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Zil Goldstein,1 Musaub Khan,2 Tamar Reisman,1 Joshua D Safer11Center for Transgender Medicine and Surgery at Mount Sinai, Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; 2New York Medical College, Valhalla, NY USAIntroduction: Venous thromboembolism (VTE) is a potential risk of estrogen therapy. However, data show an improvement in the quality of life for transgender people who use feminizing hormone therapy. With few transgender-specific data, guidance may be drawn from cisgender (nontransgender) data, with a focus on hormonal birth control and postmenopausal hormone replacement therapy (HRT). The aim of this review is to examine the degree to which routes of administration, patient comorbidities, and type of hormone utilized affect the safety of estrogen therapy.Methods: We identified 6,349 studies by searching PubMed with the terms “transgender”, “estrogen”, “VTE”, and “HRT”. Of these, there were only 13 studies between 1989 and 2018 that investigated the effects of hormone therapy, including types of estrogens used, in transgender women and men.Results: The data suggest that the route of hormone administration, patient demographics, and patient comorbidities all affect estrogen’s link with VTE. For example, avoiding ethinyl estradiol might make the use of hormone therapy in trans feminine individuals safer than oral birth control. Data from both cis and trans groups suggest additional VTE risk associated with the use of progestins. While transdermal estrogens dosed up to 0.1 mg/day or below appear lower risk for VTE than other forms of estrogen, it is unclear whether this is related to the delivery method or a dose effect. Finally, even if the risk from exogenous estrogen use remains significant statistically, the absolute clinical risk remains low.Conclusion: Clinicians should avoid the use of ethinyl estradiol. Additionally, data suggest that progestins should be avoided for transgender individuals. Further study of the relationship between estrogen use and the risk of VTE will serve to inform the safest care strategies for transgender individuals.Keywords: transgender, estrogen therapy, venous thromboembolism

Objective: To review he impact of estrogen-containing feminizing hormone regimens on transgender individuals' risk for VTE., Methods: We evaluated VTE risk by screening 1170 relevant studies published from 1994 to 2020, focusing on meta-analysis data., Results: The type of oral estrogen, route of administration, patient demographics, and comorbidities may affect the risk of VTE. Venous thrombosis is the most common vascular complication associated with HT., Conclusion: Conjugated equine estrogens and 17-β estradiol appear to be safer than oral ethinyl estradiol. Transdermal estrogen formulations appear to be the least thrombogenic estrogens. Estrogens used concomitantly with progestins increase the risk of VTE compared to estrogens alone. To date, there are no data to demonstrate the benefit of holding HT prior to vaginoplasty or other gender affirming surgeries. For most young, healthy transgender women, there is little risk of VTE with HT, while older patients with risk factors should be discussed case by case., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: Transgender and gender-nonbinary individuals (TGNB) are disproportionately impacted by obesity. In addition to the associated health impact, obesity represents a significant barrier to accessing gender-confirmation surgery (GCS). The purpose of this study was to determine the prevalence of obesity among TGNB surgical candidates at an urban academic medical center and evaluate the efficacy of self-monitored weight management. Methods: The study was conducted at the Center for Transgender Medicine and Surgery at Mount Sinai in New York City. Data abstraction from a quality improvement database was completed for patients with a documented body mass index (BMI) and a GCS consult from October 2015 through February 2019. A total of 1,457 TGNB patients with a documented BMI and a GCS consult in the historical period of review were included in analysis. Data were abstracted to determine the prevalence of obesity among GCS candidates and evaluate the current default pre-operative self-monitored weight management protocol. Results: Of 1,457 TGNB patients, 382 (26%) were obese (BMI ≥30 kg/m 2 ) at initial surgical consult. In addition, 369 (27%) were obese at a subsequent follow-up, suggesting no statistically significant change in the rate of obesity among evaluated TGNB despite self-monitored weight management ( P = .5272). Conclusion: Obesity is a significant barrier to gender affirming surgery for transgender individuals. Self-monitored weight management is an unsuccessful strategy for improvement even among individuals who would be predicted to be motivated. Abbreviations: BMI = body mass index; CTMS = Center for Transgender Medicine and Surgery (at Mount Sinai); GCS = gender confirmation surgery; TGNB = transgender and gender-nonbinary.

Objective: The objective of this article is to describe the hormonal pathways required for breast development in cisgender women and to review the current available literature describing breast growth and breast cancer risk in transgender women. Methods: Literature review and discussion. Results: Early mammary tissue development occurs prenatally. This process is hormone-independent and occurs similarly in males and females. Breast tissue is quiescent until puberty, at which time surging estrogen levels in cisgender girls mediate breast development and growth. Adult breast tissue composition further evolves in cisgender women during pregnancy, lactation, and menopause, revealing the ever-changing interplay between breast structure and hormonal environment. Conclusion: Breast growth is a significant physical endpoint in the hormonal treatment of transgender women. Transgender hormone regimens, which typically pair an estrogen with an anti-androgen, can help achieve this goal.

Background: Levothyroxine is the most commonly prescribed medication in the United States. Many foods and medications, including calcium supplements, can interfere with levothyroxine absorption. No studies have investigated the effect of cow's milk, a common breakfast staple, on the absorption of oral levothyroxine. Cow's milk contains approximately 450 mg of elemental calcium per 12 oz (355 mL) serving., Methods: A pharmacokinetic study was conducted in healthy euthyroid subjects to assess levothyroxine absorption with and without concurrent cow's milk consumption. Following an overnight fast, serum total thyroxine (TT4) concentrations were measured at baseline and at one, two, four, and six hours after ingestion of 1000 μg of oral levothyroxine alone or when co-administered with 12 oz (355 mL) of 2% milk. There was a four-week washout period between the two assessments in each subject., Results: Ten subjects (M age  ± SD = 33.7 ± 10.2 years; 60% male) completed the study. The area under the curve (AUC) of TT4 concentrations was significantly lower when levothyroxine was ingested along with 12 oz (355 mL) of 2% cow's milk (M ± SD = 67.3 ± 12.1) compared to that with levothyroxine alone (73.5 ± 17.0; p = 0.02). Also, peak serum TT4 concentrations were significantly lower when cow's milk was co-administered with levothyroxine (M ± SD = 14.1 ± 0.8 μg/dL) than with levothyroxine alone (13.0 ± 0.9 μg/dL; p = 0.04)., Conclusions: This is the first study to demonstrate that concurrent cow's milk ingestion reduces oral levothyroxine absorption. The findings support previous literature showing the interference of elemental calcium and food with thyroid hormone absorption. Patients managed with thyroid hormone should be advised to avoid taking their levothyroxine simultaneously with cow's milk.

Objective: Our report describes a case of nonpuerperal induced lactation in a transgender woman. Methods: We present the relevant clinical and laboratory findings, along with a review of the relevant literature. Results: A 30-year-old transgender woman who had been receiving feminizing hormone therapy for the past 6 years presented to our clinic with the goal of being able to breastfeed her adopted infant. After implementing a regimen of domperidone, estradiol, progesterone, and breast pumping, she was able to achieve sufficient breast milk volume to be the sole source of nourishment for her child for 6 weeks. This case illustrates that, in some circumstances, modest but functional lactation can be induced in transgender women., Competing Interests: No competing financial interests exist.

Purpose: This review will inform radiologists about the evidence base regarding radiographic imaging for transgender individuals and considerations for providing culturally sensitive care for this population., Findings: Transgender individuals are increasingly referred for both screening and diagnostic breast imaging. It is important that the clinic environment is welcoming, the medical staff utilize accepted terminology and patients are able to designate their gender and personal history to ensure appropriate care. Hormone and surgical treatments used for transition by many transgender women and men may change the approach to imaging., Summary: Although not yet evidence-based, screening mammography is currently suggested for transgender women with risk factors, including those receiving hormone treatment over 5 years. The risk for breast cancer in transgender individuals is still being defined., Competing Interests: Compliance with Ethical StandardsEmily B. Sonnenblick, Ami D. Shah, Zil Goldstein, and Tamar Reisman each declare no potential conflicts of interest.This article does not contain any studies with human or animal subjects performed by any of the authors.