Prevalence of gender nonconformity in Flanders, Belgium

Gender nonconformity refers to the extent to which a person’s gender identity, gender role and/or gender expression differs from the cultural norms prescribed for people of a particular sex, within a certain society and era. Most data on gender nonconformity focus on the prevalence of gender dysphoria (which also includes a distress factor) or on the number of legal sex changes. However, not every gender nonconforming individual experiences distress or applies for treatment. Population-based research on the broad spectrum of gender nonconformity is scarce and more information on the variance outside the gender binary is needed. This study aimed to examine the prevalence of gender incongruence (identifying stronger with the other sex than with the sex assigned at birth) and gender ambivalence (identifying equally with the other sex as with the sex assigned at birth) based on two population-based surveys, one of 1,832 Flemish persons and one of 2,472 sexual minority individuals in Flanders. In the general population, gender ambivalence was present in 2.2% of male and 1.9% of female participants, whereas gender incongruence was found in 0.7% of men and 0.6% of women. In sexual minority individuals, the prevalence of gender ambivalence and gender incongruence was 1.8% and 0.9% in men and 4.1% and 2.1% in women, respectively. With a current Flemish population of about 6 million, our results indicate a total of between 17,150 and 17,665 gender incongruent men and between 14,473 and 15,221 gender incongruent women in Flanders

Bone size and bone strength are increased in obese male adolescents

Context: Controversy exists on the effect of obesity on bone development during puberty. Objective: Our objective was to determine differences in volumetric bone mineral density (vBMD) and bone geometry in male obese adolescents (ObAs) in overlap with changes in bone maturation, muscle mass and force development, and circulating sex steroids and IGF-I. We hypothesized that changes in bone parameters are more evident at the weight-bearing site and that changes in serum estradiol are most prominent. Design, Setting, and Participants: We recruited 51 male ObAs (10-19 years) at the entry of a residential weight-loss program and 51 healthy age-matched and 51 bone-age-matched controls. Main Outcome Measures: vBMD and geometric bone parameters, as well as muscle and fat area were studied at the forearm and lower leg by peripheral quantitative computed tomography. Muscle force was studied by jumping mechanography. Results: In addition to an advanced bone maturation, differences in trabecular bone parameters (higher vBMD and larger trabecular area) and cortical bone geometry (larger cortical area and periosteal and endosteal circumference) were observed in ObAs both at the radius and tibia at different pubertal stages. After matching for bone age, all differences at the tibia, but only the difference in trabecular vBMD at the radius, remained significant. Larger muscle area and higher maximal force were found in ObAs compared with controls, as well as higher circulating free estrogen, but similar free testosterone and IGF-I levels. Conclusions: ObAs have larger and stronger bones at both the forearm and lower leg. The observed differences in bone parameters can be explained by a combination of advanced bone maturation, higher estrogen exposure, and greater mechanical loading resulting from a higher muscle mass and strength

Sex steroids in relation to sexual and skeletal maturation in obese male adolescents

Background: Childhood obesity is associated with an accelerated skeletal maturation. However, data concerning pubertal development and sex steroid levels in obese adolescents are scarce and contrasting. Objectives: To study sex steroids in relation to sexual and skeletal maturation and to serum prostate specific antigen (PSA), as a marker of androgen activity, in obese boys from early to late adolescence. Methods: Ninety obese boys (aged 10-19 y) at the start of a residential obesity treatment program and 90 age-matched controls were studied cross-sectionally. Pubertal status was assessed according to the Tanner method. Skeletal age was determined by an x-ray of the left hand. Morning concentrations of total testosterone (TT) and estradiol (E2) were measured by liquid chromatographytandem mass spectrometry, free T (FT) was measured by equilibrium dialysis, and LH, FSH, SHBG, and PSA were measured by immunoassays. Results: Genital staging was comparable between the obese and nonobese groups, whereas skeletal bone advancement (mean, 1 y) was present in early and midadolescence in the obese males. Although both median SHBG and TT concentrations were significantly (P < .001) lower in obese subjects during mid and late puberty, median FT, LH, FSH, and PSA levels were comparable to those of controls. In contrast, serum E2 concentrations were significantly (P < .001) higher in the obese group at all pubertal stages. Conclusion: Obese boys have lower circulating SHBG and TT, but similar FT concentrations during mid and late puberty in parallel with a normal pubertal progression and serum PSA levels. Our data indicate that in obese boys, serum FT concentration is a better marker of androgen activity than TT. On the other hand, skeletal maturation and E2 were increased from the beginning of puberty, suggesting a significant contribution of hyperestrogenemia in the advancement of skeletal maturation in obese boys

Bone health in trans persons : clinical evaluation and relevance

Trans persons identify as, or desire to be, a member of the opposite gender of their birth gender. In case of gender dysphoria, this incongruence causes discomfort or distress often leading to the choice for hormonal and/or surgical treatment to conform the body to the desired gender. Although this phenomenon is of all time, and is known in many cultures, it has only gained medical interest in the last decades. Due to more media attention and the widespread use of internet, gender clinics are confronted with increasing numbers of applicants. Consequently, this demands more research of treatment protocols in this underserved group. Hormonal treatment in trans persons consists of sex steroid reversal. The principal endogenous sex steroid (i.e. androgen in men and estrogen in women) is suppressed and replaced by the principal sex steroid of the opposite sex. For trans women, who have a male birth sex, this means androgen suppression and estrogen replacement therapy inducing feminization. Trans men, who have a female birth sex, undergo testosterone therapy, inducing masculinization. Research in trans persons may also shed light on the origin of gender differences in the body and the interplay with sex steroids. Boys, for example, develop longer and bigger bones than girls during puberty indicating a crucial role for sex steroids in this process. Body composition changes during puberty too, resulting in more muscle and less fat mass and a different body shape in men versus women by the time of adolescence. Besides both muscle and fat tissue have an influence on bone. A vast body of evidence indeed pointed out that sex steroids are vital for bone acquisition and maintenance. The differential effects of sex steroids on bone health remain however unclear. In particular, their influence on cortical (the hard outer layer of bone) and trabecular (the interior of bone, a network of rod-like and plate-like tissue) bone needs further clarification. The objectives of this thesis are therefore twofold. We aim to describe bone health in trans persons using hormonal and/or surgical therapy. Secondly, cross-sex hormonal therapy (CSH) in trans persons may help to illuminate differential effects of sex steroids on the skeleton and the interplay with body composition. Previous studies on bone health in trans persons are scarce, often small-scaled and hampered by the use of dual x-ray absorptiometry (DXA). The latter imaging technique shows a projection of the bone and results in the measurement of areal bone mineral density (aBMD). We have made use of peripheral quantitative computed tomography (pQCT). This technique adds a third dimension to bone imaging, quantifies volumetric BMD, and allows the differentiation of cortical and trabecular bone. In chapter 1, we provide information on gender dysphoria its treatment options and give an overview of some important gender differences in bone and body composition and the relationship with sex steroids. Known literature on bone and body composition in trans persons is also summarized. Further, we state our research objectives and this chapter ends with the presentation of the study groups and the materials and methods. In the addendum, we present data on the prevalence on gender incongruence in Flanders in a population-based survey. In chapter 2, we focus on bone geometry, trabecular and cortical vBMD and the relation to body composition in trans persons. We compare bone, lean and fat mass in trans persons prior to any hormonal treatment and control populations (ch2.1) and evaluate short-term (up to 2 years follow-up)(ch 2.2) and long-term effects (ch 2.3) of CSH. We show that prior to treatment, trans women have a similar hormonal status, but already had a lower bone and muscle mass vs. control males and a male reference population (ch 2.1). Osteoporosis is prevalent in 16% of trans women vs. 4% of controls. Peripheral QCT reveale a thinner bone cortex with a lower cortical bone area in trans women compared with control men. We hypothesize that trans women, prior to any hormonal treatment, have a different lifestyle than control men as they have a higher prevalence of 25(OH)vitamin D deficiency (67% vs. 35%) and lower levels of sports activity and muscle mass vs. control men. During the first two years of antiandrogen and estrogen therapy in trans women, the aBMD increases at nearly all measured sites (whole body, lumbar spine, femoral neck, radius) and vBMD and bone geometry is unaffected (ch 2.2.1). Considerable loss of muscle mass and strength is also noted in trans women during CSH, whereas they gain body fat mass and subcutaneous fat mass (appendicular as well as at the hips). In a subgroup of these trans women, antiandrogens are used in monotherapy for a short term (median 25 weeks), before combination with estrogen therapy. The aBMD changes are similar in both groups. The markers of bone turnover increase during the first year, followed by a decrease in the second year in the group that had antiandrogens alone. In the group that used combination therapy from the start, bone turnover markers decline during the first and second year. We conclude that estrogen therapy is able to maintain bone health despite hypoandrogenism and substantial muscle loss. In addition, we propose that estrogen treatment in trans women induces a lower bone turnover leading to an increase in aBMD (by estrogen-mediated filling of the remodeling space). The absence of changes in volumetric bone parameters may have been due to the short follow-up, the relatively low sample size and the higher coefficient of variation of pQCT vs. DXA. In chapter 2.2.2, trans men prior to testosterone treatment and age-matched control women are followed prospectively and after one year. After the baseline visit, trans men received testosterone treatment (testosterone undecanoate 1000mg, IM, 1x/12 weeks), sometimes preceded by progestagens. At baseline, bone parameters are alike in both groups. After one year of testosterone therapy in trans men, considerable increases in muscle mass and strength and markers of bone turnover, and declines in fat parameters (subcutaneous as well as trunk and total body fat mass) are observed. We report a modestly increased aBMD at the total hip and trabecular vBMD in trans men, but not in control women. Other areal and volumetric bone parameters are unaffected. In chapter 2.3.1, we consider the long-term effects of testosterone treatment and sex reassignment surgery (including gonadectomy) on bone and body composition in 50 trans men and 50 age-matched control women in a cross-sectional study. Corresponding with the short-term effects of testosterone therapy, trans men still have higher muscle mass and strength and lower body fat mass vs. control women median 10yr after the start of testosterone therapy. Trans men have a larger waist circumference too, indicating a more central, masculine pattern of fat distribution (apple-shape). A greater cortical bone size at the radius in trans men vs. control women is observed which was related to the higher muscle mass and strength. Trabecular vBMD is also higher than control women, similarly to the increased trabecular vBMD in our short-term study in trans men. Both findings may be suggestive for a direct or indirect (through muscle mass and strength) anabolic effect of testosterone therapy on trabecular and cortical bone. In chapter 2.3.2, in a subgroup of these 50 trans men on long-term testosterone treatment who underwent phalloplasty (n=44), we assess bone health at the forearm that is used as donor-site for radial forearm phalloplasty. We observe no functional limitations on daily life activities, a painless and rather aesthetic scar and unaffected bone health. Long-term effects of CSH on bone geometry and body composition in trans women were previously described by our research group and are therefore not part of this thesis. In chapter 3, body composition is assessed in relationship to cardiovascular factors in 40 trans women and 20 trans men prior to and after one year of CSH. Trans women gain fat and loose muscle and body lean mass, while trans men undergo changes in the opposite direction during the first year of CSH. Estrogen treatment in trans women result in modestly increased insulin resistance and generally improved lipid profile (decline in triglycerides (TG), apolipoprotein (Apo) A and B, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol (TC)) after one year. In contrast, trans men develop less insulin resistance but a worsening of lipid profile (increased TG, LDL and ApoB and lower HDL) in their first year using testosterone treatment. Less decline (in trans men) and a greater incline (in trans women) in fat mass are associated with a less favorable lipid profile. So, the CSH-mediated changes in body composition in trans persons have implications for their cardiovascular profile. In chapter 4, we summarize and discuss the main findings of the included studies. We then highlight the limitations of our work, suggest perspectives for further research and end with a discussion of the clinical relevance of this thesis

Bone in trans persons

Purpose of review : We provide an update of bone health in trans persons on cross-sex hormonal therapy. This drastic hormonal reversal will have direct but also indirect effects on bone, through body composition changes. Recent findings : Recent evidence suggests that trans women, even before the start of any hormonal intervention, already have a lower bone mass, a higher frequency of osteoporosis, and a smaller bone size vs. natal men. During cross-sex hormonal treatment, bone mass was maintained or gained in trans women. In trans men, bone metabolism seemed to increase during short-term testosterone therapy, but no major changes have been found in bone density. On long-term testosterone therapy, larger cortical bone size was observed in trans men vs. natal women. Summary : Follow-up of bone health and osteoporosis prevention in trans persons is important. We advise active assessment of osteoporosis risk factors including the (previous) use of hormonal therapy. Based on this risk profile and the intended therapy, bone densitometry may be indicated. Long-term use of antiandrogens or gonadotropin-releasing hormone agonists alone should be monitored as trans women may have low bone mass, even prior to treatment. Therapy compliance with the cross-sex hormones is of major concern, especially after gonadectomy. Large-scaled, multicenter, and long-term research is needed to determine a well tolerated dosage of cross-sex hormonal treatment, also in elderly trans persons

Transgenderism and reproduction

Purpose of review: The development of new reproductive medicine techniques creates opportunities for preserving fertility in transgender persons. Before, losing fertility was accepted as the price to pay for transitioning. Recent findings: The desire for children is present in many trans persons, as in the general population. Ethical concerns are sometimes raised against the preservation of fertility; however, the only unique aspect of this group is the gender transition of one of the parents. All other elements such as same sex parenthood, use of donor gametes, social stigma, etc., can be found in other groups of parents. Not all reproductive options for all trans persons are equal because not only the gametes are of importance, but also the sex of the (future) partner. In trans women, the best option to preserve gametes is cryopreservation of sperm by preference initiated before starting hormonal therapy. In trans men, donor sperm is most often used, but in theory, there are three options available to preserve fertility: oocyte banking, embryo banking and banking of ovarian tissue. Summary: Fertility is possible for both trans men and women, but it requires timely cryopreservation of gametes or stopping cross-sex hormones and possible fertility treatments which are costly and may be unpleasant. Centers should elucidate their policy and inform trans persons on the possibilities and limitations