Table 1.
Demographics, time receiving treatment, and medication received. Bone mineral density (BMD) and method of evaluation and study conclusions related to bone structure, bone metabolism, and bone mineral density. Variability was observed in drug dosages and regions for BMD. M, male; F, female.
| Author, Year of Publication, Location |
Sample | Time Receiving the Treatment | Hormone and Dosage | Method of Evaluation for the Bone Mineral Density (BMD) and Area of Evaluation | Bone Mineral Density (Adjusted) | Study Conclusions Related to Bone Structure, Bone Metabolism and BMD | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| M to F Transwomen | F to M Transmen | M to F | F to M | Before OR Controls | After OR Test | |||||
| Schlatterer K et al. 1998 [37] Berlin, Germany | 10 | 10 | 11.5 years | Parenteral high doses of estrogens + Cyproterone Acetate or Estrogens alone (2–8 mg/day) | Parenteral testosterone esters (250 mg every 2–4 weeks) | Conventional whole-body CT scanner | M to F | 195 ± 20 mgr/ccm | 174 ± 3 mgr/ccm | Slight reduction in the BMD of M to F M to F and F to M transsexuals treated with the proposed cross-gender hormone concept possess low risk of osteoporotic change |
| F to M | 174 ± 3 mgr/ccm | 172 ± 2 mgr/ccm | ||||||||
| Sosa M et al. 2003 [38] Canary Islands, Spain | 53 | - | 201 ± 108 months or (16.75 ± 9) years | Ethinyl oestradiol + ciproterone acetate, -Oral estrogens and oestradiol valerate Specific dosages were not provided | - | Densitometer BMD of the lumbar spine and femoral neck | M to F | Lumbar Spine 1.002 ± 0.155 (gr/cm2) | Lumbar Spine 1.091 ± 0.150 (gr/cm2) | The chronic administration of estrogens in men may produce an increase in serum estradiol, a decrease in free testosterone levels, and an increase in BMD—Both in lumbar spine and in femoral neck. This study suggests that the bone of adult men is sensitive to estrogens. |
| Femoral Neck 0.808 ± 0.135 (gr/cm2) | Femoral Neck 0.904 ± 0.135 (gr/cm2) | |||||||||
| Ruetsche AG et al. 2005 [39] Berne, Switzerland | 24 | 15 | 12.5 years M-F 2.1 years before surgery and 9.7 years after surgery F-M 1.3 Years before surgery and 6.1 years after surgery | Cyproterone acetate 2 mg/day + Ethinyl estradiol 35 µg/day or a free combination of Cyproterone acetate 2 mg/day + Ethinyl estradiol 35–100 µg/day After surgery, Estradiol valerate or Micronized 17-beta estradiol 2–4 mg/day. |
Parenteral testosterone esters 250 mg/IM every 3 weeks Continued after surgery | Dual-energy X-ray absorptiometry (DXA) BMD of the lumbar spine, femoral neck, whole body, distal epiphysis, and other 5 areas | M to F | Lumbar spine 1.078 ± 0.131 (gr/cm2) | Lumbar spine 1.056 ± 0.137 (gr/cm2) | Biochemical values of calcium phosphate metabolism parameters were within normal ranges and comparable across groups. In transsexual genetic males and females under long term cross-sex hormone treatment, BMD values are generally preserved or increased. Non-compliance with cross-sex hormone treatment may lead to low BMD, only in genetic males. IGF-1 (Insulin like growth factor) could play a role in the mediation of the effect of androgens on bone in F-M transsexuals. |
| Femoral neck 0.835 ± 0.100 (gr/cm2) | Femoral Neck 0.774 ± 0.095 (gr/cm2) | |||||||||
| - | Whole body 1.216 ± 0.098 (gr/cm2) | |||||||||
| F to M | Lumbar spine 1.100 ± 0.139 (gr/cm2) | Lumbar spine 1.075 ± 0.088 (gr/cm2) | ||||||||
| Femoral neck 0.937 ± 0.121 (gr/cm2) | Femoral Neck 0.842 ± 0.058 (gr/cm2) | |||||||||
| - | Whole body 1.179 ± 0.035 (gr/cm2) | |||||||||
| Lapauw B et al. 2008 [40] Ghent, Belgium | 23 | - | >3 years At least 3 years under hormone treatment. Al the patients had sex reassignment surgery | Before surgery Cyproterone acetate 50–100 mg/day + ethinyl estradiol 25–50 μg/day After surgery either: -Ethinyl estradiol 25–50 μg/day (8 participants) -Estradiol valerate 2 mg/day (10 participants) -Conjugated equine estrogens1.25 mg/day (2 participants) -Transdermal estradiol gels (3 persons) | - | Dual-energy X-ray absorptiometry (DXA) BMD at the lumbar spine, distal forearm and Peripheral quantitative computed tomography (pQCT), at the same areas for analysis of the bone architecture | M to F | Lumbar spine 1.05 ± 0.11 (gr/cm2) | Lumbar spine 0.92 ± 0.14 (gr/cm2) | M to F transsexual persons presents: Lower muscle mass and strength and higher fat mass Lower trabecular bone density and BMD at various sites and smaller cortical bone size as compared to healthy age- and height-matched controls. The lower level of sports-related physical activity as well as the pharmacological and surgical withdrawal from endogenous T production could contribute to these findings. Male-to-female transsexuals may be at increased risk for developing osteoporosis and related fractures. Bone health should be a parameter of interest in the long-term follow-up care for male-to-female transsexual persons. |
| Distal forearm 0.49 ± 0.05 (gr/cm2) | Distal forearm 0.42 ± 0.07 (gr/cm2) | |||||||||
| T’Sjoen G et al. 2009 [41] Ghent, Belgium | 50 | - | >3 years and at least 1 year after sex reassignment | Cyproterone acetate 50–100 mg/day (1 year) + exogenous estrogen administration | - | Dual-energy X-ray absorptiometry (DXA) BMD at the lumbar spine, proximal femur and the distal radius of the nondominant site AND pQCT for the analysis of bone architecture | M to F | - | Lumbar spine 0.959 ± 0.159 | Low bone mass, smaller bone size, and reduced muscle mass. Are highly prevalent in the described group of M-F transsexual persons Androgen deficiency or an inadequate estrogen dosage could be the cause Hormonal protocols differ between different centers and individual changes in BMD are highly variable There is a need for longitudinal single- and multi-center data on low bone mass risk in the M/F transsexual group. |
| Total hip 0.940 ± 0.150 | ||||||||||
| Radius and 0.432 ± 0.077 | ||||||||||
| Van Caenegem, et al. 2012 [42] Ghent, Belgium | - | 66 50 undergone surgery and received hormone therapy 16 Just hormone therapy |
8.7 years after sex reassignment surgery (SRS) with a minimum of 9 months and a maximum of 22 years. | - | Testosterone decanoate 100 mg, Testosterone isocaproate OR fenylpropionate 60 mg, Testosterone propionate 30 mg/mL; 2–3 weeks (35 patients); Testosterone undecanoate 1000 mg; 12 weeks (7 patients); Transdermal testosterone 50 mg daily (8 patients) Testosterone undecanoate 40 mg/day + testosterone gel 50 mg per 5 g, 50 mg daily (1 Patient) | Dual-energy X-ray absorptiometry (DXA); BMD at the lumbar spine, and left proximal femur (total hip and femoral neck region) | F to M | Lumbar spine 1.06 ± 0.11 (gr/cm2) | Lumbar spine 1.03 ± 0.10 (gr/cm2) | Transmen (F-M) with hormone treatment and after SRS possess a bone and body composition comparable to men, compared with age-matched female controls. This is less fat mass, more central pattern of adiposity, more muscle mass, strength, and larger cortical bone size. The differences may result from the effects of long-term testosterone administration and of diminished estrogen exposure and/or from indirect effects through muscle mass and strength. Transsexual men (F to M) on long-term hormonal therapy do not have an increased risk of low bone mass but associated cardiovascular risk factors are important to address. |
| Femoral neck 0.84 ± 0.10 (gr/cm2) | Femoral neck 0.82 ± 0.11 (gr/cm2) | |||||||||
| Total hip 0.95 ± 0.10 (gr/cm2) | Total hip 0.96 ± 0.12 (gr/cm2) | |||||||||
| Wierckx K et al. 2012 [43] Ghent, Belgium | 50 | 50 | ±10 years | Before surgery Cyproterone acetate 50–100 mg/day/1 year different +exogenous estrogen After surgery all received estrogens (3 patients did not followed the estrogen protocol) | Testosterone | Dual-energy X-ray absorptiometry (DXA); BMD at the lumbar spine, at the proximal femur (total hip region), and a both distal forearms | M to F | Data not shown | Data not shown | After an average of 10 years of hormone treatment no important side effects were reported and osteoporosis was not observed in transsexual men (F to M). Transsexual women (M to F) suffered from osteoporosis at the lumbar spine and distal arm. Twelve percent of transsexual women (M to F) experienced thromboembolic and/or other cardiovascular events during hormone treatment, possibly related to older age, estrogen treatment, and lifestyle factors. In order to decrease cardiovascular morbidity, more attention should be paid to decrease cardiovascular risk factors during hormone therapy management. |
| F to M | Data not shown | Data not shown | ||||||||
| Wiepjes C et al. 2018 [44] Amsterdam, Netherland | 711 | 543 | 10 years | Oral or transdermal estrogens and anti-androgens until gonadectomy | Oral, transdermal, or intramuscular testosterone. | Dual-energy X-ray absorptiometry (DEXA) at 2, 5, and 10 years Absolute BMD | M to F | Male and Female adult reference population | 0.956 (+0.006) (gr/cm2) | This study showed that hormone therapy does not negatively affect the BMD Regularly assessing BMD should be completed just when osteoporotic risk is present (>60 years age) High percentage of low BMD was found prior to hormone therapy in transwomen. Therefore, evaluation of BMD before start of hormone therapy may be considered. |
| F to M | Male and Female adult reference population | 1.45 (+0.008) (gr/cm2) | ||||||||
| Broulik PD et al. 2018 [45] Prague, Czech Republic | - | 35 | 18 years | - | Before surgery Testosterone isobutyrate Sex reassignment surgery (hysterectomy, ovariectomy, and bilateral mastectomy) After surgery Testosterone isobutyrate 25 mg intramuscular every week, OR Testosterone propionate 250 mg every third week intramuscular OR Testosterone undecanoate 40 mg 4 times day. | Dual-energy X-ray absorptiometry (DXA); BMD at the lumbar spine and femoral neck | F to M | Male controls | Lumbar spine 1.213 ± 0.15 | BMD after adequate dose of testosterone therapy is higher after 18 years of testosterone administration BMD at the spine its similar to baseline after 18 years of testosterone administration. Androgens compensate for the low estrogen level in the bone metabolism |
| Lumbar spine 1.203 ± 0.065 | ||||||||||
| Femoral neck 1.192 ± 0.19 | ||||||||||
| Female controls | Femoral neck 0.950 ± 0.11 | |||||||||
| Lumbar spine 1.192 ± 0.19 | ||||||||||
| Femoral neck 0.822 ± 0.09 | ||||||||||
| Summary of Findings | M to F 921 | F to M 719 | Time Receiving the Treatment (Range) >3 years to 18 years | M to F Hormone Therapy Cyproterone Acetate (Antiandrogen) Estrogens | F to M Hormone Therapy Testosterone | BMD Method of Evaluation Conventional whole-body scanner; Dual-energy X-ray absorptiometry (DXA) | - | - | BMD Contradictory results, the BMD was preserved or increased in 788 M to F patients (82.66%); BMD decreased in 73 M to F patients (8.47%); BMD Increased in 35 F to M patients (4.93%); BMD preserved in 674 F to M patients (95.06%) | |