Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case-controlled study (ENIGI).

PURPOSE: To assess the evolution of body composition and bone metabolism in trans men during the first year of cross-sex hormonal therapy. METHODS: In a prospective controlled study, we included 23 trans men (female-to-male trans persons) and 23 age-matched control women. In both groups, we examined grip strength (hand dynamometer), biochemical markers of bone turnover (C-terminal telopeptides of type 1 collagen (CTX) and procollagen 1 aminoterminal propeptide (P1NP)), total body fat and lean mass, and areal bone mineral density (aBMD) by dual-X-ray absorptiometry (DXA) and fat and muscle area at the forearm and calf, bone geometry, and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), before treatment and after 1 year of treatment with undecanoate (1000 mg i.m./12 weeks). RESULTS: Before hormonal treatment, trans men had similar bone and body composition compared with control women. Testosterone treatment induced in trans men a gain in muscle mass (+10.4%) and strength and loss of fat mass (-9.7%) (all P<0.001) and increased the levels of P1NP and CTX (both P<0.01). Areal and volumetric bone parameters remained largely unchanged apart from a small increase in trabecular vBMD at the distal radius and in BMD at the total hip in trans men (P=0.036 and P=0.001 respectively). None of these changes were observed in the control group. CONCLUSIONS: Short-term testosterone treatment in trans men increased muscle mass and bone turnover. The latter may rather reflect an anabolic effect of testosterone treatment rather than bone loss.

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study.

UNLABELLED: Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton. PURPOSE: The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy. METHODS: In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-ß estradiol 100 µg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily. RESULTS: Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05). CONCLUSIONS: Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Relation of adrenal-derived steroids with bone maturation, mineral density and geometry in healthy prepubertal and early pubertal boys.

BACKGROUND: Little is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys. OBJECTIVE: To study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys. METHODS: 98 healthy prepubertal and early pubertal boys (aged 6-14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand. RESULTS: Adrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD). CONCLUSION: In healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys.

Associations of sex steroids with bone maturation, bone mineral density, bone geometry, and body composition: a cross-sectional study in healthy male adolescents.

BACKGROUND: Although both testosterone (T) and estradiol (E2) are considered essential in the regulation of the male skeleton, there are few data concerning the relative contribution of T and E2 on bone mineral density (BMD), bone geometry, and bone maturation in healthy boys. OBJECTIVE: The objective of the study was to analyze the relationship between T and E2 and BMD, bone geometry, skeletal maturation, and body composition. METHODS: This is a cross-sectional study in 199 healthy boys (aged 6-19 y). T and E2 were determined by liquid chromatography tandem mass spectrometry. Whole-body and lumbar areal bone mineral density (aBMD) and bone area, lean mass, and fat mass were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) volumetric BMD (vBMD) and bone geometry were assessed at the nondominant forearm and leg using peripheral quantitative computed tomography. Skeletal age was determined by an X-ray of the left hand. RESULTS: T was positively associated with lean mass (P < .001), lumbar and whole-body bone area (P < .001), trabecular and cortical area (P < .01), and periosteal circumference (P < .01) at the radius. E2 was positively associated with lumbar and whole-body aBMD (P < .001), trabecular vBMD at the radius and tibia (P < .01), and cortical thickness at the radius (P < .05). E2 was an independent negative predictor of the endosteal circumference (P < .01). Moreover, E2 was positively associated with bone age advancement (P < .001). CONCLUSION: Circulating E2 is positively associated with bone maturation and aBMD and vBMD and negatively with endosteal circumference in healthy boys, whereas T is a determinant of lean mass and bone size. These findings underscore the important role of E2 in skeletal development in boys.

Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy.

OBJECTIVE: Cross-sex hormonal therapy and sex reassignment surgery (including gonadectomy) in transsexual persons has an impact on body composition and bone mass and size. However, it is not clear whether baseline differences in bone and body composition between transsexual persons and controls before cross-sex hormonal therapy play a role. DESIGN: A cross-sectional study with 25 male-to-female transsexual persons (transsexual women) before cross-gender sex steroid exposure (median age 30 years) in comparison with 25 age-matched control men and a male reference population of 941 men. MAIN OUTCOME MEASURES: Areal and volumetric bone parameters using respectively dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), body composition (DXA), grip strength (hand dynamometer), Baecke physical activity questionnaire, serum testosterone and 25-OH vitamin D. RESULTS: Transsexual women before cross-sex hormonal therapy presented with less muscle mass (p≤0.001) and strength (p≤0.05) and a higher prevalence of osteoporosis (16%) with a lower aBMD at the hip, femoral neck, total body (all p<0.001) and lumbar spine (p=0.064) compared with control men. A thinner radial cortex (p≤0.01) and lower cortical area at the radius and tibia (both p<0.05) was found in transsexual women vs. control men. Serum testosterone was comparable in all 3 groups, but 25-OH vitamin D was lower in transsexual women (p≤0.001). CONCLUSIONS: Transsexual women before the start of hormonal therapy appear to have lower muscle mass and strength and lower bone mass compared with control men. These baseline differences in bone mass might be related to a less active lifestyle.

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.

Inverse association between bone turnover rate and bone mineral density in community-dwelling men >70 years of age: no major role of sex steroid status.

Bone loss is accelerated in elderly men. Little is known about the pathophysiology of senile bone loss or about the role played by relative sex steroid deficiency in the determination of bone turnover in elderly men. In a population-based sample of 283 healthy, ambulatory men, aged 71-86 years, we sought to determine whether lower bone mineral density (BMD; using dual-energy X ray absorptiometry at the hip and the forearm) is associated with higher bone turnover, and we assessed the impact of sex steroid status on bone turnover. Indices of bone formation, serum osteocalcin (s-Oc), and bone-specific alkaline phosphatase (s-bAP) and indices of bone resorption, serum and urinary telopeptide of type I collagen (s-CTx and u-CTx), and urinary free deoxypyridinoline (u-Dpd) were intercorrelated (r = 0.29-0.76, p < 0.001). Bone turnover indices were negatively associated with BMD (r = -0.17 to -0.34, p < 0.01). In univariate analyses, there was a trend toward weak negative associations of bone turnover markers with serum free testosterone (FT), significant only for s-Oc and s-CTx (r = -0.16 and -0.14, p < 0.01), and with serum free estradiol (FE(2)), significant only for u-CTx and s-CTx (r = -0.18 and -0.19; p < 0.01). The lower quartile for FE(2) was associated with higher values of u-CTx (p = 0.003) and s-CTx (p < 0.001). However, in multivariate models, for the individual markers of bone turnover a negative association between estradiol (E(2)) or FE(2) and s-CTx was the only remaining (marginally) significant association (p < 0.05) for the relationship between sex steroids and any of the bone turnover indices assessed. In community-dwelling men age >70 years, bone turnover rate, as determined by biochemical markers, is a significant negative determinant of prevalent BMD. However, the findings do not support the view that relative differences in sex steroid status, as observed among healthy elderly men, have a major impact on bone turnover.

Limited clinical utility of a self-evaluating risk assessment scale for postmenopausal osteoporosis: lack of predictive value of lifestyle-related factors.

The aim of this study was to assess the efficiency of a self-administered questionnaire to identify subjects with postmenopausal osteoporosis in the setting of first line medical care. A sample of 300 postmenopausal women completed the questionnaire based on 18 items. Bone mineral density at the lumbar spine (BMD-L), total hip (BMD-H), and femoral neck (BMD-N) was used as objective criterion for evaluation. The mean risk score was 8.2 +/- 3.21. BMD was correlated with total risk score: r = -0.32 for BMD-L, -0.36 for BMD-N, and -0.43 for BMD-H. Cutoff points for the risk score (equal likelihood points) according to a T-score threshold of -2.5 were 8.6 for BMD-L and BMD-N and 9.3 for BMD-H; specificity and sensitivity was 62% and 62%, respectively, for BMD-L, 65% and 62% for BMD-N, and 75% and 63% for BMD-H. Stepwise multiple regression analysis of the questionnaire items in relation to BMD showed higher correlation coefficients for models including individual items rather than the overall risk score. Items concerning low weight, older age, and wrist fracture after 50 years of age were always selected as significant determinants of BMD (R = 0.43-0.55). Hormonal replacement therapy was also an important determinant. Lifestyle-related items did not contribute significantly. In conclusion, the diagnostic performance of the 18-item self-administered questionnaire was poorer than a shortened questionnaire omitting lifestyle factors. The clinical utility of a questionnaire should ultimately be evaluated in the specific optic of a chosen global strategy for prevention of osteoporotic fractures.