Benefits of gender-affirming HT outweigh risks for most transgender women
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The benefits of gender-affirming hormone therapy outweigh the risks for transgender women of all ages as well as those with comorbidities, according to a speaker at the 2022 North American Menopause Society annual meeting.
“Clinicians should use a shared decision-making approach when discussing if and how to adjust HT as transgender patients age,” Sarah Pickle, MD, associate professor in the department of family and community medicine at the University of Cincinnati College of Medicine, told Healio. “We should address with our patients how to decrease risk for cardiovascular disease, screen for breast cancer and osteoporosis, and recognize that gender-affirming hormones can improve outcomes in multiple areas of patient health.”
According to data from the Williams Institute at the UCLA School of Law, there are about 1.3 million transgender adults living in the U.S. today. Within that population, the use of gender-affirming hormones is common. About 71% of transgender women use or report intent to use gender-affirming HT. Additionally, 23% of transgender women begin using gender-affirming hormones after age 40 years, and 12% begin their use after age 50 years.
“Gender-affirming hormone regimens before 2000 often used ethinyl estradiol, which is more thrombogenic, leading to higher rates of venous thromboembolism,” Pickle said. “The recommended estradiol for gender-affirming hormones is now 17-beta estradiol, which contemporary studies suggest offers an improved safety profile.”
17-beta estradiol comes in several different delivery methods, including oral, patches and intramuscular. Target hormone ranges vary by patient, but serum estradiol should not exceed 100 pg/mL to 200 pg/mL, and serum testosterone should be less than 50 ng/dL.
A shared decision-making approach is key to successful HT for transgender women, according to Pickle. There is no evidence that supports stopping HT based on age alone, and any decisions should be based on a patient’s quality of life, expectations and coexisting medical conditions.
Gender-affirming HT and CV risk
There are some risks gender-affirming HT may present to transgender women that providers should be aware of. Transgender women taking oral estradiol have twice the risk for VTE as cisgender women or men. In addition, the risk for VTE increases over time. Transgender women aged 45 years or older and those with CV risk should use a transdermal estradiol instead of an oral formulation.
Transgender women using estradiol also have a twofold higher risk for myocardial infarction compared with cisgender women, though the risk is not significantly greater compared with cisgender men. The risk for ischemic stroke is also higher among transgender women using estradiol compared with cisgender adults, and the risk gradually increases over time.
“The risk of CV events in transgender patients is a story much bigger than estradiol,” Pickle said. “Estradiol is one of many factors in a dynamic landscape of CV risk, including other possible medical conditions like hypertension, hyperlipidemia, diabetes and HIV; as well as behaviors, including nutrition, movement, alcohol, other substances and sleep. The psychologic experience of other mental health conditions, interpersonal stigma, societal and system-level stigma, discrimination and violence that many transgender persons face can all create physiologic stress that impact CV risk as well. Thus, in the office, addressing CVD must include a holistic approach, including how gender-affirming hormones may help improve outcomes in other areas, like mental health and safety.”
Estradiol’s effect on breast cancer risk, bone health
Research has revealed mixed outcomes for breast cancer risk. Transgender women using estradiol have a lower risk for breast cancer than cisgender women, but a higher risk compared with cisgender men. Pickle said recommendations from multiple organizations support breast cancer screening for transgender women taking HT, though organizations are not in agreement as to when screening should begin.
Gender-affirming HT supports bone formation. Multiple studies have found transgender women using HT have higher bone mineral density at the lumbar spine, total hip and femoral neck than those not using HT. HT use and undergoing a gonadectomy can impact fracture risk.
Recommendations for osteoporosis screening using DXA include all transgender women at age 65 years, those who are at increased risk based on other medical conditions between age 50 and 64 years, and those who have had a gonadectomy and who are not using HT after 5 years,” Pickle said.
More research is needed analyzing the effects of gender-affirming HT on transgender women, according to Pickle. Future research should focus on target hormone levels in older adults, better methods to assess CV risk in transgender women, the dosing effect of estradiol on risk, and how the route and duration of HT may impact breast cancer risk.
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Pickle S. Plenary symposium 2. Presented at: North American Menopause Society Annual Meeting; Oct. 12-15, 2022; Atlanta.
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