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Van Caenegem, K. Wierckx, Y. Taes, D. Dedecker, F. Van de Peer, K. Toye, J. Kaufman, G. 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. The objective of the study was to examine the effects of cross-gender sex steroid exposure on volumetric bone parameters in transsexual men.

Fifty transsexual men after sex reasment surgery with 50 age-matched control women and an additional 16 transsexual men before testosterone substitution and sex reasment surgery with 16 control women participated in the study.

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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 absorptiometrysex steroids, markers of bone turnover and grip strength. Before hormonal treatment, transsexual men had similar body composition and bone geometry as female controls.

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. Sex steroids are important determinants of bone acquisition during puberty and bone homeostasis in adulthood. During puberty, men develop a larger bone mass and size than women 12. Indeed, testosterone stimulates the process of periosteal apposition, causing a greater cortical bone size in men 3whereas pubertal girls experience less periosteal expansion and more endocortical apposition compared with boys 4 Shemale n girl, 5.

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As female-to-male transsexual persons will be referred to as transsexual men undergo ovariectomy and follow life-long testosterone substitution therapy, studies on bone geometry and body composition allow studying sex steroid actions on bone physiology in adults. studies in transsexual men demonstrated that during the first 2 yr of cross-sex hormonal therapy, androgen administration could prevent possible bone loss due to estrogen deficiency 6 — 8. Areal bone mineral density aBMD was higher at cortical sites 89and a histomorphometric study showed a ificantly larger cortical thickness in transsexual men compared with controls Evaluations after a longer exposure time respectively 7.

However, a decline in aBMD after a median of 45 months of cross-sex hormonal therapy was reported, possibly due to inadequate substitution therapy because there was an inverse correlation between LH or FSH and aBMD Mechanical loading and physical activity play an important stimulatory role on the skeleton and were found to be associated with a larger Shemale n girl thickness 212 In transsexual men, the mechanical loading on bone increases through the higher muscle mass, induced by androgens All studies on bone mass in transsexual men were conducted using dual-energy x-ray absorptiometry DXAwhich has limitations in assessing bone geometry.

Due to the two-dimensional view, bone mineral density of larger bones can be overestimated 1 Peripheral quantitative computed tomography can evaluate accurately the volumetric bone mineral density vBMD and differentiate trabecular from cortical bone. In this study, we assessed volumetric bone parameters and body composition in relation to sex steroids and muscle strength in a population of transsexual men before and after a long period of cross-sex hormonal therapy, compared with age-matched healthy control women. All transsexual participants were diagnosed with gender identity disorder Diagnostic and Statistical Manual of Mental Disorders -IV, Every patient was treated following the World Professional Association for Transgender Health standards of care Shemale n girl Fifty transsexual men, will be referred to as the treatment group and used testosterone substitution therapy and had undergone sex reasment surgery SRS; hysterectomy, ovariectomy, and mastectomy before inclusion in this study.

On average, these patients were 8.

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One participant used both oral testosterone undecanoate 40 mg one daily and testosterone gel 50 mg per 5 g, 50 mg daily. The type of treatment testosterone esters IM, testosterone undecanoate IM, or transdermal testosterone gel was not associated with serum testosterone or LH levels or with body composition or bone parameters.

Almost all the participants were Caucasian 48 Belgians and one Dutchand one participant was Iranian. Additionally, 16 Belgian transsexual men, who will be referred to as the untreated group, were recruited in the diagnostic phase and just before the start of cross-sex hormonal therapy and thus before SRS. Gynecological history and fractures were registered. In the treatment group, a history of menstrual irregularities and polycystic ovary syndrome PCOS was found to be unreliable due Shemale n girl the long-time course and hysterectomy and ovariectomy. In the untreated group, one transsexual man had PCOS.

None of the control women had PCOS. In the untreated group, cerebral palsy was present in one participant who did have an active lifestyle and two participants had an episode of eating disorder in the past. After exclusion of these patients and their age-matched controls, the presented did not change substantially.

After exclusion of these women and their matched transsexual men, remained the same. Body weight and anthropometrics were measured in light indoor clothing without shoes. Standing height was measured using a wall-mounted Harpenden stadiometer Holtain, Ltd. The maximum strength of three attempts was assumed to best reflect the current status and history of their musculoskeletal adaptation and was expressed in kilograms.

Procedure details were as described ly Descriptives are expressed as mean and sd or median first to third quartile when criteria for normal distribution were not fulfilled. Comparison of general, anthropometric, biochemical, and hormonal determinations between groups were made with an independent t test or Mann-Whitney U test when variables were not normally distributed Tables 1 and 2.

Multiple regression analysis was used to compare bone and body composition in transsexual men of the treatment group compared with controls Tables 3 4 — 5 and used models included height, weight, and a grouping variable transsexual or control group Shemale n girl independents. The P value of this grouping variable is shown, similarly to other publications of our group Descriptives of general and anthropometric determinations in transsexual men before start of cross-gender hormonal treatment and sex reasment surgery.

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Variables were compared between groups using independent t tests or Mann-Whitney U test when not normally distributed. Descriptives of general, anthropometric, hormonal, and biochemical determinations of transsexual men on long-term cross-gender hormonal treatment and after sex reasment surgery.

To convert nanograms per liter to picomoles per liter for estradiol, multiply by 3. Descriptives of measures of body composition of transsexual men on long-term cross-gender hormonal treatment and after sex reasment surgery. All variables were corrected for weight and height.

Descriptives of bone parameters as measured by DXA at the lumbar spine and left hip of transsexual men on long-term cross-gender hormonal treatment and after sex reasment surgery. Descriptives volumetric bone parameters as measured by pQCT at the distal Shemale n girl parameters and proximal proximal radius and proximal tibia cortical parameters of transsexual men on long-term cross-gender hormonal treatment and after sex reasment surgery.

Logarithmic transformation was used when variables were not normally distributed. We evaluated sex steroids, muscle strength, physical activity, bone turnover markers, and smoking in relation to body composition and volumetric bone parameters in the treatment group and controls using separate multiple regression models.

Independent variables in this model were age, height, weight, treatment whether one had used testosterone substitution or notand the grouping variable transsexual person or notand outcome variables were volumetric bone parameters.

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Control women were taller than transsexual men of this untreated group. No ificant differences in body composition were found in the untreated group compared with controls, and bone parameters measured by DXA were comparable with female controls comparable with the exception of lumbar spine area mean Age, body weight, height, and BMI were comparable between transsexual men and control women Table 2.

There were more smokers in this group compared with controls, and the mean amount of pack-years was ificantly higher.

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As expected, the treatment group had a markedly higher serum testosterone and a lower SHBG and Shemale n girl levels than females, within normal ranges for healthy men Table 2. Hematocrit, creatinine, and total cholesterol levels were all ificantly higher in the treatment group vs. In transsexual men on testosterone substitution, a different body composition with a ificantly larger waist and smaller hip circumference and a higher waist-hip ratio than the female group was found Table 3.

Moreover, this group showed a greater muscle cross-sectional area CSA and a lower fat CSA, reflecting subcutaneous fat, at both the forearm and lower leg vs. Transsexual men on testosterone substitution therapy also demonstrated a ificantly higher grip strength compared with the control subjects Table 2whereas in the untreated transsexual men, no difference in grip strength was observed Table 1. No ificant differences were found in aBMD in the treatment group compared with age-matched control women Table 4. A ificantly higher BMC and bone area of total hip and bone area at the femoral neck were observed in the treatment group compared with the female controls.

At trabecular sites distal radiusthe treatment group scored ificantly higher on vBMD, whereas trabecular area was similar Table 5. There was also a trend toward higher cortical bone area in the treatment group at the proximal tibia. Furthermore, at both cortical sites proximal radius and tibiaa lower cortical vBMD was observed in the treatment group compared with the female controls Table 5 and Fig.

Cortical bone parameters at the radius. Bars represent mean and whiskers 1 sem. Before treatment, no differences in bone parameters between groups were observed in this model Fig. All analyses were adjusted for age, body weight, and height, and no unadjusted associations were determined. No interactions between testosterone and the level of physical activity level were observed in these models data not shown. The length of time on cross-sex hormonal therapy was not associated with volumetric bone parameters or body composition. We found that transsexual men, after long-term treatment with testosterone substitution therapy and SRS, had a different body composition with more muscle mass and strength and less fat mass as well as larger bones and lower vBMD compared with age-matched female subjects.

To evaluate whether these differences could already be present at baseline, we additionally recruited 16 transsexual men before the start of hormonal therapy and SRS. They had similar bone and body composition compared with an age-matched female control group. To our knowledge, this is the first study to report data on volumetric bone parameters in a sizable group of transsexual men, by use of pQCT.

This technique, which is more discriminative than DXA, reveals an increased trabecular vBMD, whereas cortical bone sites are characterized by decreased vBMD and larger endosteal and periosteal bone circumferences in transsexual men on cross-gender hormonal therapy. Thus, these findings indicate that exposure of adult bones to cross-gender hormonal treatment has a ificant impact not only on lean and fat mass but also on the adult skeleton.

The expected anabolic effect of testosterone administration on muscle mass is clearly reflected in our data. Although a direct relationship of testosterone with muscle mass or strength was not found, we did observe an independent negative association of lower serum LH with higher total and regional muscle mass of the treatment group, indicating a dose effect relationship between testosterone treatment and gain in muscle mass.

The lack of associations with serum testosterone is not unexpected. Considering the differences in types of testosterone administration, the variable timing of sampling in relation to the Shemale n girl testosterone dosing, the pharmacokinetic profile, and the single-point testosterone levels in these men, the measured serum testosterone cannot be expected to reliably reflect testosterone exposure.

The demonstrated lower total and subcutaneous fat mass together with the smaller hip and larger waist circumference in the treatment group of transsexual men are indicative for a more central fat distribution. These findings are consistent with studies that showed an android pattern of fat distribution in transsexual men after cross-sex hormonal therapy Shemale n girl In fact, men have on average more visceral fat than women Elbers et al.

After 3 yr of follow-up, the decrease in subcutaneous fat was no longer ificant, but the increase in visceral fat remained important Concordant with this finding, the android pattern of fat distribution is also found in women with hyperandrogenism PCOS 2122 and postmenopausal women undergoing estrogen-testosterone hormonal substitution therapy 23 — The total cholesterol is higher in transsexual men compared with the control women because of the effects of testosterone.

Together with the central pattern of fat distribution, this might mean that the transsexual men have a less favorable metabolic profile compared with the control women. Our demonstrated the presence of a higher trabecular vBMD in transsexual men on cross-sex hormonal treatment compared with age-matched women.

First, the androgen-induced increased muscle mass and strength appeared to be strong positive predictors of trabecular bone parameters independent of weight and height. This is in line with earlier reports on the positive association of grip strength with trabecular vBMD at forearm sites A second explanation may be found in the altered trabecular microstructure in the treatment group. In their study with high-resolution pQCT, Khosla et al.

Supraphysiological doses of testosterone in transsexual men could induce greater trabecular thickness by interaction with the IGF-I axis. Third, the exogenously administered testosterone may exert a dual favorable action on trabecular bone 29 with a direct effect mediated through the androgen receptor, whereas aromatization to estrogens could contribute to maintenance of trabecular bone despite endogenous estrogen deprivation due to ovariectomy, although no associations between estradiol and trabecular bone parameters were found.

The observed higher trabecular vBMD in the treatment group of transsexual men does not confirm of a histomorphometric study that found similar trabecular bone structure in transsexual men vs. The current DXA confirm earlier reports stating maintained aBMD after cross-sex hormonal therapy in transsexual men. The higher bone area but similar aBMD at the femoral neck and total hip in the treatment group compared with controls are in partial agreement with studies, describing an increased aBMD at cortical sites.

An increase in aBMD at the femoral neck was observed in 15 transsexual men after a follow-up of 2 yr of testosterone administration 8 and at the whole body and tibia in a cross-sectional study with 15 transsexual men Shemale n girl median duration of 7. The present findings show that unchanged aBMD in transsexual men is a possibly the result of decreased cortical vBMD and increased bone size. Several explanations for the observed differences in cortical vBMD and bone size in transsexual males in the treatment group vs.

Mechanical loading, through muscle mass and strength, proved to be an independent predictor of volumetric cortical bone parameters and cortical bone size. Mechanical loading can trigger periosteal apposition mechanostat theorywhich could explain the larger periosteal circumference 13 As ly observed in a group of young healthy men, SHBG was positively associated with bone size

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