Abstract
Objectives:
Transgender individuals submitted to hormone or surgical treatment may have alterations in their bone metabolism as these elements are important players in bone remodeling. We aimed to study bone mineral density (BMD) and body composition in transwomen undergoing cross-sex hormonal treatment (CSHT) from Brazil for over 3 years, comparing them with female and male controls.
Methods:
93 individuals (31 transwomen, 31 females and 31 males paired for age and body mass index) were studied for bone mass, and body composition by densitometry (by DXA). Epidemiological and clinical data were collected through direct questioning.
Results:
Low bone mass (T score ≤2) was found in 12.9% of transwomen; in 3.2% of females and 3.3% of males. Transwomen individuals had lower spine Z score (0.26 ± 1.42 vs 0.50 ± 1.19) and femur Z score (−0.41 ± 0.95 vs 0.29 ± 1.04) than females. They had lower total femur Z score than males (−0.41 ± 0.95 vs 0.20 ± 0.83). Lean mass values correlated positively with total femur BMD (ρ = 0.40; 95% confidence interval = 0.009–0.68; p = 0.04) and BMD in femoral neck (ρ = 0.48; 95% confidence interval = 0.11–0.74; p = 0.01) but neither the type of therapy received nor the time that they were used, impacted bone mass.
Conclusion:
Low BMD is found frequently in transwomen and it is correlated with lean body mass.
Advances in knowledge:
There are few studies of the effects of hormone therapy on the bones and muscles of transwomen. This study demonstrated that significant changes occur, and that the population studied needs greater care in musculoskeletal health.
Introduction
Estrogens play a crucial role in the bone metabolism of males and females. A cross-sex hormonal and surgical treatment for sexual reassignment with exogenous estrogens or anti-androgens, may influence bone mass and body mass composition interfering in the risk of osteoporosis and low impact fractures.1–3 Some authors have found an increase in spine bone mineral density (BMD) in transwomen,4 while Lapauw et al3 have shown that this group of individuals has less lean mass, less muscle strength, and BMD when compared to controls. Another study2 with 25 transwomen showed that this population has lower BMD compared to control males even before beginning hormonal treatment. High percentage of smokers3 and low level of sports-related physical activity in this group of individuals are given as possible explanations.2,3 Until present, it is unknown if the Z score in a BMD of a transgender individual should be done according to the affirmed gender or birth determinate sex. Actually, there are few studies on the action of female steroids on male bones. The results are contradictory with different methodologies and small samples. In addition, some authors demonstrated preservation and even bone mass gain and other studies showed bone mass loss.3,5–7
Lean mass and fat mass correlate with BMD as demonstrated by a larger number of studies, with positive action of lean mass on BMD in relation to fat mass. Regardless of BMD, lean mass has been considered one of the risk factors of fracture amongst the elderly. Regarding fat mass, obese adults have higher BMD, thicker and denser cortices, and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest that obesity may protect against age-related bone loss and may increase peak bone mass.8–10
In addition, BMD is a multifactorial characteristic influenced by life habits and genetic.
Data on BMD of transwomen from Brazil are presented comparing them with both male and female controls.
Methods and materials
Study population
This is a cross-sectional study approved by the local Committee of Ethics in Research. All participants agreed to participate in the study and signed consent.
A total of 321 transwomen were selected from those attended at the Centro de Pesquisa e Atendimento a Travestis e Transexuais, from August 1, 2018 to August 20, 2019, in Curitiba, Paraná, Brazil. The inclusion criteria used in this study were: Brazilian transwomen, aged 25–35 years and using CSHT for a minimum of 3 years. It is known that it is up until the age of 25 that the maximum peak of BMDy is reached and from 35 years, the loss of BMD can occur naturally.11
These exclusion criteria were used: a carrier of chronic diseases and/or the continuous use of medicines that alter bone metabolism. After evaluation of the inclusion and exclusion criteria, 46 were selected. Among these, 31 agreed to participate in the study.
Two paired control groups (one of cis-females and one of cis-males) were selected with the same number of participants, which were carefully chosen according to inclusion, exclusion, body mass index (BMI) and lifestyle (physical activity, alcohol use and smoking). (Table 1).
Table 1.
Pairing data in the sample of transsexuals, females and males
| Transsexuals N = 31 |
Females N = 31 |
P (*) | Males N = 31 |
P (**) | ||
|---|---|---|---|---|---|---|
|
Median age (years) (IQR) |
29 (27-31) |
30 (27-37) |
0.20 | 29 (26-32) |
0.71 | |
|
Median BMI (kg/m2) (IQR) |
25.7 (22.3–30.0) |
27.8 (23.5–29.5) |
0.31 | 26.2 (23.4–30.8) |
0.68 | |
| Ethnic background (auto declared)- n (%) | ||||||
| Caucasians | 28 (90.3) | 27 (87.0) | 0.36 | 28 (93.3) | 0.37 | |
| Afro descendants | 0 | 2 (6.4) | 1 (3.3) | |||
| Others | 3 (9.6%) | 2 (6.4) | 1 (3.3) | |||
| Smokers n (%) | 7 (22.5) | 3 (9.6) | 0.30 | 4 (13.3) | 0.50 | |
| Use of alcohol (Yes/No) | 15/16 | 19/12 | 0.30 | 9/21 | 0.14 | |
| Use of antidepressants | 3 (9.6) | 2 (6.4) | 1.00 | 0 | 0.23 | |
| Years of formal study n (%) | ||||||
| Until 8 years | 1 (3.2) | 0 | 0.09 | 0 | 0.17 | |
| Until 12 years | 15 (48.3) | 8 (25.8) | 21 (70) | |||
| More than 12 years | 15 (48.3) | 23 (74.1) | 9 (30) | |||
| Exercise | Insufficient | 6 (19.3) | 15 (48.3) | 0.0006 | 16 (53.3) | 0.02 |
| Moderate | 8 (25.8) | 13 (41.9) | 14 (46.4) | |||
| Active | 17 (54.8) | 3 (9.6) | 0 | |||
| Income (number of minimum wage) n (%) | ||||||
| No income | 4 (12.9) | 6 (19.3) | 0.82 | 4 (13.3) | 0.10 | |
| Until 1 | 5 (16.1) | 3 (9.6) | 4 (13.3) | |||
| Until 2 | 9 (29.0) | 9 (29.0) | 17 (56.6) | |||
| three or more | 13 (41.9) | 13 (41.9) | 5 (16.6) | |||
BMI, Body mass index; IQR, interquartile range; n, number.
p-value of transsexuals vs females
p-value of transsexuals vs males
DXA scans
All survey participants performed the BMD and total body composition (TBC) examination at the same place and with the same equipment, using dual energy X-ray absorptiometry, Lunar Prodigy Advance (Encore version 14.10, GE Healthcare, Madison, WI). In the BMD examination, two segments, lumbar spine and femur were evaluated. The lumbar spine was evaluated in the L1–L4 region. The right femur was evaluated in the regions of the total femur and femoral neck. For BMD analysis, the Z-Score was calculated using age-matched controls from the National Health and Nutrition Examination Survey III (NHANES III) study group.12 It was considered as low bone mineral density individuals with Z-Score ≤−2.0 SD for age.13 For transwomen, reference values for cis-males were used; for the female control group reference values for cis-females were used, and for the male control group, reference values for cis-males.
At TBC, total body fat distribution and total lean body mass distribution were evaluated using the index proposed by the Foundation for the National Institutes of Health,14 which is the calculation of sum of appendicular lean mass (arms and legs)/BMI in m2 with cut-off points for low lean mass values <0.789 m2 for males and <0.512 m2 for females and the relative skeletal muscle mass index (RSMI) or Baumgartner classification, which is the calculation of the sum of appendicular lean mass/height2 in kg/m2 with cut-off points for low lean mass values <7.26 kg/m2 for males and <5.45 kg/m2 for females.15 For the evaluation of total body fat mass, the index was used the fat mass index (FMI), which is the calculation of total body fat mass/height2 in kg/m2, with cutoff values between 3 and 6 for males and between 5 and 9 for females.16 Total body composition is the sum of lean mass and fat mass in grams.
CSHT for transwomen is provided free of charge by the public health system to users. In accordance with the protocol used in our ambulatory, transwomen have these options: (a) Estrogens: the first option is oral estradiol valerate at a dose of 1–4 mg/day. As a second option conjugated estrogen, orally, at a dose of 0.625–2.5 mg/day. Patients with a morbid history of thromboembolic events should use estradiol patches with doses ranging from 50 to 200 mcg, changed every 2–3 days. (b) Androgen blockers: preferably Cyproterone, at a dose of 50–100 mg/day. (c) Another option for associated use is Spironolactone, at a dose of 100–200 mg/day.
Statistics
Data distribution were studied with the Shapiro–Wilk Test. Central tendency of parametric data was expressed in media and standard deviation (SD) and of non-parametric data using median values and interquartile range (IQR). To compare nominal data such as pairing data on ethnic background, income, use of alcohol, tobacco and antidepressants, formal education and exercise, the Fisher and χ2 tests was used. To evaluate pairing data on age and BMI of transsexual group with males or females and to study BMI according to hormonal treatment, the Mann–Whitney test and unpaired t-test was used. Comparisons of BMD values and body composition parameters in the tree groups, as well as comparisons of BMI according to periods of treatment duration were done by the ANOVA followed by Dunnet’s Test if data were parametric or by the Kruskall–Wallis test followed by Dunn’s test if non-parametric. Correlation studies of BMD with values of TBC were done by Spearman test. The significance adopted was 5%.
Results
Description of studied sample
The studied sample had 93 individuals (31 transsexuals, 31 female and 31 males) paired according to Table 1.
In the transsexual sample 28/31 (90.3%) were caucasians, 15/31 (48.3%) had more than 12 years of formal study, 17/31 (54.8%) did regular physical activity, 5/31 (16.1%) had a stable conjugal relationship and 26/31 (83.8%) were single, none stated other disease other than depression that was found in 3/31 (9.6%) and 11/31 (35.4%) had familial history of diabetes mellitus.
Regarding treatment of the transsexual sample there was only the use of estrogens (estradiol from 1 to 4 mg/ daily) in 4/31 (12.9%), only anti-androgens (spironolactone and 50–100 mg/daily of cyproterone) in 5/31 (16.1%) and both in 22/31 (70.9%). About 9.6% (3/31) used hormonal treatment for 3 years; 35.4% (11/31) from 4 to 5 years; 35.4% (11/31) from 6 to 10 years and 19.3% (6/31) for more than 10 years.
Description of bone mass in the transsexual sample and study on the effect of type and duration of hormonal treatment on bone mass
The results of bone the mass study in the transgender group showed that the mean value of spine BMD went from 0.843 to 1.512 g/cm2 (mean of 1.187 ± 0.172); the values of total femur BMD went from 0.757 to 1.219 g/cm2 (mean value of 1.032 ± 0.138) and the values of femoral neck from 0.757 to 1.319 g/cm2 (mean values of 1.080 ± 0.179). About 6/31 (19.3%) individuals could not have femoral bone density done due to artifacts (industrial silicone in the gluteal region). The mean bone density in their forearm went from 0.805 to 1.025 g/cm2 (median of −1.400; IQR=−1.600 to −0.350 g/cm2). The Z score in the spine went from −3.10 to +2.40 (mean value of −0.26 ± 1.42); the Z score in the total femur region ranged from – 2.30 to +1.60 (mean of −0.41 ± 0.95), in the neck of femur from −2.10 to 3.60 (mean of −0.06 ± 1.37) and in the forearm from −1.90 to 0.40 (median of −1.40; IQR = −1.60 to 0.35). The frequency of Z score distribution according to the studied region can be seen in Figure 1.
Figure 1.
Distribution of Z score in the transsexual studied sample.
Table 2 shows the results of when individuals using estrogen were compared to those not using and when those using antiandrogen therapy were compared with those not using, with no differences detected. Studies of BMI values according to duration of hormonal treatment is seen in Table 3, with no relationship of BMI with treatment duration found.
Table 2.
Study of bone mass density according to estrogens and anti-androgens use in transwomen (n = 31)
| Transwomen users | Transwomen Not users |
P | |
|---|---|---|---|
| ANTI-ANDROGENS TREATMENT | |||
| Spine (g/cm2) | 1.190 ± 0.175 | 1.165 ± 0.199 | 0.78 |
| Total femur (g/cm2) | 1.024 ± 0.143 | 1.090 ± 0.098 | 0.45 |
| Femoral neck (g/cm2) | 1.081 ± 0.188 | 1.070 ± 0.113 | 0.92 |
| ESTROGEN TREATMENT | |||
| Spine (g/cm2) | 1.185 ± 0.175 | 1.200 ± 0.161 | 0.86 |
| Total femur (g/cm2) | 1.041 ± 0.144 | 0.989 ± 0.115 | 0.50 |
| Femoral neck (g/cm2) | 1.083 ± 0.185 | 1.010 ± 0.143 | 0.40 |
Table 3.
Study of BMI according duration of hormonal treatment
| ≤5 years | 6–10 years | >10 years | P | |
|---|---|---|---|---|
| Mean bone mass density (g/cm2) | ||||
| Spine | 1.174 ± 0.206 | 1.189 ± 0.166 | 1.215 ± 0.08 | 0.88 |
| Femur (total) | 1.040 ± 0.168 | 1.076 ± 0.112 | 0.960 ± 0.093 | 0.31 |
| Femur (neck) | 1.075 ± 0.191 | 1.163 ± 0.191 | 0.978 ± 0.077 | 0.16 |
| Mean Z score | ||||
| Spine | −0.37 ± 1.72 | −0.23 ± 1.39 | −0.03 ± 0.72 | 0.88 |
| Femur (total) | −0.36 ± 1.16 | −0.11 ± 0.78 | −0.90 ± 0.63 | 0.31 |
| Femur (neck) | 0.03 ± 1.42 | 0.67 ± 1.53 | −0.68 ± 0.61 | 0.18 |
BMI, body mass index.
Study of bone mineral density in transwomen in relationship to body composition
The correlation studies of bone mass parameters and body composition of transwomen are on Table 4. It is possible to see the influence of total lean mass and of the relative skeletal muscle mass index lean bone mass distribution in the femur bone mass density.
Table 4.
Correlation studies of body composition with bone mineral density in transsexual individuals (n = 31)
| Rho | 95% CI | P | |
|---|---|---|---|
| Total fat (g) | |||
| Spine (g/cm2) | 0.01 | −0.35 to 0.37 | 0.93 |
| Total Femur (g/cm2) | 0.37 | −0.03 to 0.76 | 0.06 |
| Femoral neck (g/cm2) | 0.37 | −0.03 to 0.67 | 0.06 |
| Total lean mass (g) | |||
| Spine (g/cm2) | 0.21 | −0.14 to 0,55 | 0.23 |
| Total femur (g/cm2) | 0.40 | 0.009 to 0.68 | 0.04 |
| Femoral neck (g/cm2) | 0.48 | 0.11 to 0.74 | 0.01 |
| Fat distribution – FMI | |||
| Spine (g/cm2) | −0.0007 | −0.35 to +0.35 | 0.99 |
| Total femur (g/cm2) | 0.38 | −0.01 to 0.67 | 0.05 |
| Femoral neck (g/cm2) | 0.30 | −0.10 to 0.62 | 0.09 |
| Lean mass distribution – RSMI (Kg/m2) | |||
| Spine (g/cm2) | 0.13 | −0.22 to +0.47 | 0.45 |
| Total femur (g/cm2) | 0.49 | 0.13 to 0.74 | 0.01 |
| Femoral neck (g/cm2) | 0.49 | 0.12 to 0.74 | 0.01 |
| Lean mass distribution – FNHI index | |||
| Spine (g/cm2) | 0.08 | −0.28 to +0.42 | 0.66 |
| Total femur (g/cm2) | 0.04 | −0.35 to 0.43 | 0.83 |
| Femoral neck (g/cm2) | 0.04 | −0.35 to +0.42 | 0.83 |
FMI, fat mass index; FNIH, Foundation for the National Institute of Health; RSMI, relative skeletal muscle mass index.
Comparison of bone mineral density and body composition of transwomen with cis-females and cis-males.
In the studied sample, 4/31 (12.9%) of transwomen, 1/31 (3.2%) of females and 1/31 (3.2%) males had Z score equal or less than two in at least one measurement. The comparison of BMI of transwomen with male and female controls is on Table 5.
Table 5.
Comparison of bone mass and body composition of transsexuals, females and males
| Bone mass | Transsexuals n = 31 | Females n = 31 | Males n = 31 | P |
|---|---|---|---|---|
| Z score spine | −3.1 to +2.4 Mean = 0.26±1.426 |
−2.2 to +3.1 Mean =+ 0.50±1.19 |
−2.0 to +1.7 Mean =+ 0.13±0.93 |
0.04 (a) |
| BMD Spine (g/cm2) | 0.843 to 1.512 Mean = 1187±0.171 |
0.921 to 1.312 Mean = 1241±0.141 |
0.985 to 1.428 Mean = 1232±0.112 |
0.11 |
| Z score total femur | −2.3 to +1.60 (§) Mean = −0.41±0.95 |
−2.2 to +2.10 Mean=+0.29±1.04 |
−1.9 to +1.8 Mean = 0.20±0.83 |
0.01 (a)(b) |
| BMD total femur (g/cm2) | 0.757 to 1319 (§) Mean = 1032±0.138 |
0.716 to 1142 Mean = 1043±1297 |
0.813 to 1364 Mean = 1109±0.127 |
0.04 (c) |
| Z score femoral neck | −2.10 to +3.6 (§) Mean =+ 0.006±1.37 |
−1.90 to +2.50 Mean =+ 0.19±1.01 |
−1.70 to 2.80 Mean =+ 0.34±0.92 |
0.64 |
| BMD femoral neck (g/cm2) | 0.780 to 1517 (§) Mean = 1080±0.172 |
0.732 to 1381 Mean = 1043±0.142 |
0.842 to 1443 Mean = 1112±0.123 |
0.20 |
| Body composition | ||||
| Median total fat (g) (IQR) | 20.225 (16.927 to 31.318) |
30.527 (23.343 to 34.182) |
24.095 (14.543 to 29.082) |
0.009(a) |
| Total lean mass (g)– mean ± SD | 50.597 ± 7.830 | 41.459 ± 4.414 | 55.758 ± 7.036 | <0.0001(a)(b) |
| Fat distribution FMI- mean ± SD | 8.31 ± 3.35 | 11.15 ± 3.17 | 7.78 ± 3.55 | 0.0003 (a) |
| Median visceral fat (g) (IQR) | 483.0 (142.0 to 781.0) |
465.0 (249.0 to 714.0) |
692.0 (269.3–1302) |
0.11 |
| Lean mass distribution RSMI (kg/m2)- mean ± SD | 7.84 ± 1.27 | 6.91 ± 0.69 | 8.47 ± 1.06 | <0.0001 (a)(b) |
| Lean mass distribution Index FNIH – mean ± SD | 0.89 ± 0.12 | 0.69 ± 0.11 | 0.97 ± 0.13 | <0.0001(c) |
(§), study in 25 individuals; BMD, bone mineral density; FMI, fat mass index; FNIH, Foundation for the National Institute of Health; IQR, interquartile range; RSMI, relative skeletal muscle mass index; SD, standard deviation; n, number.
(a)-Difference statistically significant between transgender and females;
(b)-Difference statistically significant between transgender and males;
(c)- Difference statistically significant does not include the sample of transgender.
Discussion
Our results have shown that our sample of transwomen had spine Z-score lower than females, and lower Z femur score than both controls. Most of body composition values (lean and fat mass) revealed intermediated values between female and male controls. Lean mass values correlated positively with femur BMD but neither the type of treatment received nor the time that they were used impacted bone mass.
Fighera et al17 also found that transwomen had BMD (g/cm2) of spine and femoral neck region lower than female and male controls and that total femoral BMD was lower when compared to males. The prevalence of low bone mass in this study was of 18%. Also, T’Sjoen et al,5 that studied a sample of 50 transwomen without control for comparison, found a prevalence of low bone mass Z-score ≤−2.0 of 26% at lumbar spine and 2% at the total hip. Our sample, with a mean age of 29 years, had 12.9% individuals with Z-score ≤−2.0 in at least one region. These results are unexpected as most of them received estrogens (83.8%) and the beneficial actions of estrogens in bone metabolism are well known as they inhibit the osteoclast function and thereby lower bone resorption.18 It is possible that the anti-androgen use could be blurring estrogens protective effect. Testosterone affects the bone homeostasis as it is aromatized to estrogens19 and it is well known that males on anti-androgens therapy for prostate cancer treatment are on risk for osteoporosis. According to Butoescu et al, these patients may loose from 2 to 10% of their bone mineral density at their hip and radius after 12 months of anti-androgen therapy, starting very early in the course of treatment.19 Likewise, anti-androgens may affect body composition decreasing lean body mass and thus affecting bone mass.20 Low lean body mass increases fracture risk in elderly patients.21 In our study, lean body mass of the transwomen group correlated with femoral bone density; no correlations were found with fat mass presently.
In some aspects, our results differ from previous studies. Mueller et al4 studying 84 male-to-female transsexuals found an increase in spine BMD without changes in femoral bone density after use of hormonal treatment and concluded that it appears there is no risk of osteoporosis in this group. In their sample, a uniform dose of estrogens and gonadotrophin-releasing hormone agonist was administered. This was not so in our study; the highest dose of estrogen used in this sample was of 4 mg/day. Also, a metanalysis and systematic review including 19 other studies and 812 transwomen concluded that hormone therapy had a neutral result on BMD at all sites evaluated, except the lumbar spine where a small increase in bone mass was detected.22
A study on serum hormonal levels of transwomen on hormonal treatment has shown that they had lower estrogen levels than females and lower testosterone levels than males17 and such disbalance may put them at disadvantage regarding bone mass. Different degrees of this imbalance, resulting from different doses of administered hormones, may explain the contradictory results found in literature. Removing the testosterone effect on the bones without replacing it for adequate doses of estrogens may be the problem.
Another given explanation for low bone mass in this context is that the transwomen group have lower levels of physical activity.2 This did not apply to the group in this study as they had levels of activity better than the controls evaluated by IPAQ questionnaire.23
This study has several limitations due to its cross-sectional design as well as the limited number of the sample and the heterogeneity of hormonal treatment. However, it does reflect the real life scenario in our region and highlights the risk of low bone mass in this group. Cross-sex hormonal therapy may be important for individuals that feel the discrepancy between their birth sex and the sense of being male or female, as there is some evidence that such treatment improves their well-being and quality of life,24 but it is important to be aware of their side-effects. Therefore, clinicians caring for transgender individuals should include bone mass evaluation in their daily practice to prevent and treat those affected.
Conclusions
This study showed that transwomen individuals are at risk of low bone mass that is increased in relation to female and male controls. In addition, low bone mass is found frequently in transwomen and it is correlated with lean body mass.
Contributor Information
Kadija Rahal Chrisostomo, Email: kadijarahalc@gmail.com.
Thelma L. Skare, Email: tskare@onda.com.br.
Henrique Rahal Chrisostomo, Email: riquerahalch@gmail.com.
Edna J. Litenski Barbosa, Email: ednajlbarbosa@gmail.com.
Renato Nisihara, Email: renatonisihara@gmail.com.
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