Katrien Wierckx

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

INTRODUCTION Long-term effects and side effects of cross-sex hormone treatment in transsexual persons are not well known. AIM The aim of this study is to describe the effects and side effects of cross-sex hormone therapy in both transsexual men and women. MAIN OUTCOME MEASURES 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. METHODS Single center cross-sectional study in 100 transsexual persons post-sex reassignment surgery and on average 10 years on cross-sex hormone therapy. RESULTS 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. CONCLUSION 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.

Quality of Life and Sexual Health after Sex Reassignment Surgery in Transsexual Men

INTRODUCTION Although sexual health after genital surgery is an important outcome factor for many transsexual persons, little attention has been attributed to this subject. AIMS To provide data on quality of life and sexual health after sex reassignment surgery (SRS) in transsexual men. METHODS A single-center, cross-sectional study in 49 transsexual men (mean age 37 years) after long-term testosterone therapy and on average 8 years after SRS. Ninety-four percent of the participants had phalloplasty. MAIN OUTCOME MEASURES Self-reported physical and mental health using the Dutch version of the Short Form-36 Health Survey; sexual functioning before and after SRS using a newly constructed specific questionnaire. RESULTS Compared with a Dutch reference population of community-dwelling men, transsexual men scored well on self-perceived physical and mental health. The majority reported having been sexually active before hormone treatment, with more than a quarter having been vaginally penetrated frequently before starting hormone therapy. There was a tendency toward less vaginal involvement during hormone therapy and before SRS. Most participants reported an increase in frequency of masturbation, sexual arousal, and ability to achieve orgasm after testosterone treatment and SRS. Almost all participants were able to achieve orgasm during masturbation and sexual intercourse, and the majority reported a change in orgasmic feelings toward a more powerful and shorter orgasm. Surgical satisfaction was high, despite a relatively high complication rate. CONCLUSION Results of the current study indicate transsexual men generally have a good quality of life and experience satisfactory sexual function after SRS.

Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case control study

OBJECTIVE This study evaluated the short- and long-term cardiovascular- and cancer-related morbidities during cross-sex hormone therapy in a large sample of trans persons. SUBJECTS AND METHODS A specialist center cross-sectional study compared 214 trans women (male-to-female transsexual persons) and 138 trans men (female-to-male trans persons) with an age- and gender-matched control population (1-3 matching). The participants were on cross-sex hormone therapy for an average of 7.4 years. We assessed physical health and possible treatment-related adverse events using questionnaires. RESULTS Five percent of trans women experienced venous thrombosis and/or pulmonary embolism during hormone therapy. Five of these adverse events occurred during the first year of treatment, while another three occurred during sex reassignment surgery. Trans women experienced more myocardial infarctions than the control women (P=0.001), but a similar proportion compared with control men. The prevalence of cerebrovascular disease (CVD) was higher in trans women than in the control men (P=0.03). The rates of myocardial infarction and CVD in trans men were similar to the control male and female subjects. The prevalence of type 2 diabetes was higher in both trans men and women than in their respective controls, whereas the rates of cancer were similar compared with the control men and women. CONCLUSION Morbidity rate during cross-sex hormone therapy was relatively low, especially in trans men. We observed a higher prevalence of venous thrombosis, myocardial infarction, CVD, and type 2 diabetes in trans women than in the control population. Morbidity rates in trans men and controls were similar, with the exception of the increased prevalence of type 2 diabetes.

Reproductive wish in transsexual men

BACKGROUND Hormonal therapy and sex reassignment surgery (SRS) in transsexual persons lead to an irreversible loss of their reproductive potential. The current and future technologies could create the possibility for female-to-male transsexual persons (transsexual men) to have genetically related children. However, little is known about this topic. The aim of this study is to provide information on the reproductive wishes of transsexual men after SRS. METHODS A self-constructed questionnaire was presented to 50 transsexual men in a single-center study. RESULTS The majority (64%) of transsexual men were currently involved in a relationship. Eleven participants (22.0%) reported having children. For eight participants, their female partner was inseminated with donor sperm, whereas three participants gave birth before hormonal therapy and SRS. At the time of interview, more than half of the participants desired to have children (54%). There were 18 participants (37.5%) who reported that they had considered freezing their germ cells, if this technique would have been available previously. Participants without children at the time of investigation expressed this desire more often than participants with children (χ²; test: P= 0.006). CONCLUSIONS Our data reveal that the majority of transsexual men desire to have children. Therefore, more attention should be paid to this topic during the diagnostic phase of transition and to the consequences for genetic parenthood after starting sex reassignment therapy.

Bone Mass, Bone Geometry, and Body Composition in Female-to-Male Transsexual Persons after Long-Term Cross-Sex Hormonal Therapy

CONTEXT Female-to-male transsexual persons (transsexual men) undergo extreme hormonal changes due to ovariectomy and testosterone substitution, allowing studies on sex steroid effects on bone geometry and physiology in the adult. OBJECTIVE The objective of the study was to examine the effects of cross-gender sex steroid exposure on volumetric bone parameters in transsexual men. DESIGN This was a cross-sectional study. SETTING Participants were recruited from the Center for Sexology and Gender Problems at the Ghent University Hospital (Ghent, Belgium). PARTICIPANTS Fifty transsexual men after sex reassignment surgery with 50 age-matched control women and an additional 16 transsexual men before testosterone substitution and sex reassignment surgery with 16 control women participated in the study. MAIN OUTCOME MEASURES The main outcome measures were areal and volumetric bone parameters using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, body composition (dual-energy X-ray absorptiometry), sex steroids, markers of bone turnover and grip strength. RESULTS Before hormonal treatment, transsexual men had similar body composition and bone geometry as female controls. The transsexual men on long-term testosterone therapy, however, demonstrated a higher lean body mass and muscle mass and a greater grip strength as well as a lower body and subcutaneous fat mass and a larger waist and smaller hip circumference compared with female controls (all P < 0.001). We observed a larger radial cortical bone size (P < 0.001) and lower cortical volumetric bone mineral density at the radius and tibia (P < 0.05) in transsexual men on testosterone therapy. CONCLUSIONS Transsexual men on testosterone substitution therapy present with a different body composition with more muscle mass and strength and less fat mass as well as an altered bone geometry with larger bones compared with female controls.

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

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.

Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern

OBJECTIVE The incidence of heart disease increases with age, but is lower in women than in men up to 75 years. A protective effect of female sex hormones or, alternatively, acceleration in male heart disease by testosterone at younger ages, could explain this sex difference. In contrast with the above, male-to-female transsexual subjects (MtoF) treated with estrogens (+anti-androgens) show more cardiovascular pathology than female-to-male transsexual subjects (FtoM) receiving testosterone. Why MtoF suffer more frequently from cardiovascular disease than females is as yet unclear. The mode of cross-sex hormone treatment may be a factor, and, if so, it may need adaptations. SUBJECTS AND METHODS Studies in transsexual people on the effects of cross-sex hormone treatment on surrogate cardiovascular risks and on clinical endpoints were reviewed. With regard to MtoF, a parallel was sought with men with prostate cancer, undergoing androgen deprivation and estrogen administration. RESULTS Exposure of FtoM to testosterone was not associated with a strong increase in cardiovascular events. Aging and pre-existing cardiovascular pathology contributed to the risk of cardiovascular disease in MtoF. Use of the synthetic biopotent compound ethinyl estradiol in a dose two to four times of oral contraceptives increased cardiovascular risk substantially. The route of administration of estrogens (oral vs transdermal) may have impacted on the risks. CONCLUSION MtoF should not be treated with oral ethinyl estradiol. Transdermal estrogens are probably safer than oral estrogens. Pre-existing cardiovascular risks should be taken into consideration when prescribing and choosing the type of estrogens in cross-sex hormone administration (oral vs transdermal). In addition, risk factors, as they emerge with aging, should be addressed.

Sexual Desire in Trans Persons: Associations with Sex Reassignment Treatment

INTRODUCTION 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. AIM This study aims to explore associations between sex reassignment therapy (SRT) and sexual desire in a large cohort of trans persons. METHODS 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). MAIN OUTCOME MEASURES Questionnaires assessing demographics, medical history, frequency of sexual desire, hypoactive sexual desire disorder (HSDD), and treatment satisfaction. RESULTS 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). CONCLUSION 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.

Sperm freezing in transsexual women.

Gender Identity Disorder (GID) is a condition in which a person experiences discrepancy between the sex assigned atbirth and the gender they identify with. Transsexualism is considered the most extreme form of GID and is characterized by the desire to live and be treated as a member of the opposite gender. The prevalence of male-to-female transsexualism in Belgium is estimated at 1 per 12,900 males (De Cuypere et al., 2007). The treatment consists of cross-sex hormone therapy and sex reassignment surgery in accordance with the Standards of Care of the World Professional Association for Transgender Health (WPATH) (7th Version) (www.wpath.org). At the center in Ghent, male-to-female transsexual persons, denoted as transsexual women, are treated in a multidisciplinary approach, including cross-sex hormone therapy and sex reassignment surgery for most. Hormone therapy with anti-androgens and estrogens is used in the majority of transsexual women. After at least 1 year of hormonal therapy, sex reassignment surgery can be offered, which includes orchidectomy andpenectomy in combinationwith vaginoplasty (Selvaggiet al., 2005).Bothhormonalandsurgical interventionsnegativelyaffect the male reproductive system. Hormonal therapy itself leads to decreased spermatogenesis and eventually to azoospermia (Lubbert, Leo-Rossberg, & Hammerstein, 1992; Schulze, 1988). Currently, it is unknown whether spermatogenesis will restore after prolonged estrogen treatment or not (Hembree et al., 2009). Sex reassignment surgery, on the other hand, results in an irreversible loss of natural reproductive capacity in transsexual women. Current reproductive techniques can offer adult transsexual women the possibility of having genetically related children (De Sutter, 2001). They can store their sperm for long-term cryopreservation before undergoing hormonal therapy for future use in assisted reproductive techniques (ART). Sexual orientation of transsexual women may influence the future plans for using the frozen sperm. If transsexual women have a female partner, they can procure children through intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection, based upon the sperm quality after thawing. Reproductive options for transsexual women with a male partner are more difficult as they need oocyte donation as well as a surrogate mother. Reproductive needs and rights of transsexual persons have already been recognized for over 15 years (Lawrence, Shaffer, Snow, Chase, & Headlam, 1996) and since 2001 the WPATH Standards of Care contains a paragraph that addresses the need to discuss reproductive issues with transsexual persons, prior to starting hormonal treatment (Meyer et al., 2001). Also, the new WPATH Standards of Care (Seventh version) (2011) as well as the Clinical Practice Guidelines of the Endocrine Society (Hembree et al., 2009) clearly state that transsexual persons should be encouraged to consider fertility issues before starting cross-gender hormonal treatment. On the other hand, research on this topic is still scarce. In the past 10 years, only two studies have investigated the opinions of transsexual persons themselves concerning this topic (De Sutter, Kira, Verschoor, & Hotimsky, 2002; Wierckx et al., 2012) and few have addressed reproductive difficulties (e.g., access to ART in transsexual patients) (AlvarezK. Wierckx (&) G. T’Sjoen Department of Endocrinology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium e-mail: Katrien.Wierckx@ugent.be

Long‐Term Evaluation of Donor‐Site Morbidity after Radial Forearm Flap Phalloplasty for Transsexual Men

INTRODUCTION Phalloplasty using the radial forearm flap is currently the most frequently used technique to create the neophallus in transsexual men (formerly described as female-to-male transsexual persons). Although it is considered the gold standard, its main disadvantage is the eventual donor-site morbidity in a young, healthy patient population. AIM The study aims to examine the long-term effects of radial forearm flap phalloplasty in transsexual men and to evaluate aesthetic outcome, scar acceptance, bone health, and daily functioning. MAIN OUTCOME MEASURES Scars were evaluated with the patient and observer scar assessment scale, the Vancouver Scar Scale, and self-reported satisfaction. Bone health was assessed using dual X-ray absorptiometry and peripheral quantitative computed tomography, and daily functioning using a physical activity questionnaire (Baecke). These measurements were compared with 44 age-matched control women. METHODS This is a cross-sectional study of 44 transsexual, a median of 7 years after radial forearm flap phalloplasty, recruited from the Center for Sexology and Gender Problems at the Ghent University Hospital, Belgium. RESULTS We observed no functional limitations on daily life activities, a pain-free and rather aesthetic scar, and unaffected bone health a median of 7 years after radial foreram flap phalloplasty. Over 75% of transsexual men were either satisfied or neutral with the appearance of the scar. CONCLUSIONS Transsexual men, despite scarring the forearm, consider the radial forearm flap phalloplasty as worthwhile.