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Context: The effects of androgen therapy on arterial function in transgender men (TM) are not fully understood, particularly concerning long-term androgen treatment. Objective: To evaluate arterial stiffness in TM receiving long-term gender-affirming hormone therapy by carotid-femoral pulse wave velocity (cf-PWV). Methods: A cross-sectional case-control study at the Gender Dysphoria Unit of the Division of Endocrinology, HC-FMUSP, Sao Paulo, Brazil. Thirty-three TM receiving intramuscular testosterone esters as regular treatment for an average time of 14 ± 8 years were compared with 111 healthy cisgender men and women controls matched for age and body mass index. Aortic stiffness was evaluated by cf-PWV measurements using Complior device post-testosterone therapy. The main outcome measure was aortic stiffness by cf-PWV as a cardiovascular risk marker in TM and control group. Results: The cf-PWV after long-term testosterone therapy was significantly higher in TM (7.4 ± 0.9 m/s; range 5.8-8.9 m/s) than in cisgender men (6.6 ± 1.0 m/s; range 3.8-9.0 m/s, P < .01) and cisgender women controls (6.9 ± .9 m/s; range 4.8-9.1 m/s, P = .02). The cf-PWV was significantly and positively correlated with age. Analysis using blood pressure as a covariate showed a significant relationship between TM systolic blood pressure (SBP) and cf-PWV in relation to cisgender women but not to cisgender men. Age, SBP, and diagnosis of hypertension were independently associated with cf-PWV in the TM group. Conclusion: The TM group on long-term treatment with testosterone had higher aging-related aortic stiffening than the control groups. These findings indicate that aortic stiffness might be accelerated in the TM group receiving gender-affirming hormone treatment, and suggest a potential deleterious effect of testosterone on arterial function. Preventive measures in TM individuals receiving testosterone treatment, who are at higher risk for cardiovascular events, are highly recommended.

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BACKGROUND: Mastectomy is performed in female-to-male transsexual (FTM TS) patients as a surgical treatment to make a female thorax resemble a male thorax; however, no studies have examined the nipple-areolar complex (NAC) position in FTM TS patients after mastectomy. PATIENTS AND METHODS: The NAC position in 41 FTM TS patients before and after non-skin-excisional mastectomy was examined and compared with that in 50 age- and BMI-matched biologically male subjects as controls. The factors affecting the NAC position after the operation were also examined and verified by multiple regression analysis. RESULTS AND CONCLUSIONS: After non-skin-excisional mastectomy, the NAC in the FTM TS patients was positioned significantly more medially (horizontal NAC position ratio {('internipple distance'/'width of thorax') × 100} [HNPR]: preoperatively, 70.07% ± 4.19%; postoperatively, 63.28% ± 3.79%) and cranially (vertical NAC position ratio {('distance from sternal notch to nipple height'/'distance from sternal notch to umbilicus') × 100} [VNPR]: preoperatively, 43.87% ± 3.68%; postoperatively, 41.37% ± 3.15%). Postoperatively, the NAC in the FTM TS patients was located significantly more medially than that in the control subjects (HNPR: 63.28% ± 3.79% to 66.79% ± 4.82%), although the height of the NAC was the same. Multiple regression analysis revealed that the NAC position on breasts characterized by ptosis, a high projection, and lateral leaning (low skin elasticity and a substantial amount of skin between the nipples) tended to be positioned more medially after non-skin-excisional mastectomy. Laterally deviated eccentric circular type mastectomy may be a good option for FTM TS patients who have moderately sized breasts with such features. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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BACKGROUND: Although phalloplasty with a free radial forearm (RF) flap is the gold standard for sex reassignment surgery in female-to-male transsexuals, it can result in unsightly scars, lymphedema, and numbness of the hand. AIM: To introduce the concept of flap combination phalloplasty and its clinical application. METHODS: This is a retrospective chart review study of patients undergoing phalloplasty using various multiple flaps. Demographic data, surgical data, and outcomes were recorded. OUTCOMES: Of the 15 cases, 5 were urethral fistulas; 4 were venous thrombosis; 2 were urethral calculus; and 1 was a partial flap loss. RESULTS: 15 patients were included (age range 25-43 years, median 34 years). An RF flap and a deep inferior epigastric artery perforator flap combination were most frequently used. The median operative time for flap combination phalloplasty was 10.5 hours (range 6.5-12.5 hours). There was no total flap necrosis, but there was 1 case of partial flap loss. There were urethral fistulas in 5, venous thrombosis in 4, and urethral calculus in 2 cases. CLINICAL IMPLICATIONS: Flap combination phalloplasty will become the third option when both the RF flap and the anterolateral thigh pedicle flap are not useful. STRENGTH & LIMITATIONS: Flap combination phalloplasty is a complex operative procedure with a prolonged operative time, but it can provide more flap selection and reduce the morbidity at each donor site. Choosing from many different options can be beneficial to patients. CONCLUSION: Flap combination phalloplasty has a similar complication rate to other procedures and has advantages in terms of flexibility and less donor site morbidity; it may thus be an option when either the RF flap or the anterolateral thigh pedicle flap cannot be used. Namba Y, Watanabe T, Kimata Y. Flap Combination Phalloplasty in Female-to-Male Transsexuals. J Sex Med 2019;16:934-941.

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A trans-male (TM) is a biologically female person with male gender identity who wishes to acquire male sexual characteristics and fulfil a male social role. To achieve that purpose, both cross-hormonal therapy (CHT) and surgical phalloplasty can be used. We evaluated the short term (12 months) safety profile of CHT using different forms of testosterone available for prescription in Argentina. In this retrospective study, we analyzed the medical history of 30 trans-male patients fitting the inclusion criteria. The mean age of the population was 27 years. The mean basal serum level of testosterone was 0.43 ng/ml, which increased to 6.36 ng/ml (male hormonal levels). The hematocrit increased from a baseline of 40.0 to 45.2% (p < 0.01) and hemoglobin increased from 13.6 to 15.2 g/dl (p < 0.01). Total cholesterol remained stable with values of 175 and 185 mg/dl (p = 0.81). There were no significant changes in serum triglycerides: 88.3 and 102 mg/dl (p = 0.08). LDL increased in the first 6 to 12 months of CHT from 101.2 to 112.5 mg/dl (p = 0.17). At 12 months HDL levels increased from 50.1 to 52 mg/dl (p < 0.01). Hepatic enzymes remained stable. There is no available data regarding safety of testosterone use in TM in our country. In no case did we need to suspend the medication due to unwanted effects.

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Se denomina trans-varón (TV) a una persona de sexo biológico femenino con identidad de género masculino. Para adquirir caracteres sexuales y expresar un rol social semejante podría utilizarse: terapia hormonal cruzada (THC) y/o genitoplastia masculinizante. Se evaluó el perfil de seguridad a corto plazo (primer año) de la THC con las distintas formas farmacéuticas de testosterona disponibles en nuestro país. El estudio se realizó de manera retrospectiva, analizando las historias clínicas de 30 pacientes trans-varón que cumplían con los requisitos para ser incluidos. La edad media de la población fue de 27 años. La media basal de testosterona fue de 0.43 ng/ml, que luego aumentó a 6.36 ng/ml (valores normales para sexo masculino). El hematocrito incrementó de su valor basal 40.0 a 45.2% (p < 0.01) mientras la Hb de 13.6 a 15.2 g/dl (p < 0.01). El colesterol total se mantuvo estable con valores de 175 y 185 mg/dl (p = 0.81). No hubo cambios significativos en triglicéridos: 88.3 y 102 mg/dl (p = 0.08). El colesterol LDL incrementó en los primeros 6 a 12 meses de THC de 101.2 a 112.5 mg/dl (p = 0.17). A los 12 meses los niveles de colesterol HDL aumentaron de 50.1 a 52.0 mg/ dl (p < 0.01). Las enzimas hepáticas se mantuvieron estables. No existen datos en nuestro país sobre seguridad de la testosterona en TV. No tuvimos necesidad de suspender la medicación por efectos no deseados en los parámetros estudiados.

A trans-male (TM) is a biologically female person with male gender identity who wishes to acquire male sexual characteristics and fulfil a male social role. To achieve that purpose, both cross-hormonal therapy (CHT) and surgical phalloplasty can be used. We evaluated the short term (12 months) safety profile of CHT using different forms of testosterone available for prescription in Argentina. In this retrospective study, we analyzed the medical history of 30 trans-male patients fitting the inclusion criteria. The mean age of the population was 27 years. The mean basal serum level of testosterone was 0.43 ng/ml, which increased to 6.36 ng/ml (male hormonal levels). The hematocrit increased from a baseline of 40.0 to 45.2% (p < 0.01) and hemoglobin increased from 13.6 to 15.2 g/dl (p < 0.01). Total cholesterol remained stable with values of 175 and 185 mg/dl (p = 0.81). There were no significant changes in serum triglycerides: 88.3 and 102 mg/dl (p = 0.08). LDL increased in the first 6 to 12 months of CHT from 101.2 to 112.5 mg/dl (p = 0.17). At 12 months HDL levels increased from 50.1 to 52 mg/dl (p < 0.01). Hepatic enzymes remained stable. There is no available data regarding safety of testosterone use in TM in our country. In no case did we need to suspend the medication due to unwanted effects.

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OBJECTIVES: This study aims to evaluate the currently available discursive and empirical data relating to those aspects of transmasculine people's vocal situations that are not primarily gender-related, to identify restrictions to voice function that have been observed in this population, and to make suggestions for future voice research and clinical practice. METHODS: We conducted a comprehensive review of the voice literature. Publications were identified by searching six electronic databases and bibliographies of relevant articles. Twenty-two publications met inclusion criteria. Discourses and empirical data were analyzed for factors and practices that impact on voice function and for indications of voice function-related problems in transmasculine people. The quality of the evidence was appraised. RESULTS: The extent and quality of studies investigating transmasculine people's voice function was found to be limited. There was mixed evidence to suggest that transmasculine people might experience restrictions to a range of domains of voice function, including vocal power, vocal control/stability, glottal function, pitch range/variability, vocal endurance, and voice quality. CONCLUSIONS: More research into the different factors and practices affecting transmasculine people's voice function that takes account of a range of parameters of voice function and considers participants' self-evaluations is needed to establish how functional voice production can be best supported in this population.

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OBJECTIVES: To investigate effects of testosterone treatment regarding voice virilization, voice problems, and voice satisfaction in transsexual female-to-male individuals, referred to as trans men. STUDY DESIGN: Longitudinal. METHODS: Fifty trans men, diagnosed with transsexualism, 18-64 years, met the inclusion criteria. Voice data before treatment and after 3, 6, or 12 months were available from 49 participants, and for 28 participants also after 18 and/or 24 months of treatment. Digital audio recordings of speech range profiles and voice range profiles were carried out in a sound-treated booth following clinical routines. Acoustic analyses of fundamental frequency (F0) and sound pressure level were made. Endocrine data and answers from questionnaires concerning voice function and voice problems were collected from medical records. RESULTS: Mean F0 and mode F0 of the habitual voice decreased significantly after 3 months, 6 months, and up to 12 months, when group data were congruent with reference data for males. Mean F0 was 125 Hz after 12 months with a large interindividual variation. Sound pressure level values did not change significantly. Voice satisfaction correlated with lower F0 values. Twenty-four percent of the participants reported voice symptoms, for example, vocal instability and fatigue, and had received voice therapy. F0 values did not correlate with androgen levels. CONCLUSIONS: Most trans men developed a male voice and were satisfied. However, it is important to detect the substantial group of trans men with voice problems and with insufficient voice virilization and who may need voice therapy. Therefore, we recommend systematic voice assessments during testosterone treatment.

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PURPOSE: Construction of a neourethra is always considered to be a difficult part in phalloplasty, especially for the female-to-male (FTM) transsexual patients. We report our experience with prefabricated pars pendulans urethrae using vaginal mucosal graft for phalloplasty in FTM transsexuals. MATERIALS AND METHODS: We retrospectively reviewed notes on the 22 FTM patients treated with pedicled-flap phalloplasty with prefabricated pars pendulans urethrae using vaginal mucosal graft between January 2008 and December 2012. Surgical outcome, urological function, and complications were recorded. Histological difference between normal mucosa and skin, and pathological changes of vaginal mucosal graft were also observed. RESULTS: All the reconstructive penis survived, and patients could void in a standing position finally at a median follow-up of 25.4 ± 6.0 months. Urethral fistula and urethral stricture rates were 31.8 % (7/22 patients) and 4.5 % (1/22 patients), respectively. The occurrence of the urethral stricture was remarkably low compared with previous reports. Our histological results also showed a pronounced similarity between vaginal and buccal mucosa. Morphologically, they resembled urethral epithelium more closely than the forearm skin. Following the free transfer, the vaginal mucosal graft also showed a good revascularization and the inflammatory reaction and the extent of fibrosis of the mucosa decreased to the normal level after a 6-month prefabrication. CONCLUSION: With prefabrication of vaginal mucosal graft, we reconstruct a competent phallic neourethra in these FTM transsexuals. According to its histological similarities and source character, the vaginal mucosa is the excellent substitute material for promising urethral reconstruction in FTM transsexuals.

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Cross-sex hormone treatment of transgender persons is usually uneventful, but hormone-sensitive malignancies of the (reproductive) organs of the natal and new sex (breasts, neovagina) may arise. Sex reassignment surgery impacts on the urodynamics of the reassigned sex. Pathology originating from organ systems of the natal sex may be overlooked in the new sex. In male-to-female transgender individuals, malignant tumors of the breasts and prostate may occur. Neovaginas are constructed with skin or sigmoid. Shortening of the male urethra to female dimensions is usually uneventful. In female-to-male transgender individuals breast cancer may develop, sometimes in residual mammary tissue after reductive mammoplasty. Malignancies of the vagina and ovaries are rare. Testosterone may be aromatized to estrogens, with effects on the endometrium. Lengthening of the female urethra to male dimensions may cause urethral fistulae, urethral strictures, and meatal stenoses. A degree of post-voiding incontinence may occur.

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BACKGROUND: Transmasculine people assigned female sex at birth but who do not identify with this classification have traditionally received little consideration in the voice literature. Some voice researchers and clinicians suggest that transmasculine people do not need attention because testosterone treatment leads to a satisfactory masculinization of their voice organs and voices. Others, however, argue that transmasculine people are a heterogeneous group whose members might not share the same body type, gender identity or desire for medical approaches to gender transitioning. Therefore, testosterone-induced voice changes may not necessarily meet the needs and expectations of all transmasculine people. AIMS: To evaluate the gender-related discursive and empirical data about transmasculine people's vocal situations to identify gaps in the current state of knowledge and to make suggestions for future voice research and clinical practice. METHODS & PROCEDURES: A comprehensive review of peer-reviewed academic and clinical literature was conducted. Publications were identified by searching seven electronic databases and bibliographies of relevant articles. Thirty-one publications met inclusion criteria. Discourses and empirical data were analysed thematically. Potential problem areas that transmasculine people may experience were identified and the quality of evidence appraised. MAIN CONTRIBUTION: The extent and quality of voice research conducted with transmasculine people so far was found to be limited. There was mixed evidence to suggest that transmasculine people's vocal situations could be regarded as problematic. The diversity that characterizes the transmasculine population received little attention and the complexity of the factors that contribute to a successful or unsuccessful vocal communication of gender in this group appeared to be under-researched. While most transmasculine people treated with testosterone can expect a lowering of their pitch, it remains unclear whether the extent of the pitch change is enough to result in a voice that is recognized by others as male. CONCLUSIONS & IMPLICATIONS: More research into the different factors affecting transmasculine people's vocal situations that takes account of the diversity within the population is needed.

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INTRODUCTION: Our knowledge concerning the effects of testosterone (T) therapy on the skin of trans men (female-to-male transsexuals) is scarce. AIM: The aim of this study was to evaluate the short- and long-term clinical effects of T treatment on the skin of trans men. METHODS: We conducted a prospective intervention study in 20 hormone naive trans men and a cross-sectional study in 50 trans men with an average of 10 years on T therapy. MAIN OUTCOME MEASURES: Acne lesions were assessed using the Gradual Acne Grading Scale, hair patterns using the Ferriman and Gallwey classification (F&G), and androgenetic alopecia using the Norwood Hamilton Scale. RESULTS: T treatment increased facial and body hair growth. The F&G score increased progressively from a median value of 0.5 at baseline to a value of 12 after 12 months of T administration. After long-term T treatment, all but one trans man achieved an F&G score indicative of hirsutism in women, with a median value of 24. Only one trans man acquired mild frontotemporal hair loss during the first year of T treatment, whereas 32.7% of trans men had mild frontotemporal hair loss and 31% had moderate to severe androgenetic alopecia after long-term T therapy. The presence and severity of acne increased during the first year of T therapy, and peaked at 6 months. After long-term T treatment, most participants had no or mild acne lesions (93.9%). Dermatological outcome was not demonstrably related to individual serum T or dihydrotestosterone levels. CONCLUSIONS: T treatment increased facial and body hair in a time-dependent manner. The prevalence and severity of acne in the majority of trans men peaked 6 months after beginning T therapy. Severe skin problems were absent after short- and long-term T treatment.

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INTRODUCTION: Transsexual people receive cross-sex hormones as part of their treatment, potentially inducing hormone-sensitive malignancies. AIM: To examine the occurrence of breast cancer in a large cohort of Dutch male and female transsexual persons, also evaluating whether the epidemiology accords with the natal sex or the new sex. MAIN OUTCOME MEASURE: Number of people with breast cancer between 1975 and 2011. METHODS: We researched the occurrence of breast cancer among transsexual persons 18-80 years with an exposure to cross-sex hormones between 5 to >30 years. Our study included 2,307 male-to-female (MtF) transsexual persons undergoing androgen deprivation and estrogen administration (52,370 person-years of exposure), and 795 female-to-male (FtM) subjects receiving testosterone (15,974 total years of exposure). RESULTS: Among MtF individuals one case was encountered, as well as a probable but not proven second case. The estimated rate of 4.1 per 100,000 person-years (95% confidence interval [CI]: 0.8-13.0) was lower than expected if these two cases are regarded as female breast cancer, but within expectations if viewed as male breast cancer. In FtM subjects, who were younger and had shorter exposure to cross-sex hormones compared with the MtF group, one breast cancer case occurred. This translated into a rate of 5.9 per 100,000 person-years (95% CI: 0.5-27.4), again lower than expected for female breast cancer but within expected norms for male breast cancer. CONCLUSIONS: The number of people studied and duration of hormone exposure are limited but it would appear that cross-sex hormone administration does not increase the risk of breast cancer development, in either MtF or FtM transsexual individuals. Breast carcinoma incidences in both groups are comparable to male breast cancers. Cross-sex hormone treatment of transsexual subjects does not seem to be associated with an increased risk of malignant breast development.

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