Transgender Hormone Therapy Is Safe When Monitored For Certain Risks

One of the most often cited reasons by medical providers for hesitation in providing hormone therapy to transgender individuals is the fear of harm. The review demonstrates that hormone therapy is relatively safe, at least as far as the modest literature out there can determine. Providers should be reassured that the harms that do exist are relatively rare and can often be avoided with conventional monitoring.

The take-home points from the review are:

1.  The current literature suggests that transgender hormone therapy is safe for most situations and reasonable to monitor.

2.  The current literature is quite thin, and larger, more carefully done studies are needed to address concern for more subtle harms.

The findings align with the hormone approach found in both the World Professional Association for Transgender Health (WPATH) Standards of Care of 2011 and The Endocrine Society Guidelines of 2009. The primary difference between this review and the 2 guidelines is the failure to detect increased cancer risk despite the concerns raised in the guidelines.

Use of hormone therapy in transgender adults is considered safe when carefully monitored for certain risks, such as venous thromboembolism (VTE) in transgender women with use of estrogen therapy, according to a literature review published in the February 24 issue of the Journal of Clinical and Translational Endocrinology. The findings may help reduce the barriers for transgender individuals to receive medical care.

Although many of the studies identified in the literature review involved a small number of patients or were case studies, the overall trend of the findings is reassuring. Notably, while some guidelines on transgender medical care suggest that certain hormone therapies increase the risk for cancer, no evidence of a significant increase in cancer risk was found in this literature review. In addition, hormone therapy was not linked to increased mortality in transgender individuals.

The review included papers from an original pool of 1,881 studies published between 1967 and 2014 that assessed the safety of hormone therapy for transgender individuals. Case reports were included when there was a lack of long-term studies on a given safety issue.  

Increased Risk of Venous Thromboembolism With Estrogen Therapy
The primary concern with use of hormone therapy in transgender women is the risk for VTE associated with estrogen therapy. In one of the largest and most recent studies, Asscheman et al found that 1% of 1,076 transgender women taking estrogen therapy experienced VTE.1 Other studies suggest that the risk for VTE is higher (6%-8%) in individuals taking ethinyl oestradiol, which is no longer in use.2

Risk factors for VTE found in a study by Gooren et al of 2,236 transgender women included smoking, immobilization due to gender confirmation surgery, and presence of a hypercoagulable disorder.3

Other studies suggest that the risk for VTE and other cardiovascular events is less with use of transdermal estrogen versus oral estrogen. Treatment of hypercholesterolemia and hypertension, and smoking cessation may help minimize the risk for VTE among transgender men.

Cancer Prevalence Is Not Increased in Transgender Adults Using Hormone Therapy
The overall cancer incidence in transgender men and women did not differ significantly from that in control groups in studies to date. The incidence of breast cancer in transgender individuals taking estrogen is not different from secular trends in males and is lower than secular trends in women. A rare but possible increase prostate cancer (0.04%) has been reported in transgender women, however, the findings are limited by decreased screening and the relative young age (average, 29.3 years) in subjects at the start of therapy.4

Hyperplasia in the female reproductive tract has been reported in studies that are low powered. However, newer data suggest that testosterone therapy in transgender men may be associated with tissue atrophy of the epithelium of the cervix and endometrium, not with malignancy as might have been presumed from the hyperplasia data.

It is also important to follow cancer screening guidelines for transgender individuals’ natal gender. 

Mortality Rates Not Altered by Transgender Hormone Therapy Use
Transgender hormone therapy does not have a direct affect on mortality, according to the 3 largest studies to date. While one study found a 51% increase in mortality in transgender women compared to secular data, the differences were linked to factors unrelated to hormone therapy, including an increased incidence of suicide, AIDS, substance abuse, and cardiovascular disease.5

Estrogen Therapy May Increase Triglyceride Levels and Insulin Resistance
Elevated triglyceride levels and decreased LDL cholesterol levels have been found in transgender women taking estrogen therapy compared to control subjects. In contrast, it is unclear from the current literature whether transgender men experience changes in these laboratory values.

Increases in insulin resistance and fasting glucose level, as well as changes in body fat redistribution were found in both transgender men and women. In addition, slight increases in hemoglobin and hematocrit were found among transgender men.

Finally, there is some evidence that hormone therapy in transgender women may lead to decreased sexual desire, but may lead to increased sexual desire in transgender men.

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