Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study

Abstract

The aim of this study was to explore the effect of long-term cross-sex hormonal treatment on cortical and trabecular bone mineral density and main biochemical parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F) transsexuals and 15 female-to-male (F-M) transsexuals treated with either an antiandrogen in combination with an estrogen or parenteral testosterone were included in this cross-sectional study. BMD was measured by DXA at distal tibial diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and subregions, and whole body (WB) and Z-scores determined for both the genetic and the phenotypic gender. Biochemical parameters of bone turnover, insulin-like growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F transsexuals were significantly older, taller and heavier than F-M transsexuals. They were treated by cross-sex hormones during a median of 12.5 years before inclusion. As compared with female age-matched controls, they showed a significantly higher median Z-score at TDIA and WB (1.7+/-1.0 and 1.8+/-1.1, P < 0.01) only. Based on the WHO definition, five (who did not comply with cross-sex hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex hormones during a median of 7.6 years. They had significantly higher median Z-scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9+/-0.2 SD, +1.0+/-0.4 SD and +1.4+/-0.3 SD, respectively, P < 0.0001 for all) and reached normal male levels except at TEPI. They had significantly higher testosterone and IGF-1 levels (p < 0.001) than M-F transsexuals. We conclude that in M-F transsexuals, BMD is preserved over a median of 12.5 years under antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is preserved or, at sites rich in cortical bone, is increased to normal male levels under a median of 7.6 years of androgen treatment in this cross sectional study. IGF-1 could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.

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)

“…The latter long-term study also demonstrated higher serum levels of bone resorption markers, which is in agreement with the current results (9). However, not all studies in trans men documented higher bone resorption (11,19,20). Furthermore, our observations on areal bone parameters correspond with previous research reporting a preservation of aBMD during the first years of testosterone treatment (11,12,13,21,22) as well as after a longer exposure time and SRS (up to 10 years) in trans men (19,20,23).…”

Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women

“…In dialysed renal insufficiency patients, earlier research has provided evidence for the preservation of cortical bone (measured at T-DIA) with continuous ambulatory peritoneal dialysis compared to haemodialysis, possibly in relationship with the higher residual renal function observed in the former [18]. Furthermore, in the very specific population of female to male transsexuals under long-term hormonal treatment, the effect of androgens on cortical bone was shown in a crosssectional study measuring BMD at the tibial sites [10]. In idiopathic renal stone formers, BMD was previously shown to be reduced at LS, Ward's triangle, T-EPI and T-DIA, whereby the latter two showed the largest magnitudes of change [19].…”

“…For tibial BMD, the local Bern normative database derived from 400 healthy Caucasian women living in the area of Bern, Switzerland served as reference [10]. Peak bone mass (mean value±SD of the age group 20 to 29 years) in this female reference population is 1.278±0.116 g/cm 2 (T-DIA), and 0.763±0.094 g/cm 2 (T-EPI), respectively.…”

Osteoporosis and male age-related hypogonadism: role of sex steroids on bone (patho)physiology

“…The effects of androgens on cortical bone are better documented, even if not completely defined. Several studies have demonstrated that androgens contribute to periosteal bone accrual in men (78) as well as in male rodents (79) and that androgens induce the differences in bone size between men and women (80). Androgens may act on the periosteal surface by increasing periosteal bone formation.…”

“…Thus the effects of the aromatization of androgens on cortical bone cannot be excluded. In any case, however, some preliminary evidence speaks in favor of a key role for estrogen on cortical bone in men too; several studies have shown a positive correlation between androgens and cortical thickness (10,78,79,81), while the FEI seems not to be associated with cortical bone size in young men during pubertal bone accrual (85). This issue remains poorly understood at the moment and a link to the activity of a-or b-estrogen receptors and their tissue distribution might even be supposed, since periosteal apposition is induced by a-estrogen receptor, while its inhibition is mediated by the b-estrogen receptor (29,46).…”