Effect of Sex Steroids on the Bone Health of Transgender Individuals: A Systematic Review and Meta‐Analysis

Background: The impact of sex steroids on bone health in transgender individuals is unclear. Methods: A comprehensive search of several databases to 7 April 2015 was conducted for studies evaluating bone health in transgender individuals receiving sex steroids. Pairs of reviewers selected and appraised studies. A random effects model was used to pool weighted mean differences and 95% confidence intervals (CIs). Results: Thirteen studies evaluating 639 transgender individuals were identified [392 male‐to‐female (MTF), 247 female‐to‐male (FTM)]. In FTM individuals and compared with baseline values before initiation of masculinizing hormone therapy, there was no statistically significant difference in the lumbar spine, femoral neck, or total hip bone mineral density (BMD) when assessed at 12 and 24 months. In MTF individuals and compared with baseline values before initiation of feminizing hormone therapy, there was a statistically significant increase in lumbar spine BMD at 12 months (0.04 g/cm2; 95% CI, 0.03 to 0.06 g/cm2) and 24 months (0.06 g/cm2; 95% CI, 0.04 to 0.08 g/cm2). Fracture rates were evaluated in a single cohort of 53 MTF and 53 FTM individuals, with no events at 12 months. The body of evidence is derived mostly from observational studies at moderate risk of bias. Conclusion: In FTM individuals, masculinizing hormone therapy was not associated with significant changes in BMD, whereas in MTF individuals feminizing hormone therapy was associated with an increase in BMD at the lumbar spine. The impact of these BMD changes on patient‐important outcomes such as fracture risk is uncertain.

[1]  M.,et al.  Changes [I] , 2018, The Complete Poems of William Barnes, Vol. 2: Poems in the Modified Form of the Dorset Dialect.

[2]  W. Van den Noortgate,et al.  Systematic Review and Meta-Analysis of Prevalence Studies in Transsexualism , 2015, European Psychiatry.

[3]  H. Daniel,et al.  Lesbian, Gay, Bisexual, and Transgender Health Disparities: Executive Summary of a Policy Position Paper From the American College of Physicians. , 2015, Annals of internal medicine.

[4]  J. Cauley Estrogen and bone health in men and women , 2015, Steroids.

[5]  Melissa L Rethlefsen,et al.  Librarian co-authors correlated with higher quality reported search strategies in general internal medicine systematic reviews. , 2015, Journal of clinical epidemiology.

[6]  J. Safer,et al.  Hormone therapy in transgender adults is safe with provider supervision; A review of hormone therapy sequelae for transgender individuals , 2015, Journal of clinical & translational endocrinology.

[7]  A. Heijboer,et al.  Bone mass in young adulthood following gonadotropin-releasing hormone analog treatment and cross-sex hormone treatment in adolescents with gender dysphoria. , 2015, The Journal of clinical endocrinology and metabolism.

[8]  J. Kaufman,et al.  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). , 2014, European journal of endocrinology.

[9]  A. Bazzocchi,et al.  Effects of three different testosterone formulations in female-to-male transsexual persons. , 2014, The journal of sexual medicine.

[10]  J. Lindsay,et al.  Access to care for transgender veterans in the Veterans Health Administration: 2006-2013. , 2014, American journal of public health.

[11]  J. Kaufman,et al.  Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European network for the investigation of gender incongruence. , 2014, The journal of sexual medicine.

[12]  Simon G A Brown Treatment failure in osteoporosis. , 2012, Menopause international.

[13]  W. J. Meyer,et al.  Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7 , 2012 .

[14]  S. Cummings,et al.  Treatment failure in osteoporosis , 2012, Osteoporosis International.

[15]  J. Kaufman,et al.  Bone mass, bone geometry, and body composition in female-to-male transsexual persons after long-term cross-sex hormonal therapy. , 2012, The Journal of clinical endocrinology and metabolism.

[16]  M. Beckmann,et al.  Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals. , 2010, The journal of sexual medicine.

[17]  M. Beckmann,et al.  Body composition and bone mineral density in male-to-female transsexuals during cross-sex hormone therapy using gonadotrophin-releasing hormone agonist. , 2010, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[18]  V. Montori,et al.  Hormonal therapy and sex reassignment: a systematic review and meta‐analysis of quality of life and psychosocial outcomes , 2010, Clinical endocrinology.

[19]  V. Montori,et al.  Effect of sex steroid use on cardiovascular risk in transsexual individuals: a systematic review and meta‐analyses , 2010, Clinical endocrinology.

[20]  J. Ioannidis,et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. , 2009, Journal of clinical epidemiology.

[21]  C. Ohlsson,et al.  Estrogens as regulators of bone health in men , 2009, Nature Reviews Endocrinology.

[22]  S. Khosla,et al.  Androgens and bone , 2009, Steroids.

[23]  Gordon H Guyatt,et al.  Systematic reviewers commonly contact study authors but do so with limited rigor. , 2009, Journal of clinical epidemiology.

[24]  J. Kaufman,et al.  Body composition, volumetric and areal bone parameters in male-to-female transsexual persons. , 2008, Bone.

[25]  J. Cauley,et al.  Bone Mineral Density Changes during the Menopause Transition in a Multiethnic Cohort of Women , 2008 .

[26]  M. Beckmann,et al.  Long-term administration of testosterone undecanoate every 3 months for testosterone supplementation in female-to-male transsexuals. , 2007, The Journal of clinical endocrinology and metabolism.

[27]  P. Cohen-Kettenis,et al.  Clinical management of gender identity disorder in adolescents: a protocol on psychological and paediatric endocrinology aspects , 2006 .

[28]  I. Hoffmann,et al.  Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. , 2005, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[29]  M. Holick,et al.  Testosterone increases bone mineral density in female‐to‐male transsexuals: a case series of 15 subjects , 2004, Clinical endocrinology.

[30]  Ego Seeman,et al.  Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. , 2004, Bone.

[31]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[32]  E. Salido,et al.  Bone mass, bone turnover, vitamin D, and estrogen receptor gene polymorphisms in male to female transsexuals: effects of estrogenic treatment on bone metabolism of the male. , 2003, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[33]  S. Chanprasertyothin,et al.  The effects of oestrogen exposure on bone mass in male to female transsexuals , 1998, Clinical endocrinology.

[34]  P. V. van Kesteren,et al.  Long‐term follow‐up of bone mineral density and bone metabolism in transsexuals treated with cross‐sex hormones , 1998, Clinical endocrinology.

[35]  P. Lips,et al.  The effect of one-year cross-sex hormonal treatment on bone metabolism and serum insulin-like growth factor-1 in transsexuals. , 1996, The Journal of clinical endocrinology and metabolism.

[36]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[37]  P. Tugwell,et al.  The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses , 2014 .

[38]  J. Kaufman,et al.  Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study , 2014, Osteoporosis International.