Bone Health · Bone Mineral Density
Abstract
Purpose
Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity).
Methods
Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ).
Results
14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people.
Conclusions
Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.
Topics
By this author
Semen Analysis · Sperm Function Testing
Preimplantation genetic testing for male factor infertility: lights and shadows
Mazzilli R et al., 2026 · Journal of endocrinological investigation
Male factor could contribute, alone or in combination with female factor, to the inability to conceive in a couple in more than half of cases. The effect of male factor infertility (MFI) on embryological assisted reproductive technology (ART) outcomes remains an ongoing discussion. to evaluate the impact of MFI on embryo aneuploidy rates, to better understand the role and possible indication for Preimplantation genetic testing for aneuploidies (PGT-A), considering the role of sperm characteristics, paternal age, sperm DNA fragmentation and sperm aneuploidies. this narrative review included all available articles, published up to January 2026. Available evidence, often based on heterogeneous and old-fashioned methodologies, suggests that MFI may impair embryonic development, particularly in terms of fertilization rate and blastulation rate, more than embryo euploidy; however, a comprehensive evaluation of MFI should be integrated into clinical practice in the context of couple infertility, to also optimize the efficiency and outcomes of ART. Promising results emerged from sperm DNA fragmentation as a tool to predict embryo euploidy, but further investigations involving larger sample sizes and improved standardization are required.
Male Factor Causes · Hormonal Causes
Pathophysiology-Based Classification of Male Infertility: Evidence from an 800-patient Prospective Cohort
Grande G et al., 2026 · The Journal of clinical endocrinology and metabolism · Free to read
Male factor infertility (MFI) is frequently labelled idiopathic when evaluation relies primarily on semen analysis, potentially overlooking endocrine and pathophysiological mechanisms relevant for targeted management. To phenotypically define MFI and develop a pathophysiology-based classification aimed at reducing idiopathic infertility following comprehensive evaluation. Prospective monocentric cohort study conducted at a tertiary referral academic centre. Eight hundred male partners of infertile couples evaluated between October 2024 and January 2026 after exclusion of isolated female factor infertility. Prevalence of MFI categories, hormonal patterns across phenotypes, and proportion of idiopathic infertility after comprehensive work-up. All patients underwent standardized clinical evaluation, hormonal assessment (total testosterone, FSH, LH), testicular ultrasound, and complete semen analysis. Microbiological testing, transrectal ultrasound, and genetic analyses were performed according to guidelines. Primary spermatogenic failure was the most prevalent category (56.0%), followed by infection/inflammation (22.4%) and hypogonadotropic hypogonadism (8.5%). Idiopathic infertility was identified in only 5.3% of cases. Distinct endocrine profiles were observed, with high-FSH spermatogenic failure representing the dominant phenotype. Comprehensive phenotyping markedly reduces the proportion of patients classified as having idiopathic infertility and identifies clinically relevant subgroups. This prospective study provides validation of a pathophysiology-based classification and supports a shift toward endocrine-integrated diagnostic strategies in male infertility, with potential implications for targeted management.
Semen Analysis · Reference Standards
Semen Quality in Transgender Individuals Seeking Fertility Preservation
Ponce MR et al., 2026 · Andrology · Free full text on PubMed Central
Transgender individuals assigned male at birth (AMAB) may choose to preserve their fertility prior to starting gender-affirming hormone therapy (GAHT). However, limited data exist regarding the baseline reproductive and hormonal characteristics of this population before and after GAHT. To characterize semen quality and hormonal profiles in transgender AMAB individuals prior to GAHT and compare findings with cisgender men and with transgender individuals who discontinued GAHT for at least 3 months. This retrospective study included transgender AMAB individuals from two tertiary andrology centers who underwent sperm cryopreservation before GAHT initiation (treatment-naïve group). Clinical evaluation included anthropometric measures, testicular volume assessment, varicocele detection, and sex hormone measures. Semen parameters were analyzed according to WHO criteria and compared with those of cisgender men and previously treated transgender individuals. Thirty-two treatment-naïve transgender AMAB individuals were included. Hormonal parameters were generally within reference ranges. Only 46.9% of treatment-naïve individuals met WHO criteria for normozoospermia, compared with 75.5% of cisgender controls. Compared with nine previously treated individuals, estradiol levels were higher and seminal volume lower. A higher frequency of seminal abnormalities was observed, although not statistically significant. A substantial proportion of treatment-naïve transgender AMAB individuals exhibited impaired semen parameters prior to GAHT initiation. Prior GAHT exposure showed a trend toward poorer semen quality. These findings support early fertility counseling and preservation in transgender individuals prior to GAHT initiation.
Neoplastic Risk in Patients With Klinefelter Syndrome
Graziani A et al., 2026 · Andrology · Free to read
Besides gonadal involvement (hypogonadism, male factor infertility, and testicular hypotrophy), patients with Klinefelter syndrome (KS) may suffer from several extra-gonadic complications, including neoplastic events. The aim of this review is to summarize all major clinical evidence dealing with the association between KS and neoplastic diseases and provide practical suggestions for the management of patients with KS regarding neoplastic risk. This narrative review was conducted through a comprehensive search of the PubMed database, using combinations of the following keywords: "Klinefelter syndrome," "cancer," "neoplasm," "breast cancer," "germ cell tumor," "lymphoma," and "testosterone replacement therapy". KS is associated with a higher risk of breast cancer and mediastinal germ cell tumors and an apparent higher risk of hematological malignancies, in particular non-Hodgkin lymphoma and leukemia. Evidence on testicular cancer is limited, with no clear increase in risk attributable to KS, while prostate cancer has a lower risk and lower mortality rate. Given the complexity of the syndrome and the limited available evidence, regular clinical follow-up with targeted investigations when clinically indicated may facilitate early diagnosis and management of associated comorbidities.
Related research
Bone Mineral Density · Peak Bone Mass
Age-dependent bone mineral density responses to gender-affirming hormone therapy in transgender individuals: a one-year prospective study
Ceolin C et al., 2025 · Journal of endocrinological investigation · Free full text on PubMed Central
Evidence on the skeletal effects of gender-affirming hormone therapy (GAHT) in transgender individuals remains limited, especially across age groups. Individuals assigned male at birth (AMAB) often show reduced bone mineral density (BMD) even before GAHT, whereas findings in those assigned female at birth (AFAB) are more variable. Given the key role of adolescence and early adulthood in peak bone mass, timely skeletal assessment is essential. This study compared BMD before and after one year (1-y) of GAHT to age-matched cisgender controls. Prospective observational study involving 269 adults (162 transgender and 107 cisgender controls) conducted at the University Hospital of Padua (January 2020-November 2024). Dual-energy X-ray absorptiometry (DXA) was performed at baseline and after 1-y of GAHT. After 1-y of GAHT, in AMAB individuals, lumbar spine BMD significantly increased (from 0.97 ± 0.16 to 1.02 ± 0.14 g/cm², p < 0.001), particularly in those under 20 years. AFAB individuals experienced a modest but significant reduction in femoral neck BMD (from 0.81 ± 0.12 to 0.79 ± 0.13, p < 0.05), especially in the 20–30-year age group. Age-stratified analyses revealed that younger participants showed greater BMD improvements, while those over 20 exhibited stable or declining values. Linear regression confirmed age as an independent predictor of BMD change, with older age associated with reduced skeletal responsiveness to GAHT at key femoral sites. GAHT has variable effects on bone health, influenced by age and sex assigned at birth. Early initiation may favor bone accrual, especially in AMAB individuals, while AFAB individuals may require closer monitoring for site-specific bone loss during testosterone therapy.
Bone Mineral Density · Measurement
Impact of reference gender on bone mineral density and fracture risk assessment in transgender adults
Scala A et al., 2026 · Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · Free full text on PubMed Central
In transgender adults, reference-gender choice alters Z-scores and fracture-risk estimates. Z-scores differ by 0.4-0.6 SD, with male references identifying more individuals with low BMD for age, especially in those assigned male at birth. Dual-reference reporting is advisable until further evidence becomes available. Transgender individuals, especially those assigned male at birth (AMAB), exhibit lower bone mineral density (BMD) compared with the cisgender population. Interpretation of densitometric data is challenging, as the choice of reference gender can significantly influence Z-scores and fracture risk scores. This study aims to evaluate the impact of the gender reference database (male or female) on the assessment of BMD and fracture risk in transgender adults prior to gender-affirming hormone therapy (GAHT). We conducted a cross-sectional analysis of 249 transgender individuals (153 assigned female at birth - AFAB and 96 AMAB) aged 18-43 years, recruited in the Hospitals of Padua and Brescia (Italy). Z-scores were calculated using both male and female reference databases and FRAX scores were computed using both gender inputs. Associations with anthropometric, biochemical, and hormonal parameters were explored. Z-scores differed systematically depending on the reference gender, with mean ΔZ ranging 0.4-0.6 SD across skeletal sites. Switching reference databases frequently led to reclassification of BMD status. AMAB individuals showed a higher prevalence of low BMD for age, particularly when assessed against male references (27.1%), whereas AFAB participants generally maintained normal BMD. However, FRAX scores remained low. BMI and 25-OH vitamin D levels were independent predictors of BMD and Z-scores in AMAB individuals. The choice of reference gender significantly influences densitometric interpretation in young transgender adults. Until further evidence becomes available, calculating Z-scores using both male and female reference databases is advisable. Early preventive interventions remain essential to preserve bone health.
Bone Mineral Density · Peak Bone Mass
Impact of gender-affirming treatment on bone health in transgender and gender diverse youth
Ciancia S et al., 2022 · Endocrine connections · Free full text on PubMed Central
Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to start using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantly deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in particular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.
Bone Mineral Density · Peak Bone Mass
Spinal bone mineral density in premenopausal vegetarian and nonvegetarian women: cross-sectional and prospective comparisons
Barr SI et al., 1998 · J Am Diet Assoc
To compare spinal bone mineral density (BMD) and 1-year BMD change between premenopausal vegetarian and nonvegetarian women. Cross-sectional comparison of spinal BMD at baseline and prospective comparison of a subsample. A western Canadian metropolitan area. Subjects/samples: Healthy vegetarian (n = 15 lacto-ovo-vegetarian, n = 8 vegan) and nonvegetarian (n = 22) women aged 20 to 40 years, with regular menstrual cycles and stable body weight completed baseline measurements. Twenty of these women (6 lacto-ovo-vegetarian, 5 vegan, 9 nonvegetarian) participated in repeat measurements at approximately 13 months. Statistical Analyses Performed: Descriptive statistics, independent sample and paired t tests, 1-way analysis of variance, correlation analysis, and stepwise multiple regression were used to compare groups and to assess associations with BMD. At baseline, subjects were 27.2 +/- 5.1 years old. Vegetarians had lower body mass index (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < .05) and percent body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < .05); they also tended to have lower BMD (1.148 +/- 0.111 g/cm2 vs 1.216 +/- 0.132 g/cm2, P = .06), although this was not apparent with weight as a covariate (P = .14). Baseline BMD was predicted by vitamin B-12 intake and total body fat (R2 = .24, P = .001). Participants in the follow-up differed only in their being older than nonparticipants. Over 1 year, mean BMD increased significantly (1.1%): by diet group, nonvegetarians' BMD increased but vegetarians' BMD was unchanged. No other monitored variables were associated with BMD change. Applications/ Vegetarian women should be aware of links between low BMD and low body weight/body fat, and should maintain adequate intakes of nutrients believed to affect BMD.
Bone Health › Bone Mineral Density › Measurement · Lifestyle and Environment › Nutrition and Metabolic Health › Body Weight and Composition
M De Rui
PMID 37450195 37450195 DOI 10.1007/s40618-023-02156-7 10.1007/s40618-023-02156-7 Ceolin et al. 2024, Ceolin 2024