAS male rats. Here, we provide the first evidence of impairment in aortic relaxation in E2‐treated CAS male rats, possibly via a significant decrease in the relative contribution of NO to the regulation of vascular relaxation response. Furthermore, the comparison of current data in the CAS male rats with our recently published data on the aortic reactivity in the intact males appears to rule out any effect of testosterone deprivation on the stimulated release of NO in male rat aortas. Additional studies will be needed to document the direction and magnitude of CSHT interaction with vasculatures.

An Examination of the Sex-Specific Nature of Nutrition Assessment within the Nutrition Care Process: Considerations for Nutrition and Dietetics Practitioners Working with Transgender and Gender Diverse Clients

An Examination of the Sex-Specific Nature of Nutrition Assessment within the Nutrition Care Process: Considerations for Nutrition and Dietetics Practitioners Working with Transgender and Gender Diverse Clients

SPORTS AND PERFORMANCE IN THE TRANSGENDER POPULATION: A SYSTEMATIC REVIEW AND META-ANALYSIS

ABSTRACT Introduction: The debate surrounding the regulations on the participation of transgender individuals in sports is not recent, but it is still ongoing. Some sports organizations are more flexible in this regard, while others are more conservative. Objective: Through a systematic review and meta-analysis, this study summarizes the scientific evidence of the effects of cross-sex hormone therapy on muscle strength, hematocrit, and hemoglobin measurements, parameters that seem to be linked to sports performance. Methods: We conducted electronic searches for manuscripts published before November 20th, 2020. Studies published in three different databases (PubMed, SciELO, and Lilacs) were included, without any time or language restriction, and using keywords such as “transgender”, “gender dysphoria”, “strength”, “hematocrit”, and “hemoglobin”. The PRISMA systematization was used for the elaboration of this review, while a meta-analysis was conducted to mathematically evidence the results. The meta-analysis was performed using the random effect model, to find the pooled estimate effect of cross-sex hormone therapy on the parameters analyzed. Results: The electronic search retrieved 21 articles that were eligible for inclusion. Cross-sex hormone therapy influenced the three parameters analyzed in almost all the studies. Overall, there was a significant increase in muscle strength in female-to-males (FtMs), per muscle group analyzed: +17.7% (95% confidence interval [CI]14.9;20.6). In male-to-females (MtFs) the results of the muscle strength analysis were more controversial, but the pooled estimate effect showed a decrease: −3.6% (95% confidence interval [CI] −6.6; −0.6). Conclusion: Muscle strength, hematocrit, and hemoglobin were altered as a result of cross-sex hormone therapy in both FtMs and MtFs. However, there was a lack of studies comparing the transgender individuals to the population of the same desired gender. Such studies are needed, to better infer rules for the participation of transgender athletes in Olympic sports. Level of Evidence I; Systematic Review and Meta-analysis.

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

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. 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. 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. This observational, retrospective study revealed that gender-affirming HT increased the relative cardiovascular risk in trans masculine individuals.

SUN-052 Effects of Cross-Sex Hormone Therapy on Lipid Metabolism in Transgender Women and Men

Sex hormone therapy in cisgender persons (i.e. postmenopausal women and hypogonadal men and women) leads to changes in lipid metabolism and weight, but it is unclear to what extent this occurs in transgender persons receiving higher doses of cross-sex hormone therapy (CSHT) for the purpose of gender transition.Objective: To determine changes in lipid metabolism among transgender women (TW) and transgender men (TM) on CSHT.Methods: We conducted a retrospective chart review of patients identified at a transgender-specific clinic within an academic medical center. Data were collected on age, ethnicity, hormone therapies, lipid lowering therapy (LLT), surgical status, lipid panel, A1C, LFTs, BMI, and weight before and after initiation of HT. Patients on stable LLT were included but those with LLT initiated after baseline observation were excluded. Changes from baseline to post CSHT in TW and TM groups were evaluated with paired t-tests.Results: We identified 18 TW and 22 TM for whom laboratory data were available. Mean±SD age of TW was 33±13 years and for TM was 28±12 years; the majority (78%) were Caucasian. Mean±SD duration of HT in TW was 10.1±4.5 months and in TM 6.7±4.4 months. No patients had undergone gonadectomy at any time prior to or during the data collection period. One TW and one TM were on stable LLT during the observation period. All TW were treated with estradiol (78% oral, 11% patch) and spironolactone. In TW, there was a significant 10% increase in HDL from 48±17 mg/dl to 53±15 mg/dl (p=0.02) but there were no significant changes in other lipid fractions, A1c, or weight/BMI. The majority of TM (82%) were treated with weekly intramuscular testosterone-esters injections and the remainder with daily testosterone gel. More substantial and unfavorable metabolic changes occurred in the TM with a 15% decrease in HDL from 55±15 mg/dl to 47±10 mg/dl (p=0.004), increase in A1c from 5.07±0.45% to 5.22 ± 0.39%(p=0.04), increase in BMI from 29±10 kg/m2 to 31±10 kg/m2 (p=0.002), and a trend toward increased triglycerides (96±64 mg/dl to 110±80 mg/dl, p=0.07). Hemoglobin and hematocrit significantly increased in TM but there was no significant change in LFT in either group. Limitations include lack of data on body composition to determine relative changes in adipose tissue or muscle mass in relation to weight changes and small sample size.Conclusion: Our study suggests that CSHT has a neutral to slightly favorable impact on lipid metabolism in TW and a negative impact on lipids and glucose in TM. Larger, prospective studies are needed to determine whether these changes persist over the longer duration of CSHT and whether this translates to an increased risk of cardiovascular disease and mortality. Clinicians should inform TM patients about these potential negative effects of CSHT on lipid metabolism so that their patients can adopt healthy lifestyle interventions early on to optimize their cardiovascular risk.

Effect of Cross-Sex Hormone Therapy on Venous Thromboembolism Risk in Male-to-Female Gender-Affirming Surgery.

Individuals with gender dysphoria often seek medical interventions, such as hormone treatment and surgery, to live as their identified gender. Cross-sex hormone therapy typically consists of various estrogen formulations which confer varying risks of venous thromboembolism (VTE). Currently, there is no standard practice by surgeons regarding the preoperative gender-affirming surgery (GAS) hormone regimen of male-to-female (MTF) patients to minimize thromboembolic postoperative complications. The aim of this review is to examine the current literature on VTE occurring in MTF transgender patients on cross-sex hormone therapy (CSHT) when undergoing various gender-affirming surgeries-facial feminization surgery (FFS), top surgery (TS), and bottom surgery (BS)-to understand how evidence-based recommendations regarding perioperative hormone regimens can be established to improve clinical outcomes. Within the past 25 years, 7 published studies have examined the incidence of VTE in MTF patients undergoing GAS procedures. Two of these articles examined MTF patients undergoing FFS, 1 article reported a patient who had undergone BS and FFS during the same hospitalization, and the remaining 4 articles investigated VTE risk in BS. Our review supports that plastic surgeons who perform GAS are divided on their preferred CSHT protocols, with some requiring patients to suspend their CSHT weeks before surgery and others allowing patients to continue CSHT through the day of surgery. Three of the 7 studies detailed a CSHT perioperative regimen which instructed patients to suspend CSHT sometime before surgery; 1 study tapered CSHT to lower levels before surgery; the remaining 3 studies did not specify a CSHT perioperative regimen. This review highlights the paucity of data failing to support that continuing CSHT through GAS elevates VTE risk. We conclude that in the absence of definitive VTE risk factors (e.g., smoking, clotting disorders, or malignancy), surgeons may engage MTF patients in joint decision-making process to determine the most optimal perioperative CSHT management plan on a case-by-case basis. Future studies are warranted to evaluate VTE risk based on patient age, type of surgery, operating time, prophylactic measures, follow-up time, and CSHT perioperative regimens.

SUN-534 Effect of Cross-Sex Hormone Therapy on Body Composition, Visceral Adipose Tissue, and Bone Mineral Density in Transgender Men

In transgender men (FtM), testosterone therapy may induce changes in different body compartments. The aim of this study was to evaluate body fat and muscle mass, visceral adipose tissue and bone mineral density in FtM transgender individuals receiving cross-sex hormone therapy (CSHT). Sixty two FtM were included in the protocol and performed laboratory tests and dual energy X-ray absorptiometry (DXA) after 3 months of standard CSHT. The median age was 27.0 (21.5-35) years, BMI 25.8 (23.3-32.2) kg/m², and 53% of them had previously used testosterone therapy. Transgender men were compared with 23 natal men controls. Testosterone median levels were 2.03 ng/dl (0.29—5.12) and 4.75 ng/dl (3.47-5.48) in FtM and control individuals, respectively. Estradiol and SHBG were 52.8 pg/ml (30.0-96.2) and 25.2 nmol/l (19.4-49.1) in FtM, and 19.8 pg/ml (14.8-29.1) and 27.9 nmol/l (22.0-37.6) in controls. Transgender men were similar to male controls regarding age (p=0.149), weight (p=0.672), BMI (p=0.189), total fat mass (p=0.461), android / gynoid fat ratio (p=0.674), visceral adipose tissue (p=0.311), total lean mass (p=0.065) and L1L4, femoral neck and total hip BMD. Lean mass index (FNIH) was significantly lower in the FtM individuals [0.724 (0.623-0.825) vs. 0.923 (0.609-1.112), p=0.002]. A positive correlation was observed between testosterone levels and total lean mass (r=0.266, p=0.040) and FNIH index (r=0.378, p=0.003), while a negative correlation was found between SHBG levels and total lean mass (r= -0.348, p=0.008), android / gynoid fat ratio (r= -0.426, p=0.001) and visceral adipose tissue (r= -0.363, p=0.008). A subgroup of 23 FtM performed a second densitometry after a mean of 25.3±8.8 months, with the same equipment. No changes were observed regarding testosterone, SHBG and estradiol levels during this period. Significant Increase in the android / gynoid fat ratio [0.44 (0.32-0.52) vs. 0.48 (0.34-0.54); p=0.017] and decrease of the gynoid fat [43.4±8.3% vs 41.3±8.8%, p=0.05) were observed after CSHT. BMD remained stable along the time. Visceral adipose tissue varied from 522cm³ (117-988) to 612cm³ (271-1.172, p=0.054) after CSHT. In conclusion, preliminary results from this pilot study suggest that lean and fat mass parameters in FtM under CSHT are similar to natal men controls and that testosterone therapy is effective, but might increase abdominal and visceral fat in transgender men. Further studies with larger sample size are needed in order to confirm these findings.

159 Effects of Cross-sex Hormone Therapy on Laboratory Values in Female-to-male Transgender Patients

Cross-sex hormone therapy is increasingly accepted as essential to the wellbeing of transgender individuals. Cross-sex hormones have been shown to alter clinical laboratory values, but separate reference ranges have not been established for transgender patients due to a lack of knowledge and data on this population. Healthcare providers often rely on the results of laboratory tests to make diagnoses and treatment plans, and it is imperative that they do not misinterpret these results in transgender patients. The goal of this study is to investigate how changes in laboratory values in female-to-male (FTM) transgender patients are related to duration of testosterone treatment. We conducted a retrospective chart review of FTM patients attending transgender-specific clinics at an urban county hospital (Parkland, Dallas, TX) and a community clinic (Dallas Resource Center). Patients were included if they were biologic females taking testosterone, between the ages of 18 and 80, and had laboratory test results from at least one month after initiation of testosterone treatment. Each patient's complete blood count, metabolic panel, liver function tests, lipid panel, and hormone levels were recorded with a median follow-up time of 12 months.

Changes in hormonal and metabolic parameters in transgender subjects on cross-sex hormone therapy: A cohort study

ObjectivesGender identity disorder is defined as a strong and persistent cross-gender identification that is associated with a remarkable uneasiness of living in an incongruent gender (gender dysphoria). We performed a retrospective study on the hormonal and metabolic effects of cross-sex hormone therapy (CSHT) in a small cohort of transgender patients. Study designRetrospective study. Mean outcome measuresHormonal and biochemical parameters at baseline (i.e. before commencement of CSHT) and while on CSHT in 32 patients (21 male to female [MtF], 11 female to male [FtM]) referred to our Endocrinology Unit for gender dysphoria between January 2012 and February 2017. ResultsCompared with baseline, in MtF patients systolic blood pressure, red cell count, hemoglobin, hematocrit and total testosterone decreased significantly, while 17-β estradiol and SHBG increased significantly and trendwise significantly, respectively. In FtM patients, total testosterone, red cell count, hemoglobin, hematocrit, creatinine, ɣ-glutamyl transferase and alkaline phosphatase increased significantly, while fasting plasma glucose decreased trendwise significantly. In MtF patients 17-β estradiol correlated positively with SHBG and alkaline phosphatase and negatively with total cholesterol and HDL-c, whereas total testosterone correlated positively with systolic blood pressure, red cell count and hematocrit, and negatively with SHBG. In FtM patients total testosterone correlated positively with creatinine and alkaline phosphatase, while 17-β estradiol correlated positively with HDL-c. ConclusionsOur data are partly in line with other studies concerning the impact of CSHT on hormonal and metabolic parameters in transgender people. Metabolic changes appear, overall, to be modest, confirming the safety of CSHT.

Brain sexual differentiation and effects of cross-sex hormone therapy in transpeople: A resting-state functional magnetic resonance study

It is hypothesized that transpeople show sex-atypical differentiation of the brain. Various structural neuroimaging studies provide support for this notion, but little is known about the sexual differentiation of functional resting-state networks in transpeople. In this study we therefore aimed to determine whether brain functional connectivity (FC) patterns in transpeople are sex-typical or sex-atypical, before and after the start of cross-sex hormone therapy (CHT). We acquired resting-state functional magnetic resonance data in 36 transpeople (22 with female sex assigned at birth), first during gonadal suppression, and again four months after start of CHT, and in 37 cisgender people (20 females), both sessions without any hormonal intervention. We used independent component analysis to identify the default mode network (DMN), salience network (SN), and left and right working memory network (WMN). These spatial maps were used for group comparisons. Within the DMN, SN, and left WMN similar FC patterns were found across groups. However, within the right WMN, cisgender males showed significantly greater FC in the right caudate nucleus than cisgender females. There was no such sex difference in FC among the transgender groups and they did not differ significantly from either of the cisgender groups. CHT (in transgender participants) and circulating sex steroids (in cisgender participants) did not affect FC. Our findings may suggest that cisgender males and females experience a dissimilar (early) differentiation of the right WMN and that such differentiation is less pronounced in transpeople.

P.1.e.023 Functional mutations in CADPS identified in patients with early-onset bipolar disorder

Men and postmenopausal women exhibit a higher risk for atherosclerosis than premenopausal women. These differences were often attributed to sex steroids, but the role of estrogen and testosterone in atherosclerosis are more complex than anticipated. Cross-sex hormone therapy of transsexuals is an interesting model, which has been used to study hormonal effects on serum lipid profile, insulin resistance, and body composition. However, studies on macrophage cholesterol efflux, the first step in reverse cholesterol transport, are not available.The aim of this study was to evaluate the effect of cross-sex hormone therapy in transsexuals on the capacity of serum to accept cholesterol from macrophages.Cholesterol acceptor capacity (CAC) of serum from transsexuals before and after at least 6 months of hormone treatment was measured using macrophage tissue culture models.CAC of serum using the human acute monocytic leukemia cell line (THP-1 cells).Unexpectedly, the CAC of serum from male to female (MtF) transsexuals was not increased, but decreased after hormone therapy. Serum from female to male (FtM) transsexuals showed no changes in CAC.Despite drastic changes in hormone status, no increase in CAC was detected in MtF patients, and no alteration in CAC was seen in FtM patients. These data further challenge the traditional view that estrogen and testosterone exert beneficial and detrimental effects, respectively, on lipoprotein metabolism and ultimately atherosclerosis. Wultsch A, Kaufmann U, Ott J, Stojakovic T, Scharnagl H, Stangl H, and Strobl WM. Profound changes in sex hormone levels during cross-sex hormone therapy of transsexuals do not alter serum cholesterol acceptor capacity. J Sex Med 2015;12:1436–1439.

Profound Changes in Sex Hormone Levels during Cross-Sex Hormone Therapy of Transsexuals do not Alter Serum Cholesterol Acceptor Capacity

Men and postmenopausal women exhibit a higher risk for atherosclerosis than premenopausal women. These differences were often attributed to sex steroids, but the role of estrogen and testosterone in atherosclerosis are more complex than anticipated. Cross-sex hormone therapy of transsexuals is an interesting model, which has been used to study hormonal effects on serum lipid profile, insulin resistance, and body composition. However, studies on macrophage cholesterol efflux, the first step in reverse cholesterol transport, are not available. The aim of this study was to evaluate the effect of cross-sex hormone therapy in transsexuals on the capacity of serum to accept cholesterol from macrophages. Cholesterol acceptor capacity (CAC) of serum from transsexuals before and after at least 6 months of hormone treatment was measured using macrophage tissue culture models. CAC of serum using the human acute monocytic leukemia cell line (THP-1 cells). Unexpectedly, the CAC of serum from male to female (MtF) transsexuals was not increased, but decreased after hormone therapy. Serum from female to male (FtM) transsexuals showed no changes in CAC. Despite drastic changes in hormone status, no increase in CAC was detected in MtF patients, and no alteration in CAC was seen in FtM patients. These data further challenge the traditional view that estrogen and testosterone exert beneficial and detrimental effects, respectively, on lipoprotein metabolism and ultimately atherosclerosis.

The effects of cross-sex hormone therapy on body weight and fat percentage in transgender individuals

The effects of cross-sex hormone therapy on body weight and fat percentage in transgender individuals

Clinical Review: Breast Development in Trans Women Receiving Cross-Sex Hormones

In trans women (male-to-female transsexual persons), cross-sex hormone therapy is administered to induce feminization. Breast development is an important part of feminization for most trans women. The aim of this study is to assess the effect of cross-sex hormone therapy on breast development in adult trans women. Additionally, we aimed to investigate the benefit or harm of administration of progestogens on breast development. A review of the literature in Embase, Medline, The Cochrane Library, PsycINFO databases, PubMed, and Web of Knowledge until January 2014. Effects of cross-sex hormone therapy and progestogens on breast development in trans women. Only few studies with low quality of evidence addressed these topics. The available evidence suggests that breast development is insufficient for the majority of trans women and that type and dosage of hormonal therapy seem not to have an important role on final breast size. Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in trans women is extremely sparse and based on low quality of evidence. Current evidence does not provide evidence that progestogens enhance breast development in trans women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions.

Sexual Desire in Trans Persons: Associations with Sex Reassignment Treatment

Sex steroids and genital surgery are known to affect sexual desire, but little research has focused on the effects of cross-sex hormone therapy and sex reassignment surgery on sexual desire in trans persons. This study aims to explore associations between sex reassignment therapy (SRT) and sexual desire in a large cohort of trans persons. A cross-sectional single specialized center study including 214 trans women (male-to-female trans persons) and 138 trans men (female-to-male trans persons). Questionnaires assessing demographics, medical history, frequency of sexual desire, hypoactive sexual desire disorder (HSDD), and treatment satisfaction. In retrospect, 62.4% of trans women reported a decrease in sexual desire after SRT. Seventy-three percent of trans women never or rarely experienced spontaneous and responsive sexual desire. A third reported associated personal or relational distress resulting in a prevalence of HSDD of 22%. Respondents who had undergone vaginoplasty experienced more spontaneous sexual desire compared with those who planned this surgery but had not yet undergone it (P = 0.03). In retrospect, the majority of trans men (71.0%) reported an increase in sexual desire after SRT. Thirty percent of trans men never or rarely felt sexual desire; 39.7% from time to time, and 30.6% often or always. Five percent of trans men met the criteria for HSDD. Trans men who were less satisfied with the phalloplasty had a higher prevalence of HSDD (P = 0.02). Trans persons who were more satisfied with the hormonal therapy had a lower prevalence of HSDD (P = 0.02). HSDD was more prevalent in trans women compared with trans men. The majority of trans women reported a decrease in sexual desire after SRT, whereas the opposite was observed in trans men. Our results show a significant sexual impact of surgical interventions and both hormonal and surgical treatment satisfaction on the sexual desire in trans persons.

Long‐Term Evaluation of Cross‐Sex Hormone Treatment in Transsexual Persons

Long-term effects and side effects of cross-sex hormone treatment in transsexual persons are not well known. The aim of this study is to describe the effects and side effects of cross-sex hormone therapy in both transsexual men and women. Hormone levels were measured by immunoassays. Physical health was assessed by physical examination and questionnaires on general health and specific side effects, areal bone parameters by dual energy X-ray absorptiometry. Single center cross-sectional study in 100 transsexual persons post-sex reassignment surgery and on average 10 years on cross-sex hormone therapy. Transsexual men did not experience important side effects such as cardiovascular events, hormone-related cancers, or osteoporosis. In contrast, a quarter of the transsexual women had osteoporosis at the lumbar spine and radius. Moreover, 6% of transsexual women experienced a thromboembolic event and another 6% experienced other cardiovascular problems after on average 11.3 hormone treatment years. None of the transsexual women experienced a hormone-related cancer during treatment. Cross-sex hormone treatment appears to be safe in transsexual men. On the other hand, a substantial number of transsexual women suffered from osteoporosis at the lumbar spine and distal arm. Twelve percent of transsexual women experienced thromboembolic and/or other cardiovascular events during hormone treatment, possibly related to older age, estrogen treatment, and lifestyle factors. In order to decrease cardiovascular morbidity, more attention should be paid to decrease cardiovascular risk factors during hormone therapy management.