A Comparative Analysis of Local and Systemic Immunological Biomarkers in Females With Breast Implants and Capsular Contracture.

Background: The etiology of capsular contracture (CC), the most common complication following breast augmentation, remains unclear. Chronic, fibrotic inflammation resulting in excessive fibrosis has been proposed as a potential mechanism. Objectives: In this study, we aimed to investigate the relation between biomarkers that are associated with inflammation and fibrosis and the severity of CC. Methods: Fifty healthy females were categorized into 3 groups: females with no-to-mild CC (Baker 1-2; n = 15), females with severe CC (Baker 3-4; n = 20), and a control group awaiting breast augmentation (n = 15). We assessed 5 biomarkers (galectin-1 [Gal-1], interferon-ß [INF-ß], interferon-γ [INF-γ], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) in breast implant capsules and serum samples. Results: No significant differences in intracapsular cytokine levels were observed between the Baker 1-2 and the Baker 3-4 groups, as the levels were generally low and, in some cases, almost undetectable. In the blood samples, no significant differences in Gal-1, INF-γ, IL-6, or TNF-α levels were found within the 3 groups. We identified significantly increased levels of INF-ß (P = .009) in the blood samples of females with severe CC, driven mainly by 3 extremely high values. Conclusions: The cytokines assessed in this study did not reflect the degree of CC among females with silicone breast implants. However, 3 females with severe CC, who all had prolonged silicone exposure, showed extremely elevated levels of INF-ß in their serum samples. This possible association between prolonged silicone exposure and systemic inflammation in some females should be further investigated.

Silicone Migration from Intact Saline Breast Implants.

Breast augmentation is a widely performed surgical procedure worldwide, predominantly using silicone gel-filled implants. Concerns have primarily revolved around ruptures and the potential health risks associated with leaked silicone from silicone gel-filled implants. Cases of silicone migration from the shell of saline breast implants remain scarce. This case report introduces a unique case of a 66-year-old patient with silicone migration from intact saline breast implants. The patient presented with a range of symptoms consistent with breast implant illness. Radiological findings suggested the presence of silicone in the axillary lymph nodes, despite the integrity of the implants, thereby confirming silicone migration. Histopathological evaluation revealed a foreign body reaction and the presence of silicone in the axillary lymph nodes. Given the saline filling, the source is likely the polydimethylsiloxane shell. The rarity of documented silicone migration from intact saline breast implants, especially in patients with breast implant illness, underscores the need for more research into the health implications of leaked silicone particles from breast implants.

Addition of progesterone to feminizing gender-affirming hormone therapy in transgender individuals for breast development: a randomized controlled trial.

BACKGROUND: Feminizing gender-affirming hormone therapy (GAHT) for transgender individuals traditionally includes estradiol and androgen deprivation. Research has demonstrated that breast size as a result of GAHT in transgender women is often limited. Therefore, transgender women often choose to undergo breast augmentation surgery. Progesterone is important for breast development in cisgender women during puberty. A potential role for progesterone in breast development in transgender women has not been investigated in a randomized controlled experimental set-up. The primary objective of this study is to explore the effects on breast volume of addition of oral progesterone to GAHT with estradiol in transgender women after vaginoplasty or orchiectomy. Secondary objectives include assessment of safety, satisfaction, mood, sleep and sexual pleasure. METHODS: This is a non-blinded, non-placebo, randomized controlled trial using a factorial design in adult transgender individuals assigned male sex at birth who have undergone GAHT for at least one year and underwent vaginoplasty or orchiectomy. The study design allows for rapid assessment of potential synergistic effects of various dose combinations of estradiol and progesterone on breast volume change: Ninety participants will be randomized into six groups of 15 subjects each, receiving either the baseline dose of estradiol, the baseline dose of estradiol and progesterone 200 mg daily, the baseline dose of estradiol and progesterone 400 mg daily, twice the baseline dose of estradiol, twice the baseline dose of estradiol and progesterone 200 mg daily or twice the baseline dose of estradiol and progesterone 400 mg daily, all for a duration of 12 months. The main study parameters include changes in breast volume as determined by 3D measurements. Participants will be followed-up with laboratory testing including serum progesterone concentrations as well as surveys for satisfaction, mood, sleep quality and sexual pleasure. DISCUSSION: This study will indicate whether progesterone is safe and of additional value with regard to breast volume change in transgender individuals receiving feminizing GAHT. The results of this study will be useful for innovation of feminizing GAHT. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform: EUCTR2020-001952-16-NL; date of registration: 12 December 2020 https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2020-001952-16-NL .

Skin cancer incidence in transgender individuals receiving gender-affirming hormone treatment: a nationwide cohort study in the Netherlands.

BACKGROUND: Development of skin cancer, in particular melanoma, has been linked to sex hormones. We aimed to determine the incidence of skin cancer in transgender individuals receiving gender-affirming hormone treatment (GAHT). METHODS: In this nationwide retrospective cohort study, clinical information of participants who visited our clinic between (the years) 1972 and 2018 and received GAHT was integrated with national pathology and cancer statistics data in order to assess skin cancer incidence. Standardized incidence ratios (SIRs) were calculated. RESULTS: The cohort consisted of 2,436 trans women and 1,444 trans men. The median age at the start of GAHT was 31 years (IQR 24-42) in trans women and 24 years (IQR 20-32) in trans men. The median follow-up time for trans women was 8 years (IQR 3-18) with a total follow-up time of 29,152 years and 4 years (IQR 2-12) with a total follow-up time of 12,469 years for trans men. Eight trans women were diagnosed with melanoma (SIR 1.80 [95% CI 0.83-3.41] vs. all men; SIR 1.40 [0.65-2.65] vs. all women), and seven developed squamous cell carcinoma (SIR 0.78 [0.34-1.55] vs. all men; SIR 1.15 [0.50-2.27] vs. all women). Two trans men developed melanoma (SIR 1.05 [0.18-3.47] vs. all men; SIR 0.77 [0.14-2.70] vs. all women). CONCLUSIONS: GAHT did not appear to affect skin cancer incidence in this large cohort of transgender individuals. As skin cancer incidence increases with age and the proportion of elderly subjects is currently limited in this cohort, it will be worthwhile to repeat this analysis in the future.

Patient-reported systemic symptoms in women with silicone breast implants: a descriptive cohort study.

OBJECTIVE: An unknown portion of women with silicone breast implants (SBI) report development of systemic symptoms, recently named as 'breast implant illness (BII)'. We aim to describe the symptoms and characteristics of women with SBI reporting these systemic symptoms and compare the clinical course of women who chose to keep their implants, to women who had their implants removed. DESIGN: Observational cohort study. SETTING: Specialised BII out-patient clinic at Amsterdam UMC, the Netherlands, from 2011 to 2020. PARTICIPANTS: All women presenting to the BII clinic with SBI and systemic symptoms. RESULTS: 467 women were included for baseline analyses and 398 women for follow-up. Most frequently reported systemic symptoms at baseline included fatigue (88%), arthralgia (71%), morning stiffness (59%), myalgia (48%), cognitive impairment (33%), peripheral neurological symptoms (30%) and lymphadenopathy (22%). Furthermore, 56% reported pre-existing allergies at baseline and positive antinuclear antibodies were observed in 23%. At follow-up with a median of 3.3 years (IQR 2-4), 152 women had their implants removed on clinical grounds. Symptoms improved significantly in 65 women (43%), improved moderately in 37 women (24%), did not change in 37 women (24%) and deteriorated in 13 women (9%). Women who underwent explantation showed more improvement of their systemic symptoms compared with women who did not (OR 2.9, 95% CI 1.3 to 6.2). Additionally, women who underwent explantation within 10 years after implantation improved significantly better than women who got the implants removed after 10 years (p=0.007). Lastly, local symptoms decreased from 75% to 34% after implant removal (p<0.0001). CONCLUSION: Most women with SBI who developed systemic symptoms experienced improvement after explantation, especially when removed within 10 years after implantation. Early recognition of the pattern of systemic symptoms in women with SBI is important and implant removal should be considered.

Change in Visceral Fat and Total Body Fat and the Effect on Cardiometabolic Risk Factors During Transgender Hormone Therapy.

INTRODUCTION: Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease and is influenced by sex hormones. Our aim was to investigate changes in visceral fat and the ratio of visceral fat to total body fat (VAT/TBF) and their associations with changes in lipids and insulin resistance after 1 year of hormone therapy in trans persons. METHODS: In 179 trans women and 162 trans men, changes in total body and visceral fat estimated with dual-energy X-ray absorptiometry before and after 1 year of hormone therapy were related to lipids and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] with linear regression analysis. RESULTS: In trans women, total body fat increased by 4.0 kg (95% CI 3.4, 4.7), while the amount of visceral fat did not change (-2 grams; 95% CI -15, 11), albeit with a large range from -318 to 281, resulting in a decrease in the VAT/TBF ratio of 17% (95% CI 15, 19). In trans men, total body fat decreased with 2.8 kg (95% CI 2.2, 3.5), while the amount of visceral fat did not change (3 g; 95% CI -10, 16; range -372, 311), increasing the VAT/TBF ratio by 14% (95% CI 10, 17). In both groups, VAT/TBF was not associated with changes in blood lipids or HOMA-IR. CONCLUSIONS: Hormone therapy in trans women and trans men resulted in changes in VAT/TBF, mainly due to changes in total body fat and were unrelated to changes in cardiometabolic risk factors, which suggests that any unfavorable cardiometabolic effects of hormone therapy are not mediated by changes in visceral fat or VAT/TBF.

Incidence of testicular cancer in trans women using gender-affirming hormonal treatment: a nationwide cohort study.

OBJECTIVE: To assess the incidence of testicular cancer in trans women (male sex assigned at birth, female gender identity) using gender-affirming hormonal treatment. PATIENTS AND METHODS: Data of trans women starting hormonal treatment at our gender identity clinic between 1972 and 2017 were linked to the national pathology database to obtain testicular cancer diagnoses. The standardised incidence ratio (SIR) was calculated using the number of observed testicular cancer cases in our cohort and the number of expected cases based on age-specific Dutch incidence rates. Subgroup analyses were performed in testicular tissues sent for histopathological analysis at the time of bilateral orchidectomy, and when follow-up exceeded 5 years. RESULTS: The cohort consisted of 3026 trans women with a median follow-up time of 2.3 interquartile range (IQR) (1.6-3.7) years. Two testicular cancer cases were identified whilst 2.4 cases were expected (SIR 0.8, 95% confidence interval 0.1-2.8). In addition, one testicular cancer case was encountered in an orchidectomy specimen (0.1%). In the 523 trans women with a follow-up time of >5 years (median [IQR] 8.9 [6.4-13.9] years), no testicular cancer was observed. CONCLUSION: Testicular cancer risk in trans women is similar to the risk in cis men. The testicular cancer cases occurred within the first 5 years after commencing hormonal treatment, and the percentage of cases encountered at the time of bilateral orchidectomy was low. As no testicular cancer was observed in trans women with a long follow-up period, long-term hormonal treatment does not seem to increase testicular cancer risk.

Mortality trends over five decades in adult transgender people receiving hormone treatment: a report from the Amsterdam cohort of gender dysphoria.

BACKGROUND: Increased mortality in transgender people has been described in earlier studies. Whether this increased mortality is still present over the past decades is unknown. Therefore, we aimed to investigate trends in mortality over five decades in a large cohort of adult transgender people in addition to cause-specific mortality. METHODS: We did a retrospective cohort study of adult transgender people who visited the gender identity clinic of Amsterdam University Medical Centre in the Netherlands. Data of transgender people who received hormone treatment between 1972 and 2018 were linked to Statistics Netherlands. People were excluded if they used alternating testosterone and oestradiol treatment, if they started treatment younger than age 17 years, or if they had ever used puberty-blockers before gender-affirming hormone treatment. Standardised mortality ratios (SMRs) were calculated using general population mortality rates stratified by age, calendar period, and sex. Cause-specific mortality was also calculated. FINDINGS: Between 1972 and 2018, 8831 people visited the gender identity clinic. 4263 were excluded from the study for a variety of reasons, and 2927 transgender women and 1641 transgender men were included in the study, with a total follow-up time of 40 232 person-years for transgender women and 17 285 person-years for transgender men. During follow-up, 317 (10·8%) transgender women died, which was higher than expected compared with general population men (SMR 1·8, 95% CI 1·6-2·0) and general population women (SMR 2·8, 2·5-3·1). Cause-specific mortality in transgender women was high for cardiovascular disease, lung cancer, HIV-related disease, and suicide. In transgender men, 44 people (2·7%) died, which was higher than expected compared with general population women (SMR 1·8, 95% CI 1·3-2·4) but not general population men (SMR 1·2, 95% CI 0·9-1·6). Cause-specific death in transgender men was high for non-natural causes of death. No decreasing trend in mortality risk was observed over the five decades studied. INTERPRETATION: This observational study showed an increased mortality risk in transgender people using hormone treatment, regardless of treatment type. This increased mortality risk did not decrease over time. The cause-specific mortality risk because of lung cancer, cardiovascular disease, HIV-related disease, and suicide gives no indication to a specific effect of hormone treatment, but indicates that monitoring, optimising, and, if necessary, treating medical morbidities and lifestyle factors remain important in transgender health care. FUNDING: None.

Frequency and outcomes of benign breast biopsies in trans women: A nationwide cohort study.

No literature is available on the benign versus malignant breast lesion ratio in trans women (male sex assigned at birth, female gender identity). As hormone treatment in trans women results in breast tissue histologically comparable with cis (non-trans) women, breast pathology may be expected. Previously, an increased breast cancer risk compared with cis men have been observed. We aimed to investigate the frequency and outcomes of breast biopsies in trans women. Therefore, we retrospectively examined the medical files of 2616 trans women. To gain data on breast lesions, we linked our cohort to a national pathology database. In this study we found that 126 people (5%) had one or more breast biopsies (n = 139). Of these, 21 trans women had a breast biopsy before the start of hormone treatment, and 53 after the start of hormone treatment. Breast biopsies were performed predominantly because of abnormalities during physical examination (37%, n = 51/139 biopsies), or because of capsular formation or contraction (28%, n = 16/57 biopsies) in trans women with breast implants. The most common breast lesions after the start of hormone treatment were fibroadenomas (n = 20), breast cancer (n = 6), fibrosis (n = 5), cysts (n = 4), and infections (n = 4). The benign versus malignant breast biopsy ratio was 88:12, which is comparable to the ratio in cis women (90:10). This study shows breast lesions in a limited number of trans women. Since the indications and outcomes of biopsies in trans women were similar to those in cis women, it seems reasonable to follow breast care guidelines as developed for cis women.

Sustained Breast Development and Breast Anthropometric Changes in 3 Years of Gender-Affirming Hormone Treatment.

CONTEXT: Breast development is important for most trans women. An important limitation of current breast development measurement methods is that these do not allow for 3D volume analyses. OBJECTIVES: To examine breast development and change in anthropometry during the first 3 years of gender-affirming hormone treatment using 3D imaging. Associations with clinical or laboratory parameters and satisfaction with the gained breast development were also studied. DESIGN: Prospective cohort study. SETTING: Specialized tertiary gender identity clinic in Amsterdam, the Netherlands. PARTICIPANTS: Participants were 69 adult trans women with a median age of 26 years (interquartile range, 21-38). INTERVENTIONS: Gender-affirming hormone treatment. MAIN OUTCOME MEASURES: Volumetric and anthropometric breast development and satisfaction. RESULTS: Breast volume increased by 72 cc (95% confidence interval [CI], 48-97) to 100 cc (standard deviation 48). This resulted in a cup-size

[Hormone treatment of transgender people: Long-term health effects and safety]. / Hormoonbehandeling bij transgenderpersonen.

•Transgender people experience incongruence between the sex assigned at birth and the gender with which they identify. •Transgender people can be treated with sex hormones and gender-affirming surgery to induce desired physical changes of the gender they identify with. •Treatment with sex hormones is effective; it induces the desired physical characteristics and improves self-image. •Transgender women have a higher risk of venous thromboembolism, stroke and meningioma compared to cisgender men and cisgender women. Compared to cisgender men, transgender women have a higher risk of breast cancer and transgender women > 50 years old have a higher risk of fractures. •Transgender men have a higher risk of myocardial infarction than cisgender women. Their risk of fracture is just as high as that of cisgender women and their risk of breast cancer is lower. •Although hormone treatment is generally considered safe for transgender people, the risk of cardiovascular disease should definitely be carefully monitored. Transgender people should also be advised to participate in population screening programmes based on the organs they have.

Prostate Cancer Incidence under Androgen Deprivation: Nationwide Cohort Study in Trans Women Receiving Hormone Treatment.

CONTEXT: Trans women (male sex assigned at birth, female gender identity) mostly use antiandrogens combined with estrogens and can subsequently undergo vaginoplasty including orchiectomy. Because the prostate remains in situ after this procedure, trans women are still at risk for prostate cancer. OBJECTIVE: To assess the incidence of prostate cancer in trans women using hormone treatment. The incidence of prostate cancer in trans women using hormone treatment. DESIGN: In this nationwide retrospective cohort study, data of participants were linked to the Dutch national pathology database and to Statistics Netherlands to obtain data on prostate cancer diagnosis and mortality. SETTING: Gender identity clinic. PARTICIPANTS: Trans women who visited our clinic between 1972 and 2016 and received hormone treatment were included. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) were calculated using the number of observed prostate cancer cases in our cohort and the number of expected cases based on age-specific incidence numbers from the Netherlands Comprehensive Cancer Organization. RESULTS: The study population consisted of 2281 trans women with a median follow-up time of 14 years (interquartile range 7-24), and a total follow-up time of 37 117 years. Six prostate cancer cases were identified after a median 17 years of hormone treatment. This resulted in a lower prostate cancer risk in trans women than in Dutch reference males (SIR 0.20, 95% confidence interval 0.08-0.42). CONCLUSIONS: Trans women receiving androgen deprivation therapy and estrogens have a substantially lower risk for prostate cancer than the general male population. Our results support the hypothesis that androgen deprivation has a preventive effect on the initiation and development of prostate cancer.

Fracture Risk in Trans Women and Trans Men Using Long-Term Gender-Affirming Hormonal Treatment: A Nationwide Cohort Study.

Concerns about bone health in transgender people using gender-affirming hormonal treatment (HT) exist, but the fracture risk is not known. In this nationwide cohort study, we aimed to compare the fracture incidence in transgender people using long-term HT with an age-matched reference population. All adult transgender people who started HT before 2016 at our gender-identity clinic were included and were linked to a random population-based sample of 5 age-matched reference men and 5 age-matched reference women per person. Fracture incidence was determined using diagnoses from visits to hospital emergency rooms nationwide between 2013 and 2015. A total of 1089 trans women aged <50 years (mean 38 ± 9 years) and 934 trans women aged ≥50 years (mean 60 ± 8 years) using HT for median 8 (interquartile range [IQR] 3-16) and 19 (IQR 11-29) years, respectively, were included. A total of 2.4% of the trans women aged <50 years had a fracture, whereas 3.0% of the age-matched reference men (odds ratio [OR] = 0.78, 95% confidence interval [CI] 0.51-1.19) and 1.6% of the age-matched reference women (OR = 1.49, 95% CI 0.96-2.32) experienced a fracture. In trans women aged ≥50 years, 4.4% experienced a fracture compared with 2.4% of the age-matched reference men (OR = 1.90, 95% CI 1.32-2.74) and 4.2% of the age-matched reference women (OR = 1.05, 95% CI 0.75-1.49). A total of 1036 trans men (40 ± 14 years) using HT for median 9 (IQR 2-22) years were included. Fractures occurred in 1.7% of the trans men, 3.0% of the age-matched reference men (OR = 0.57, 95% CI 0.35-0.94), and 2.2% of the age-matched reference women (OR = 0.79, 95% CI 0.48-1.30). In conclusion, fracture risk was higher in older trans women compared with age-matched reference men. In young trans women, fracture risk tended to be increased compared with age-matched reference women. Fracture risk was not increased in young trans men. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Frequency, Determinants, and Satisfaction of Breast Augmentation in Trans Women Receiving Hormone Treatment.

INTRODUCTION: As breast development in trans women (male sex assigned at birth, female gender identity) who receive gender-affirming hormone treatment is often moderate, they may choose breast augmentation as part of their treatment. AIM: The aim of the study was to investigate the frequency, determinants, and satisfaction of breast augmentation among trans women receiving hormone treatment. METHODS: Trans women who started hormone treatment between 1972 and 2018 at our center received an anonymous questionnaire. MAIN OUTCOME MEASURE: The questionnaire contained questions about the start date of hormone treatment, the current age of the respondent, whether or not she underwent breast augmentation, what her considerations in this decision were, and, if the respondent did have breast implants, whether she was satisfied with the result and/or experienced health complaints she attributed to her breast implants. RESULTS: A total of 3,073 questionnaires were distributed, of which 773 were retrieved back (median age of the respondents: 50 years, interquartile range: 35-59). Age and year of start of hormone treatment was comparable between responders and nonresponders. The frequency of breast augmentation varied from 70% in trans women who started hormone treatment between 1980 and 2000 to 20% in those who started between 2010 and 2015. Trans women underwent breast augmentation median 2 years after the start of hormone treatment (interquartile range: 2-4), and 80% was satisfied with the result. Approximately one-third experienced health complaints they attributed to their breast implants. People who considered breast augmentation reported financial limitations as an important reason not to undergo breast augmentation. CLINICAL IMPLICATIONS: This study shows that it is important to discuss pros and cons of breast augmentation to support trans women in making a well-informed decision. STRENGTHS & LIMITATIONS: This is the largest study performed on the frequency and satisfaction of breast augmentation among trans women, which also includes health complaints and considerations in the decision whether or not to undergo breast augmentation. One of the limitations was that we were unable to link other clinical data. CONCLUSION: 4 of 5 trans women either chose or considered breast augmentation as part of their gender-affirming treatment. Most of the trans women who underwent breast augmentation were satisfied with the result, although approximately one-third experienced health complaints they attributed to their breast implants. Reasons not to undergo breast augmentation included financial limitations. This study shows that it is important to discuss with trans women the positive effects and possible side-effects of breast augmentation to help them make a well-informed decision whether or not to undergo breast augmentation. de Blok CJM, Staphorsius AS, Wiepjes CM, et al. Frequency, Determinants, and Satisfaction of Breast Augmentation in Trans Women Receiving Hormone Treatment. J Sex Med 2020;17:342-348.

Bone geometry and trabecular bone score in transgender people before and after short- and long-term hormonal treatment.

BACKGROUND: Gender-affirming hormonal treatment (HT) in adult transgender people influences bone mineral density (BMD). Besides BMD, bone geometry and trabecular bone score are associated with fracture risk. However, it is not known whether bone geometry and TBS changes during HT. PURPOSE: To investigate the bone geometry and TBS in adult transgender people at different time points, up to 25 years, of HT. METHODS: A total of 535 trans women and 473 trans men were included, who were divided into three groups at time of their DXA: 20-29 years, 30-39 years, and 40-59 years. Subsequently, each group was divided into different HT durations: baseline, or after 5, 15, or 25 years of HT. Hip structure analysis was performed to measure subperiosteal width, endocortical diameter, average cortical thickness, and section modulus. TBS was calculated based on lumbar spine DXA images. RESULTS: In trans women in all age groups and in young trans men, no differences were observed in periosteal width, endocortical diameter, average cortical thickness, and section modulus for different durations of HT. In trans men aged 40-59 years, subperiosteal width, endocortical diameter, and section modulus were slightly higher in the groups who were using HT compared to the (peri- or postmenopausal) baseline group. In younger trans women, TBS tended to be higher in those using HT compared to the baseline groups, and in older trans women TBS was higher in those using HT for 25 years versus baseline (+0.04, 95%CI +0.00; +0.08). In younger trans men, TBS tended to be lower in those who used HT compared to the baseline groups, and in older trans men TBS was lower in those using 5 years HT versus baseline (-0.05, 95%CI -0.08; -0.01). CONCLUSION: No differences in cortical bone geometry parameters were found during different HT-durations. TBS increased in trans women and decreased in trans men, indicating that estrogens have positive effects on TBS. These data may be helpful in determining what sex reference values for calculating T-scores and Z-scores in adult transgender people should be used.

Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands.

OBJECTIVE: To investigate the incidence and characteristics of breast cancer in transgender people in the Netherlands compared with the general Dutch population. DESIGN: Retrospective, nationwide cohort study. SETTING: Specialised tertiary gender clinic in Amsterdam, the Netherlands. PARTICIPANTS: 2260 adult trans women (male sex assigned at birth, female gender identity) and 1229 adult trans men (female sex assigned at birth, male gender identity) who received gender affirming hormone treatment. MAIN OUTCOME MEASURES: Incidence and characteristics (eg, histology, hormone receptor status) of breast cancer in transgender people. RESULTS: The total person time in this cohort was 33 991 years for trans women and 14 883 years for trans men. In the 2260 trans women in the cohort, 15 cases of invasive breast cancer were identified (median duration of hormone treatment 18 years, range 7-37 years). This was 46-fold higher than in cisgender men (standardised incidence ratio 46.7, 95% confidence interval 27.2 to 75.4) but lower than in cisgender women (0.3, 0.2 to 0.4). Most tumours were of ductal origin and oestrogen and progesterone receptor positive, and 8.3% were human epidermal growth factor 2 (HER2) positive. In 1229 trans men, four cases of invasive breast cancer were identified (median duration of hormone treatment 15 years, range 2-17 years). This was lower than expected compared with cisgender women (standardised incidence ratio 0.2, 95% confidence interval 0.1 to 0.5). CONCLUSIONS: This study showed an increased risk of breast cancer in trans women compared with cisgender men, and a lower risk in trans men compared with cisgender women. In trans women, the risk of breast cancer increased during a relatively short duration of hormone treatment and the characteristics of the breast cancer resembled a more female pattern. These results suggest that breast cancer screening guidelines for cisgender people are sufficient for transgender people using hormone treatment.

Cancer Risk in Transgender People.

Gender-affirming hormonal treatment (HT) in transgender people is considered safe in general, but the question regarding (long-term) risk on sex hormone-related cancer remains. Because the risk on certain types of cancer differs between men and women, and some of these differences are attributed to exposure to sex hormones, the cancer risk may be altered in transgender people receiving HT. Although reliable epidemiologic data are sparse, the available data will be discussed in this article. Furthermore, recommendations for cancer screening and prevention will be discussed as well as whether to withdraw HT at time of a cancer diagnosis.

Bone Safety During the First Ten Years of Gender-Affirming Hormonal Treatment in Transwomen and Transmen.

Concerns about the effects of gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender people exist, particularly regarding the decrease in estrogen concentrations in transmen. Although it is known that HT is safe for BMD in the short term, long-term follow-up studies are lacking. Therefore this study aimed to investigate the change in BMD during the first 10 years of HT, to determine whether HT is safe and if assessing BMD during HT is necessary. A follow-up study was performed in adult transgender people receiving HT at the VU University Medical Center Amsterdam between 1998 and 2016. People were included if they were HT naive and had a dual-energy X-ray absorptiometry (DXA) scan at the start of HT. Follow-up DXA scans performed after 2, 5, and/or 10 years of HT were used for analyses. The course of BMD of the lumbar spine during the first 10 years of HT was analyzed using multilevel analyses. A total of 711 transwomen (median age 35 years; IQR, 26 to 46 years) and 543 transmen (median age 25 years; IQR, 21 to 34 years) were included. Prior to the start of HT, 21.9% of transwomen and 4.3% of transmen had low BMD for age (Z-score < -2.0). In transwomen lumbar spine BMD did not change (+0.006; 95% CI, -0.005 to +0.017), but lumbar spine Z-score increased by +0.22 (95% CI, +0.12 to +0.32) after 10 years of HT. Also in transmen lumbar spine BMD did not change (+0.008; 95% CI, -0.004 to +0.019), but lumbar spine Z-score increased by +0.34 (95% CI, +0.23 to +0.45) after 10 years of HT. This study showed that HT does not have negative effects on BMD, indicating that regularly assessing BMD during HT is not necessary. However, a high percentage of low BMD was found prior to HT, especially in transwomen. Therefore, evaluation of BMD before start of HT may be considered. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Risk factors for developing capsular contracture in women after breast implant surgery: A systematic review of the literature.

BACKGROUND: Capsular contracture is the most frequent complication in breast augmentation or reconstruction with breast implants. The exact mechanism for this complication is not completely understood. Yet, it is most likely to be a multifactorial condition. Several patient-, surgery-, and implant-specific risk factors have been related to cause capsular contracture. This review aims to provide a clear overview of all risk factors for capsular contracture. METHODS: A systematic literature review was performed focusing on patient-, surgery-, and/or implant-related factors related to capsular contracture in breast implants. PubMed, Embase, and Wiley/Cochrane Library databases were searched for relevant articles published from inception up to October 20, 2016. The included studies were assessed for the following main variables: study characteristics, patient characteristics, indication for surgery, type of surgery, implant characteristics, and other characteristics. RESULTS: Data on the risk factors for the development of capsular contracture were retrieved from 40 studies. A presumptive increased risk in the development of capsular contracture is shown for the following variables: longer duration of follow-up, breast reconstructive surgery in patients with a history of breast cancer, subglandular implant placement, postoperative hematoma, and a textured implant surface. There is little, weak, or no evidence for the association of other factors with capsular contracture. This review also shows a large heterogeneity between studies and within the definition of capsular contracture. CONCLUSION: This review provides an overview of the relationship between patient-, surgery-, and implant-specific risk factors in the development of capsular contracture.