Gender-affirming Hormonal Therapy Research Articles

MON-196 Gender-Affirming Hormonal Therapy and Incidence of Metabolic Syndrome and Cardiovascular Events in Patients with Gender Dysphoria

Background: Long-term effects of gender-affirming hormonal therapy (GAHT) on cardiovascular risk factors and metabolic syndrome (MS) is currently unclear. Particularly, the effect of GAHT on cardiovascular outcomes in older individuals (>60 years) with gender dysphoria (GD) is unknown. The aim of this study was to examine the effect of GAHT on cardiovascular risk factors, MS and the incidence of T2DM in subjects with GD. Methods: We reviewed the records of 75 subjects with GD, 54 transwomen (age 49 ± 2 years) and 21 transmen (age 37 ± 2 years), who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol) of which 55 were followed for at least 1 year. MS was defined based on ATP III criteria. As a control group, we reviewed the records of 30 subjects without GD who attended the endocrinology clinic for other hormone-related disorders. Results: The median (IR) follow-up was 22 (11-39) months for transwomen and 15 (11-21) months for transmen. In transwomen plasma testosterone levels decreased (379 ± 31 vs 71 ± 18 ng/dL), estradiol increased (40 ± 7 vs 124 ± 34 pg/mL) while the plasma testosterone levels increased in transmen (57 ± 14 vs 411 ± 79 ng/dL). At baseline, 24% of transwomen had MS and after 1 year, 16% of subjects had MS. In transmen, the prevalence of MS was similar before and 1 year after treatment (25 % vs. 24%). In transwomen, GAHT was associated with mild weight gain, BMI increased (29 ± 1 vs. 30 ± 1 kg/m2, p=0.04). There was no difference in HDL, total cholesterol and triglyceride levels before and after hormone therapy, though LDL cholesterol tended to decrease (101 ± 6 vs. 90 ± 6 mg/dL, p=0.06). There was no change in HbA1C, FPG or SBP in transwomen, though DBP decreased (77 ± 1 vs. 74 ± 1 mmHg, p=0.05). In transmen, no changes were observed in BMI, HDL, total cholesterol, triglycerides, LDL, HbA1C, FPG and blood pressure. There were no new cases of T2DM, however 1 transman developed MS, 1 transman had CABG and 1 transwoman died from laryngeal cancer. There were no new cases of myocardial infarction or stroke in subjects with and without GD. For subjects above 60 years (n=16, 13 transwomen and 3 transmen), BMI in transwomen increased (27 ± 1 vs. 29 ± 2 kg/m2, p=0.03), there was no change in HDL, LDL and total cholesterol, triglycerides, HbA1C, FPG or blood pressure. In 3 transmen older than 60 years old, only the LDL decreased (194 ± 59 vs. 141 ± 55 mg/dL, p=0.006). In the entire group as well as older individuals with GD the incidence of CV events were not different from the control group. Conclusion: GAHT for 1.5 years was not associated with worsening cardiovascular risk factors, metabolic syndrome or incidence of T2DM in both transmen and transwomen regardless of their age. Long-term studies are required to assess the definite effects of GAHT on cardiovascular outcomes.

Cardiovascular disease in transgendered people: A review of the literature and discussion of risk.

This review examines the impact of gender affirming hormone therapy used in the transgendered and non-binary populations on cardiovascular outcomes and surrogate markers of cardiovascular health. Current evidence suggests that hormonal therapy for transgendered women decreases or is neutral regarding myocardial infarction risk. There is an increased incidence of venous thromboembolism (VTE), but newer studies suggest that the risk is significantly lower than previously described. For transgendered men, there appears to be an adverse effect on lipid parameters but this does not translate into an increased risk of cardiovascular disease above that of general male population. In all transgendered people, risk factor interventions such as smoking cessation, weight management and treatment of co-morbid conditions are important in optimising cardiovascular health. The effect of gender affirming hormonal therapy in transgendered people is difficult to interpret due to the variety of hormone regimens used, the relative brevity of the periods of observation and the influence of confounding factors such as the historical use of less physiological, oestrogens such as conjugated equine oestrogen and ethinylestradiol which are more pro-thrombotic than the 17β oestradiol that is used in modern practice.

Intracranial Hypertension in Transgender Patients

Idiopathic intracranial hypertension (IIH) is a potentially blinding condition characterized by increased intracranial pressure, papilledema, headaches, and vision loss (1). The role of exogenous sex hormones in the development of IIH is controversial (2). Five cases of IIH occurring in transgender patients undergoing female-to-male (FTM) transition with exogenous testosterone have been reported, suggestive of a causal relationship between exogenous testosterone use and IIH (3). In 3 of the 5 patients, exogenous testosterone was altered or discontinued. We report 2 additional cases in transgender patients: one in a patient undergoing FTM transition and the other in a patient undergoing male-to-female (MTF) transition. In both, the manifestations of intracranial hypertension were managed entirely without any modification of the patient's hormonal therapies, demonstrating that gender-affirming hormonal therapy can be safely continued in transgender patients with IIH. A 28-year-old obese (body mass index [BMI] 30.13 kg/m2) transgender woman was evaluated in our clinic for optic disc swelling. She had begun oral estradiol (Estrace) and spironolactone for MTF gender transition 1 year prior, and subsequently developed visual obscurations, frequent headaches, and pulsatile tinnitus. Eight months after starting hormone therapy, bilateral optic disc edema was detected and brain MRI and magnetic resonance venography (MRV) showed bilateral transverse sigmoid sinus narrowing. Two lumbar punctures (LP) revealed opening pressures of 30 cm H20 and 39 cm H20 with normal constituents. She was prescribed extended-release acetazolamide 500 mg twice daily, hormone therapy was discontinued, and she was referred to our clinic. On our examination, visual acuity was 20/15 in each eye without a relative afferent pupillary defect. There was bilateral optic disc edema. Automated visual fields (Humphrey 24-2) showed enlarged blind spots with a mean deviation of −1.36 dB, right eye, and −2.11 dB, left eye. On spectral domain optical coherence tomography (SD-OCT; Spectralis Tracking Laser Tomography; Heidelberg Engineering, Inc; Heidelberg, Germany), the retinal nerve fiber layer was thickened bilaterally, measuring 127 µm in each eye. Treatment with acetazolamide was continued. In consultation with the patient and her reproductive endocrinologist, estradiol therapy was resumed. Over the next 5 months, her headaches and papilledema resolved. Her estradiol was ultimately changed by her reproductive endocrinologist to a sublingual formulation to further increase her serum estrogen levels and suppress testosterone. She has remained in remission from IIH despite these changes to her hormonal therapy. A 31-year-old obese (BMI 56.5 kg/m2) transgender man was referred to our clinic for headaches and bilateral optic disc edema. He had previously been taking testosterone injections for FTM gender transition but had been off testosterone injections for 1 year before presentation. His visual acuity was 20/20 in both eyes, no afferent relative pupillary defect was detected, and Ishihara color plates demonstrated no deficits. Funduscopic examination revealed edematous optic discs while automated visual fields (Humphrey 24-2) revealed enlarged blind spots with a mean deviation of −3.80 dB, right eye, and −3.91 dB, left eye. With SD-OCT testing, peripapillary retinal nerve fiber thicknesses measured 385 µm, right eye, and 156 µm, left eye. MRI and MRV were unremarkable. LP revealed an opening pressure of 54 cm H2O with normal constituents. The patient was prescribed extended release acetazolamide 500 mg twice daily. He was then seen by his reproductive endocrinologist, resumed testosterone therapy, and sustained an intentional 20-pound weight loss. Over the ensuing 6 months, his papilledema resolved. There is no evidence-based consensus guiding the management of hormone therapy in transgender patients with IIH. Given the poorly understood, and possibly causative role of sex hormones in the development of IIH, clinicians may be inclined to alter gender-affirming hormone therapy once the diagnosis of IIH is made. Of the 5 previously reported cases of IIH developing in FTM patients receiving testosterone, the dose testosterone was reduced in 2 patients and changed to an alternate formulation in a third (3). Similarly, in our patient undergoing MTF transition, estradiol was stopped before our evaluation. Remission from IIH was achieved in both of our patients while continuing hormone therapy. In the patient undergoing MTF transition, hormone therapy was safely resumed and subsequently increased to suppress endogenous testosterone; she has remained in remission on acetazolamide. Likewise, in the patient undergoing FTM transition, IIH resolved with weight loss and acetazolamide, and he has remained in remission even after resumption of regular testosterone injections. Although it is uncertain if hormone therapy can precipitate IIH, we report 2 instances of IIH in transgender individuals that were successfully treated without alteration to the patient's gender-affirming hormone therapy. Patients with IIH undergoing hormone therapy for gender transition may still be responsive to conventional treatment without the need for change in hormone therapy.

Prospective Evaluation of Self-Reported Aggression in Transgender Persons

BackgroundAlthough research on the relation between testosterone and aggression in humans is inconclusive, guidelines (including the World Professional Association for Transgender Health Standards of Care, edition 7) have warned for an increase in aggression in transgender men taking testosterone treatment. AimsTo investigate the association between levels of testosterone and aggression in treatment-seeking transgender people and explore the role of mental health psychopathology (anxiety and depressive symptoms) and social support in aggression in this population. MethodsEvery transgender person invited for assessment at a national transgender health clinic in the United Kingdom during a 3-year period (2012–2015) completed self-report measures for interpersonal problems, including levels of aggression (Inventory of Interpersonal Problems [IIP-32]), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), social support (Multidimensional Scale of Perceived Social Support), and experiences of transphobia before and 1 year after the initiation of gender-affirming hormonal therapy. Correlations between prospective scores for the IIP-32 factor “too aggressive” and prospective levels of sex steroids, prospective psychological (HADS), and baseline psychosocial measurements were tested. OutcomesProspective scores for the factor “too aggressive” were not correlated to prospective serum testosterone levels. ResultsResults of 140 people (56 transgender men, 84 transgender women) were analyzed. A prospective increase in scores for the factor “too aggressive” of the IIP-32 in transgender men 1 year after being treated with testosterone treatment or a decrease of the IIP-32 aggression scores in transgender women 1 year after gender-affirming hormonal therapy was not found. However, a positive correlation was found between increasing HADS anxiety scores and increasing scores for the IIP-32 “too aggressive” score in the entire study population and a positive correlation with lower support from friends in transgender women. Clinical ImplicationsHormone-prescribing physicians can be reassured that the long-term administration of testosterone in transgender men does not increase aggressive behavior. Strengths and LimitationsThis is the 1st prospective study to assess the effect of gender-affirming hormonal care on aggression. Limitations included the use of different laboratories, the use of a patient-reported outcome measure, and the lack of aggression subtypes. ConclusionsTestosterone therapy was not associated with an increase in levels of aggression in transgender men or a decrease in aggressive behavior in transgender women on antiandrogen and estrogen therapy, but other psychological and/or social factors, such as anxiety levels, appear to contribute to self-reported aggression in transgender people.Defreyne J, T'Sjoen G, Bouman WP, et al. Prospective Evaluation of Self-Reported Aggression in Transgender Persons. J Sex Med 2018;15:768–776.