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Papers by Alessandra Fisher

Endocrine Abstracts, 2018

Journal of Clinical Medicine, 2022

Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgende... more Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgender people is limited. For this reason, in 2010 the European Network for the Investigation of Gender Incongruence (ENIGI) study was born. The aim of this review is to summarize evidence emerging from this prospective multicentric study and to identify future perspectives. GAHT was effective in inducing desired body changes in both trans AMAB and AFAB people (assigned male and female at birth, respectively). Evidence from the ENIGI study confirmed the overall safety of GAHT in the short/mid-term. In trans AMAB people, an increase in prolactin levels was demonstrated, whereas the most common side effects in trans AFAB people were acne development, erythrocytosis, and unfavorable changes in lipid profile. The main future perspectives should include the evaluation of the efficacy and safety of non-standardized hormonal treatment in non-binary trans people. Furthermore, long-term safety data on...

The Journal of Sexual Medicine, 2021

BACKGROUND Over the last few years, the gender binary has been questioned, highlighting the exist... more BACKGROUND Over the last few years, the gender binary has been questioned, highlighting the existence of gender diverse people, who identify as neither (exclusively) male nor female. AIM The present study evaluated the possible differences in terms of psychological wellbeing between binary and gender diverse individuals, as well as the role of perceived social acceptance and religious fundamentalism as possible mediators of psychopathology in gender diverse people. Furthermore, the diversity of gender-affirming hormonal treatment requests according to gender identification was investigated. METHODS A sample of 563 transgender people aged 18-70 was enrolled (n = 264 assigned female at birth, AFAB and n = 299 assigned male at birth, AMAB), all individuals referring to several Italian gender clinics. A subdivision of the study population based on the gender identity visual analog scale (GI-VAS) median was performed, in order to distinguish between gender diverse and binary transgender individuals. Moreover, a linear regression analysis was performed entering logarithmically transformed GI-VAS (Log GI-VAS) into the models with psychometric scales. OUTCOMES Psychometric and sociodemographic data, as well as information regarding requests for gender-affirming treatments, were extrapolated from the clinical interviews conducted during the first referral. RESULTS Gender diverse individuals showed significantly less intense gender dysphoria and higher levels of depression and anxiety compared to binary ones; accordingly, a less binary gender identity correlated with higher levels of depression and anxiety and lower levels of gender dysphoria. The depressive symptomatology in gender diverse people was partially mediated by perceived discrimination and humiliation. Moreover, gender diverse AMAB people sought a non-standard hormonal treatment more often than their binary counterpart. CLINICAL IMPLICATIONS The present study highlights the importance for transgender health professionals, when planning gender-affirming hormonal treatments, to offer flexible interventions, tailored on the patient's needs and goals. STRENGTHS & LIMITATIONS Strengths included exploring whether and how perceived discrimination may affect mental health in gender diverse people. Limitations included the enrolled sample of people referring to different gender clinics, which is not fully representative of the transgender population. CONCLUSION This study highlights the importance of evaluating each individual's unique health care needs, exploring each single request and its underlying reasons. Romani A., Mazzoli F., Ristori J., et al. Psychological Wellbeing and Perceived Social Acceptance in Gender Diverse Individuals. J Sex Med 2021;18:1933-1944.

The Journal of Clinical Endocrinology & Metabolism, 2021

Context Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts ... more Context Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent. Objective To assess the lowest effective dose of CPA in trans women to prevent side effects. Methods This longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n = 882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of...

The Journal of Sexual Medicine, 2021

BACKGROUND Cardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAH... more BACKGROUND Cardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAHT) in transgender individuals still remain largely unknown. AIM To evaluate changes in the 30-year Framingham cardiovascular disease (CVD) risk in a large cohort of transgender individuals after the start of GAHT. METHODS In a multicenter prospective study, a consecutive series of 309 participants (165 transmen and 144 transwomen) was evaluated during a 2-year follow-up. Prospectively, after the start of GAHT a physical examination was performed and blood samples were drawn. CVD risk was calculated for each person, according to the Framingham 30-year CVD risk estimate. MAIN OUTCOME MEASURE Changes in CV risk factors and 30-year Framingham CVD risk during GAHT. CLINICAL IMPLICATIONS In transmen testosterone-induced lipid profile alterations may have a clinical relevance on the individual long-term CVD risk. STRENGTHS & LIMITATIONS The strength of the present study is the possibility to predict long-term CV outcomes in transgender individuals receiving GAHT based on a short observation; whereas the main limitation is that CVD risk prospective changes mainly represent the expression of risk factors changes during GAHT. RESULTS In transwomen a significant decrease in triglycerides, total cholesterol and LDL-cholesterol was observed during the 2-year follow-up (P < .05), whereas unfavorable lipid changes - such as increased total cholesterol, triglycerides, and LDL cholesterol levels and decreased HDL cholesterol levels (P < .05)- occurred after the start of GAHT in transmen. These changes in risk factors led to an increase in the risk of general and hard CVD events based on lipid profile over time in transmen (P = .001 and P = .005, respectively). No significant changes in general and hard CVD risk based on lipid profile were observed in transwomen over time. CONCLUSIONS Our findings confirmed the unfavorable lipid changes in transmen after the start of GAHT even during a longer follow-up, empathizing the potential clinical impact of these modifications on individual long-term CVD risk. Cocchetti C, Castellini G, Iacuaniello D, et al. Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI). J Sex Med 2021;xxx:xxx-xxx.

The Journal of Clinical Endocrinology & Metabolism, 2021

Introduction Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease... more Introduction Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease and is influenced by sex hormones. Our aim was to investigate changes in visceral fat and the ratio of visceral fat to total body fat (VAT/TBF) and their associations with changes in lipids and insulin resistance after 1 year of hormone therapy in trans persons. Methods In 179 trans women and 162 trans men, changes in total body and visceral fat estimated with dual-energy X-ray absorptiometry before and after 1 year of hormone therapy were related to lipids and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] with linear regression analysis. Results In trans women, total body fat increased by 4.0 kg (95% CI 3.4, 4.7), while the amount of visceral fat did not change (−2 grams; 95% CI −15, 11), albeit with a large range from −318 to 281, resulting in a decrease in the VAT/TBF ratio of 17% (95% CI 15, 19). In trans men, total body fat decreased with 2.8 kg ...

Journal of Clinical Medicine, 2021

Improving transgender people’s quality of life (QoL) is the most important goal of gender-affirmi... more Improving transgender people’s quality of life (QoL) is the most important goal of gender-affirming care. Prospective changes in affect can influence QoL. We aim to assess the impact of initiating gender-affirming hormonal treatment (HT) on affect. In the European Network for the Investigation of Gender Incongruence (ENIGI) study, we prospectively collected data of 873 participants (451 transwomen (TW) and 422 transmen (TM)). At baseline, psychological questionnaires including the Positive and Negative Affect Schedule (PANAS) were administered. The PANAS, levels of sex steroids and physical changes were registered at each follow-up visit during a 3-year follow-up period, starting at the initiation of hormonal therapy. Data were analyzed cross-sectionally and prospectively. Over the first three months, we observed a decline in positive affect (PA) in both TM and TW. Thereafter, PA reached a steady state in TW, whereas in TM there was also a second decline at 18 months. In both TM and...

The Journal of clinical endocrinology and metabolism, Jan 20, 2017

Breast development is a key feature of feminization and therefore important to transwomen (male-t... more Breast development is a key feature of feminization and therefore important to transwomen (male-to-female transgender persons). However, it is not exactly known when breast development starts after initiating cross-sex hormone therapy (CHT) and how much growth may be expected of CHT alone. To investigate breast development in centimeters and bra cup-sizes in transwomen during their first year of CHT, and whether clinical or laboratory parameters predict the breast development. This study was performed as part of the European Network for the Investigation of Gender Incongruence (ENIGI), which is a prospective multicenter cohort study. Specialized gender clinics in Amsterdam, Ghent, and Florence. All transwomen who completed the first year of CHT (n=229) were eligible for analyses. Cross-sex hormone therapy. Breast development in centimeter and cup-size. The median age of the included transwomen was 28 years (range 18;69 years). Mean breast - chest difference increased from 4.1±2.9cm ...

European journal of endocrinology, Jan 28, 2017

Objective Cross-sex hormonal therapy (CHT) in trans persons affects their total body fat and tota... more Objective Cross-sex hormonal therapy (CHT) in trans persons affects their total body fat and total lean body mass. However, it is unknown how separate body regions are affected and whether these changes alter body shape. Therefore, the aim of this study is to determine the effects on body fat and lean body mass in separate body regions and on body shape after one year of CHT. Design and Methods In a multicenter prospective study at university hospitals, 179 male-to-female gender dysphoric persons, referred to as transwomen, and 162 female-to-male gender dysphoric persons, referred to as transmen, were included. All underwent whole body dual-energy X-ray absorptiometry and anthropometric measurements before and after one year of CHT. Results In transwomen, increases in body fat ranged from +18% (95%CI 13%;23%) in the android region to +42% (95%CI 37%;46%) in the leg region and +34% (95%CI 29%;38%) in the gynoid region. In transmen, changes in body fat ranged from -16% (95%CI -19;-14%...

LGBT Health, 2017

Purpose: Hormone treatment in trans women in Europe usually consists of the administration of est... more Purpose: Hormone treatment in trans women in Europe usually consists of the administration of estrogens and antiandrogens, for example, cyproterone acetate (CPA). Mild serum prolactin elevations during follow-up are attributed to estrogen therapy. This analysis evaluates whether CPA contributes to the elevation of prolactin in trans women receiving gender affirming hormones. Methods: This study is part of the endocrine part of the European Network for the Investigation of Gender Incongruence (ENIGI). Belgian data were selected for this substudy. Trans women who initiated gender affirming hormone treatment and underwent orchiectomy were prospectively evaluated. Trans women were treated with oral CPA 50 mg in combination with estrogen substitution. Postsurgery, estrogen was reinitiated in an unchanged dose. Sex steroids, gonadotropins, and prolactin were compared at baseline, pre-and postsurgery in patients receiving orchiectomy, and at baseline, 12, and 18 months in patients who did not undergo orchiectomy. Results: One hundred and seven trans women participated in this analysis, with a mean age of 31.5 years. An increase in serum prolactin levels was seen in the group undergoing orchiectomy (23.72 lg/L) and not undergoing orchiectomy (23.05 lg/L) at the preoperative and 12-month visit, compared with baseline (9.42 lg/L, P = 0.002 and 9.94 lg/L, P < 0.001, respectively). After orchiectomy, a decline in prolactin levels (10.17 lg/L, P < 0.001) occurred. Conclusions: CPA is likely to cause a temporary increase in serum prolactin, with prolactin levels returning to normal after orchiectomy and CPA discontinuation.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 29, 2017

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormo... more Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first-year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual-energy X-ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+...

Endocrine Abstracts, 2016

Endocrine Abstracts, 2016

The journal of sexual medicine, Jan 27, 2015

An increased risk of autistic traits in Klinefelter syndrome (KS) has been reported. In addition,... more An increased risk of autistic traits in Klinefelter syndrome (KS) has been reported. In addition, some studies have shown an increased incidence of gender dysphoria (GD) and paraphilia in autism spectrum disorder. The aim of this study was to evaluate the presence of (i) paraphilic fantasies and behaviors; and (ii) GD symptomatology in KS. A sample of 46 KS individuals and 43 healthy male controls (HC) were evaluated. Subjects were studied by means of several psychometric tests, such as Autism Spectrum Quotient (AQ) and Reading the Mind in the Eyes Revised (RME) to measure autistic traits, Gender Identity/GD questionnaire (GIDYQ-AA), and Sexual Addiction Screening Test (SAST). In addition, body uneasiness psychopathological symptoms were assessed using Symptom Checklist 90 Revised (SCL-90-R). The presence and frequency of any paraphilic fantasy and behavior was assessed by means of a clinical interview based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition crite...

The Journal of Sexual Medicine, 2014

Introduction. Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low p... more Introduction. Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low prevalence of gender dysphoria, small number of subjects treated at each center, lack of prospective studies, and wide variations in treatment modalities. Aim. The aim of this study is to report the short-term effects of CHT on hormonal and clinical changes, side effects, and adverse events in trans men (female-to-male gender dysphoric persons) and trans women (male-to-female gender dysphoric persons). Methods. This was a multicenter 1-year prospective study in 53 trans men and 53 trans women. Trans men received injections of testosterone undecanoate every 3 months. Trans women younger than 45 years received 50 mg cyproterone acetate (CA) and 4 mg estradiol valerate daily, whereas those older than 45 years received 50 mg CA daily together with 100 μg/24 hours transdermal 17-β estradiol. Main Outcome Measures. Sex steroids, prolactin, liver enzymes, lipids, hematocrit, blood pressure, anthropometrics, Ferriman and Gallwey score, and global acne grading scale were measured. Side effects, adverse events, and desired clinical changes were examined. Results. No deaths or severe adverse events were observed. Two trans men developed erythrocytosis, and two had transient elevation of the liver enzymes. Trans men reported an increase in sexual desire, voice instability, and clitoral pain (all P ≤ 0.01). Testosterone therapy increased acne scores, facial and body hair, and prevalence of androgenetic alopecia. Waist-hip ratio, muscle mass, triglycerides, total cholesterol (C), and LDL-C increased, whereas total body fat mass and HDL-C decreased. Three trans women experienced transient elevation of liver enzymes. A significant increase in breast tenderness, hot flashes, emotionality, and low sex drive was observed (all P ≤ 0.02). Fasting insulin, total body fat mass, and prolactin levels increased, and waist-hip ratio, lean mass, total C, and LDL-C decreased. Conclusions. Current treatment modalities were effective and carried a low risk for side effects and adverse events at short-time follow-up. Wierckx K, Van Caenegem E, Schreiner T, Haraldsen I, Fisher A, Toye K, Kaufman JM, and T'Sjoen G. Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: Results from the European Network for the Investigation of Gender Incongruence.

Sexual and Relationship Therapy, 2014

The commonly used Standards of Care for people with gender dysphoria, including those of the Worl... more The commonly used Standards of Care for people with gender dysphoria, including those of the World Professional Association for Transgender Health and The Royal College of Psychiatrists in the United Kingdom, as well as those standards used in many other countries, usually require that two signatures of approval from qualified mental health professionals be provided before genital reconstructive surgery (GRS) À sometimes called sexual reassignment surgery or gender confirmation surgery À is undertaken. This is different from surgeries which are similarly irreversible and remove reproductive capacity carried out on cisgender people. This paper explores the transspecific issues from a standpoint of medical ethics and argues that, provided sufficient safeguards are in place, including assessment within a multidisciplinary team, a nuanced approach utilising a single signature may instead be appropriate.

The Journal of Sexual Medicine, 2010

Introduction. We have recently reported that the perceived loss of a partner's sexual desire is i... more Introduction. We have recently reported that the perceived loss of a partner's sexual desire is independently associated with an increased incidence of major cardiovascular events in patients with erectile dysfunction (ED). No study has ever evaluated the specific impact of men's perception of women's sexual desire on male sexual function and lifestyle attitudes in ED subjects. Aim. To evaluate the clinical correlates of the perception of a partner's sexual desire [hypoactive sexual desire (HSD)] in a consecutive series of subjects seeking medical care for ED. Methods. A consecutive series of 2,303 heterosexual male patients (mean age 58.1 Ϯ 10.5) was studied. Main Outcome Measures. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) structured interview. They also completed the Middlesex Hospital Questionnaire, a brief questionnaire for the screening of the symptoms of mental disorders. Results. Among the patients studied, 458 (19.9%) reported a mild loss of their partner's desire, 302 (13.1%) a moderate reduction of libido, while 118 (5.1%) complained of a complete absence of sexual interest on the part of their partner. After adjustment for confounding factors, the perceived women's HSD was associated with different sexual, lifestyle, and relational factors. In particular, more extramarital affairs, a longer and more hostile couple relationship, as well as a stressful job and both alcohol and smoking abuse were all significantly associated with perceived women's HSD. In addition, the perceived women's moderate to severe HSD was significantly associated with severe ED and less frequent sexual intercourse. Finally, partner HSD was significantly associated with a stepwise increase of free-floating anxiety and depressive symptoms (adj. r = 0.081, P < 0.05 and 0.158, P < 0.0001, respectively). Conclusions. Perceived sexual interest (éros) on the part of the woman can be seen for men not only as a fun and enjoyable behavior, but also a safe strategy for improving a man's overall health and life expectancy.

The Journal of Sexual Medicine, 2009

The Journal of Sexual Medicine, 2016

Finally, GIDYQ-AA was significantly lower in the GD group (meaning a higher level of GD, t ¼-17.8... more Finally, GIDYQ-AA was significantly lower in the GD group (meaning a higher level of GD, t ¼-17.82; p 0.0001). Conclusion: GD adolescents report significant psychological impairment in social and psychological functioning and higher suicidal risk compared to subjects without GD. In addition, results confirmed the presence of higher levels of body uneasiness in adolescents with GD.

Journal of Endocrinological Investigation

Purpose We evaluated differences in Autism Spectrum Quotient (AQ) scores between a sample of horm... more Purpose We evaluated differences in Autism Spectrum Quotient (AQ) scores between a sample of hormone-naïve transgender and cisgender people and the impact of gender-affirming hormonal treatment (GAHT) on AQ scores across time. Furthermore, we assessed alexithymia and social anxiety as possible mediators of changes in AQ scores. Methods A cross-sectional comparison between cisgender and transgender people before GAHT and a prospective study on the effects of GAHT over time were performed. Transgender and cisgender people completed several psychometric tests. A total sample of 789 persons (n = 229 cismen; n = 172 ciswomen; n = 206 transmen; n = 182 transwomen) referring to the Florence and Rome Gender Clinics between 2018 and 2020 was enrolled. Of these, 62 participants referring to the Florence Gender Clinic were evaluated in a prospective study at baseline and 12 months after GAHT. Results Groups showed significant differences in terms of autistic traits: ciswomen showed lower score...

Endocrine Abstracts, 2018

Journal of Clinical Medicine, 2022

Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgende... more Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgender people is limited. For this reason, in 2010 the European Network for the Investigation of Gender Incongruence (ENIGI) study was born. The aim of this review is to summarize evidence emerging from this prospective multicentric study and to identify future perspectives. GAHT was effective in inducing desired body changes in both trans AMAB and AFAB people (assigned male and female at birth, respectively). Evidence from the ENIGI study confirmed the overall safety of GAHT in the short/mid-term. In trans AMAB people, an increase in prolactin levels was demonstrated, whereas the most common side effects in trans AFAB people were acne development, erythrocytosis, and unfavorable changes in lipid profile. The main future perspectives should include the evaluation of the efficacy and safety of non-standardized hormonal treatment in non-binary trans people. Furthermore, long-term safety data on...

The Journal of Sexual Medicine, 2021

BACKGROUND Over the last few years, the gender binary has been questioned, highlighting the exist... more BACKGROUND Over the last few years, the gender binary has been questioned, highlighting the existence of gender diverse people, who identify as neither (exclusively) male nor female. AIM The present study evaluated the possible differences in terms of psychological wellbeing between binary and gender diverse individuals, as well as the role of perceived social acceptance and religious fundamentalism as possible mediators of psychopathology in gender diverse people. Furthermore, the diversity of gender-affirming hormonal treatment requests according to gender identification was investigated. METHODS A sample of 563 transgender people aged 18-70 was enrolled (n = 264 assigned female at birth, AFAB and n = 299 assigned male at birth, AMAB), all individuals referring to several Italian gender clinics. A subdivision of the study population based on the gender identity visual analog scale (GI-VAS) median was performed, in order to distinguish between gender diverse and binary transgender individuals. Moreover, a linear regression analysis was performed entering logarithmically transformed GI-VAS (Log GI-VAS) into the models with psychometric scales. OUTCOMES Psychometric and sociodemographic data, as well as information regarding requests for gender-affirming treatments, were extrapolated from the clinical interviews conducted during the first referral. RESULTS Gender diverse individuals showed significantly less intense gender dysphoria and higher levels of depression and anxiety compared to binary ones; accordingly, a less binary gender identity correlated with higher levels of depression and anxiety and lower levels of gender dysphoria. The depressive symptomatology in gender diverse people was partially mediated by perceived discrimination and humiliation. Moreover, gender diverse AMAB people sought a non-standard hormonal treatment more often than their binary counterpart. CLINICAL IMPLICATIONS The present study highlights the importance for transgender health professionals, when planning gender-affirming hormonal treatments, to offer flexible interventions, tailored on the patient's needs and goals. STRENGTHS & LIMITATIONS Strengths included exploring whether and how perceived discrimination may affect mental health in gender diverse people. Limitations included the enrolled sample of people referring to different gender clinics, which is not fully representative of the transgender population. CONCLUSION This study highlights the importance of evaluating each individual's unique health care needs, exploring each single request and its underlying reasons. Romani A., Mazzoli F., Ristori J., et al. Psychological Wellbeing and Perceived Social Acceptance in Gender Diverse Individuals. J Sex Med 2021;18:1933-1944.

The Journal of Clinical Endocrinology & Metabolism, 2021

Context Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts ... more Context Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent. Objective To assess the lowest effective dose of CPA in trans women to prevent side effects. Methods This longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n = 882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of...

The Journal of Sexual Medicine, 2021

BACKGROUND Cardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAH... more BACKGROUND Cardiovascular (CV) implications of long-term gender affirming hormonal treatment (GAHT) in transgender individuals still remain largely unknown. AIM To evaluate changes in the 30-year Framingham cardiovascular disease (CVD) risk in a large cohort of transgender individuals after the start of GAHT. METHODS In a multicenter prospective study, a consecutive series of 309 participants (165 transmen and 144 transwomen) was evaluated during a 2-year follow-up. Prospectively, after the start of GAHT a physical examination was performed and blood samples were drawn. CVD risk was calculated for each person, according to the Framingham 30-year CVD risk estimate. MAIN OUTCOME MEASURE Changes in CV risk factors and 30-year Framingham CVD risk during GAHT. CLINICAL IMPLICATIONS In transmen testosterone-induced lipid profile alterations may have a clinical relevance on the individual long-term CVD risk. STRENGTHS & LIMITATIONS The strength of the present study is the possibility to predict long-term CV outcomes in transgender individuals receiving GAHT based on a short observation; whereas the main limitation is that CVD risk prospective changes mainly represent the expression of risk factors changes during GAHT. RESULTS In transwomen a significant decrease in triglycerides, total cholesterol and LDL-cholesterol was observed during the 2-year follow-up (P < .05), whereas unfavorable lipid changes - such as increased total cholesterol, triglycerides, and LDL cholesterol levels and decreased HDL cholesterol levels (P < .05)- occurred after the start of GAHT in transmen. These changes in risk factors led to an increase in the risk of general and hard CVD events based on lipid profile over time in transmen (P = .001 and P = .005, respectively). No significant changes in general and hard CVD risk based on lipid profile were observed in transwomen over time. CONCLUSIONS Our findings confirmed the unfavorable lipid changes in transmen after the start of GAHT even during a longer follow-up, empathizing the potential clinical impact of these modifications on individual long-term CVD risk. Cocchetti C, Castellini G, Iacuaniello D, et al. Does Gender-Affirming Hormonal Treatment Affect 30-Year Cardiovascular Risk in Transgender Persons? A Two-Year Prospective European Study (ENIGI). J Sex Med 2021;xxx:xxx-xxx.

The Journal of Clinical Endocrinology & Metabolism, 2021

Introduction Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease... more Introduction Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease and is influenced by sex hormones. Our aim was to investigate changes in visceral fat and the ratio of visceral fat to total body fat (VAT/TBF) and their associations with changes in lipids and insulin resistance after 1 year of hormone therapy in trans persons. Methods In 179 trans women and 162 trans men, changes in total body and visceral fat estimated with dual-energy X-ray absorptiometry before and after 1 year of hormone therapy were related to lipids and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] with linear regression analysis. Results In trans women, total body fat increased by 4.0 kg (95% CI 3.4, 4.7), while the amount of visceral fat did not change (−2 grams; 95% CI −15, 11), albeit with a large range from −318 to 281, resulting in a decrease in the VAT/TBF ratio of 17% (95% CI 15, 19). In trans men, total body fat decreased with 2.8 kg ...

Journal of Clinical Medicine, 2021

Improving transgender people’s quality of life (QoL) is the most important goal of gender-affirmi... more Improving transgender people’s quality of life (QoL) is the most important goal of gender-affirming care. Prospective changes in affect can influence QoL. We aim to assess the impact of initiating gender-affirming hormonal treatment (HT) on affect. In the European Network for the Investigation of Gender Incongruence (ENIGI) study, we prospectively collected data of 873 participants (451 transwomen (TW) and 422 transmen (TM)). At baseline, psychological questionnaires including the Positive and Negative Affect Schedule (PANAS) were administered. The PANAS, levels of sex steroids and physical changes were registered at each follow-up visit during a 3-year follow-up period, starting at the initiation of hormonal therapy. Data were analyzed cross-sectionally and prospectively. Over the first three months, we observed a decline in positive affect (PA) in both TM and TW. Thereafter, PA reached a steady state in TW, whereas in TM there was also a second decline at 18 months. In both TM and...

The Journal of clinical endocrinology and metabolism, Jan 20, 2017

Breast development is a key feature of feminization and therefore important to transwomen (male-t... more Breast development is a key feature of feminization and therefore important to transwomen (male-to-female transgender persons). However, it is not exactly known when breast development starts after initiating cross-sex hormone therapy (CHT) and how much growth may be expected of CHT alone. To investigate breast development in centimeters and bra cup-sizes in transwomen during their first year of CHT, and whether clinical or laboratory parameters predict the breast development. This study was performed as part of the European Network for the Investigation of Gender Incongruence (ENIGI), which is a prospective multicenter cohort study. Specialized gender clinics in Amsterdam, Ghent, and Florence. All transwomen who completed the first year of CHT (n=229) were eligible for analyses. Cross-sex hormone therapy. Breast development in centimeter and cup-size. The median age of the included transwomen was 28 years (range 18;69 years). Mean breast - chest difference increased from 4.1±2.9cm ...

European journal of endocrinology, Jan 28, 2017

Objective Cross-sex hormonal therapy (CHT) in trans persons affects their total body fat and tota... more Objective Cross-sex hormonal therapy (CHT) in trans persons affects their total body fat and total lean body mass. However, it is unknown how separate body regions are affected and whether these changes alter body shape. Therefore, the aim of this study is to determine the effects on body fat and lean body mass in separate body regions and on body shape after one year of CHT. Design and Methods In a multicenter prospective study at university hospitals, 179 male-to-female gender dysphoric persons, referred to as transwomen, and 162 female-to-male gender dysphoric persons, referred to as transmen, were included. All underwent whole body dual-energy X-ray absorptiometry and anthropometric measurements before and after one year of CHT. Results In transwomen, increases in body fat ranged from +18% (95%CI 13%;23%) in the android region to +42% (95%CI 37%;46%) in the leg region and +34% (95%CI 29%;38%) in the gynoid region. In transmen, changes in body fat ranged from -16% (95%CI -19;-14%...

LGBT Health, 2017

Purpose: Hormone treatment in trans women in Europe usually consists of the administration of est... more Purpose: Hormone treatment in trans women in Europe usually consists of the administration of estrogens and antiandrogens, for example, cyproterone acetate (CPA). Mild serum prolactin elevations during follow-up are attributed to estrogen therapy. This analysis evaluates whether CPA contributes to the elevation of prolactin in trans women receiving gender affirming hormones. Methods: This study is part of the endocrine part of the European Network for the Investigation of Gender Incongruence (ENIGI). Belgian data were selected for this substudy. Trans women who initiated gender affirming hormone treatment and underwent orchiectomy were prospectively evaluated. Trans women were treated with oral CPA 50 mg in combination with estrogen substitution. Postsurgery, estrogen was reinitiated in an unchanged dose. Sex steroids, gonadotropins, and prolactin were compared at baseline, pre-and postsurgery in patients receiving orchiectomy, and at baseline, 12, and 18 months in patients who did not undergo orchiectomy. Results: One hundred and seven trans women participated in this analysis, with a mean age of 31.5 years. An increase in serum prolactin levels was seen in the group undergoing orchiectomy (23.72 lg/L) and not undergoing orchiectomy (23.05 lg/L) at the preoperative and 12-month visit, compared with baseline (9.42 lg/L, P = 0.002 and 9.94 lg/L, P < 0.001, respectively). After orchiectomy, a decline in prolactin levels (10.17 lg/L, P < 0.001) occurred. Conclusions: CPA is likely to cause a temporary increase in serum prolactin, with prolactin levels returning to normal after orchiectomy and CPA discontinuation.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 29, 2017

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormo... more Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first-year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual-energy X-ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+...

Endocrine Abstracts, 2016

Endocrine Abstracts, 2016

The journal of sexual medicine, Jan 27, 2015

An increased risk of autistic traits in Klinefelter syndrome (KS) has been reported. In addition,... more An increased risk of autistic traits in Klinefelter syndrome (KS) has been reported. In addition, some studies have shown an increased incidence of gender dysphoria (GD) and paraphilia in autism spectrum disorder. The aim of this study was to evaluate the presence of (i) paraphilic fantasies and behaviors; and (ii) GD symptomatology in KS. A sample of 46 KS individuals and 43 healthy male controls (HC) were evaluated. Subjects were studied by means of several psychometric tests, such as Autism Spectrum Quotient (AQ) and Reading the Mind in the Eyes Revised (RME) to measure autistic traits, Gender Identity/GD questionnaire (GIDYQ-AA), and Sexual Addiction Screening Test (SAST). In addition, body uneasiness psychopathological symptoms were assessed using Symptom Checklist 90 Revised (SCL-90-R). The presence and frequency of any paraphilic fantasy and behavior was assessed by means of a clinical interview based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition crite...

The Journal of Sexual Medicine, 2014

Introduction. Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low p... more Introduction. Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low prevalence of gender dysphoria, small number of subjects treated at each center, lack of prospective studies, and wide variations in treatment modalities. Aim. The aim of this study is to report the short-term effects of CHT on hormonal and clinical changes, side effects, and adverse events in trans men (female-to-male gender dysphoric persons) and trans women (male-to-female gender dysphoric persons). Methods. This was a multicenter 1-year prospective study in 53 trans men and 53 trans women. Trans men received injections of testosterone undecanoate every 3 months. Trans women younger than 45 years received 50 mg cyproterone acetate (CA) and 4 mg estradiol valerate daily, whereas those older than 45 years received 50 mg CA daily together with 100 μg/24 hours transdermal 17-β estradiol. Main Outcome Measures. Sex steroids, prolactin, liver enzymes, lipids, hematocrit, blood pressure, anthropometrics, Ferriman and Gallwey score, and global acne grading scale were measured. Side effects, adverse events, and desired clinical changes were examined. Results. No deaths or severe adverse events were observed. Two trans men developed erythrocytosis, and two had transient elevation of the liver enzymes. Trans men reported an increase in sexual desire, voice instability, and clitoral pain (all P ≤ 0.01). Testosterone therapy increased acne scores, facial and body hair, and prevalence of androgenetic alopecia. Waist-hip ratio, muscle mass, triglycerides, total cholesterol (C), and LDL-C increased, whereas total body fat mass and HDL-C decreased. Three trans women experienced transient elevation of liver enzymes. A significant increase in breast tenderness, hot flashes, emotionality, and low sex drive was observed (all P ≤ 0.02). Fasting insulin, total body fat mass, and prolactin levels increased, and waist-hip ratio, lean mass, total C, and LDL-C decreased. Conclusions. Current treatment modalities were effective and carried a low risk for side effects and adverse events at short-time follow-up. Wierckx K, Van Caenegem E, Schreiner T, Haraldsen I, Fisher A, Toye K, Kaufman JM, and T'Sjoen G. Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: Results from the European Network for the Investigation of Gender Incongruence.

Sexual and Relationship Therapy, 2014

The commonly used Standards of Care for people with gender dysphoria, including those of the Worl... more The commonly used Standards of Care for people with gender dysphoria, including those of the World Professional Association for Transgender Health and The Royal College of Psychiatrists in the United Kingdom, as well as those standards used in many other countries, usually require that two signatures of approval from qualified mental health professionals be provided before genital reconstructive surgery (GRS) À sometimes called sexual reassignment surgery or gender confirmation surgery À is undertaken. This is different from surgeries which are similarly irreversible and remove reproductive capacity carried out on cisgender people. This paper explores the transspecific issues from a standpoint of medical ethics and argues that, provided sufficient safeguards are in place, including assessment within a multidisciplinary team, a nuanced approach utilising a single signature may instead be appropriate.

The Journal of Sexual Medicine, 2010

Introduction. We have recently reported that the perceived loss of a partner's sexual desire is i... more Introduction. We have recently reported that the perceived loss of a partner's sexual desire is independently associated with an increased incidence of major cardiovascular events in patients with erectile dysfunction (ED). No study has ever evaluated the specific impact of men's perception of women's sexual desire on male sexual function and lifestyle attitudes in ED subjects. Aim. To evaluate the clinical correlates of the perception of a partner's sexual desire [hypoactive sexual desire (HSD)] in a consecutive series of subjects seeking medical care for ED. Methods. A consecutive series of 2,303 heterosexual male patients (mean age 58.1 Ϯ 10.5) was studied. Main Outcome Measures. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) structured interview. They also completed the Middlesex Hospital Questionnaire, a brief questionnaire for the screening of the symptoms of mental disorders. Results. Among the patients studied, 458 (19.9%) reported a mild loss of their partner's desire, 302 (13.1%) a moderate reduction of libido, while 118 (5.1%) complained of a complete absence of sexual interest on the part of their partner. After adjustment for confounding factors, the perceived women's HSD was associated with different sexual, lifestyle, and relational factors. In particular, more extramarital affairs, a longer and more hostile couple relationship, as well as a stressful job and both alcohol and smoking abuse were all significantly associated with perceived women's HSD. In addition, the perceived women's moderate to severe HSD was significantly associated with severe ED and less frequent sexual intercourse. Finally, partner HSD was significantly associated with a stepwise increase of free-floating anxiety and depressive symptoms (adj. r = 0.081, P < 0.05 and 0.158, P < 0.0001, respectively). Conclusions. Perceived sexual interest (éros) on the part of the woman can be seen for men not only as a fun and enjoyable behavior, but also a safe strategy for improving a man's overall health and life expectancy.

The Journal of Sexual Medicine, 2009

The Journal of Sexual Medicine, 2016

Finally, GIDYQ-AA was significantly lower in the GD group (meaning a higher level of GD, t ¼-17.8... more Finally, GIDYQ-AA was significantly lower in the GD group (meaning a higher level of GD, t ¼-17.82; p 0.0001). Conclusion: GD adolescents report significant psychological impairment in social and psychological functioning and higher suicidal risk compared to subjects without GD. In addition, results confirmed the presence of higher levels of body uneasiness in adolescents with GD.

Journal of Endocrinological Investigation

Purpose We evaluated differences in Autism Spectrum Quotient (AQ) scores between a sample of horm... more Purpose We evaluated differences in Autism Spectrum Quotient (AQ) scores between a sample of hormone-naïve transgender and cisgender people and the impact of gender-affirming hormonal treatment (GAHT) on AQ scores across time. Furthermore, we assessed alexithymia and social anxiety as possible mediators of changes in AQ scores. Methods A cross-sectional comparison between cisgender and transgender people before GAHT and a prospective study on the effects of GAHT over time were performed. Transgender and cisgender people completed several psychometric tests. A total sample of 789 persons (n = 229 cismen; n = 172 ciswomen; n = 206 transmen; n = 182 transwomen) referring to the Florence and Rome Gender Clinics between 2018 and 2020 was enrolled. Of these, 62 participants referring to the Florence Gender Clinic were evaluated in a prospective study at baseline and 12 months after GAHT. Results Groups showed significant differences in terms of autistic traits: ciswomen showed lower score...