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What Are the Risks of Transgender Hormone Therapy?

  • Authors: News Author: Nancy A. Melville; CME Author: Charles P. Vega, MD
  • CME / ABIM MOC / CE Released: 5/21/2021
  • Valid for credit through: 5/21/2022
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, endocrinologists, and other clinicians who treat and manage transgender patients.

The goal of this activity is to analyze the relationship between gender-affirming hormone therapy and blood pressure.

Upon completion of this activity, participants will:

  • Analyze the effect of gender-affirming hormone therapy on body mass index
  • Assess how gender-affirming hormone therapy might affect blood pressure
  • Outline implications for the healthcare team


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News Author

  • Nancy A. Melville

    Freelance writer, Medscape


    Disclosure: Nancy A. Melville has disclosed no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine
    Irvine, California


    Disclosure: Charles P. Vega, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: GlaxoSmithKline

Editor/CME Reviewer

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Stephanie Corder, ND, RN, CHCP, has disclosed no relevant financial relationships.

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  • Hazel Dennison, DNP, RN, FNP-BC, CHCP, CPHQ, CNE

    Associate Director, Accreditation and Compliance
    Medscape, LLC


    Disclosure: Hazel Dennison, DNP, RN, FNP-BC, CHCP, CPHQ, CNE, has disclosed no relevant financial relationships.

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What Are the Risks of Transgender Hormone Therapy?

Authors: News Author: Nancy A. Melville; CME Author: Charles P. Vega, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 5/21/2021

Valid for credit through: 5/21/2022


Clinical Context

More than a million people living in the United States identify as transgender, and gender-affirming hormone therapy (GAHT) is becoming a routine part of care in many primary care and specialty practices across America. But the long-term health implications of GAHT are largely unknown. One health domain that bears scrutiny is cardiovascular health, given the known metabolic effects of estrogen and testosterone. Although data on the direct effects of GAHT on coronary or cerebrovascular outcomes are lacking, Suppakitjanusant and colleagues previously assessed the potential effect of GAHT on weight gain. Their results were published in the July 2020 issue of the Journal of Clinical and Translational Endocrinology.[1]

The study was conducted as a retrospective review of 227 patients at a single US center. The durations of GAHT among transgender women and transgender men were 6.59 and 3.43 years, respectively. During an average follow-up period of 7 years, the researchers found that transgender women experienced a significant increase in body mass index (BMI) after the initiation of GAHT (mean increase, 0.125 kg/m2 for each quarter on continuing GAHT). There was less weight gain and a nonsignificant increase in BMI among transgender women who continued previous GAHT, and there was no effect of GAHT on the BMI of transgender men.

The current study uses a similar research model to evaluate the effects of GAHT on blood pressure among adults.

Study Synopsis and Perspective

Transgender people treated with GAHT show distinctive changes in blood pressure that begin soon after treatment initiation and do not subside during years of treatment, according to the largest and longest observational study to date to look at the issue.

"Many physicians may not be aware of the changes to blood pressure in trans patients who start hormone therapy," senior author Michael S. Irwig, MD, director of transgender medicine at Beth Israel Deaconess Medical Center in Boston, Massachusetts, told Medscape Medical News.

"The take-away message for physicians is to monitor blood pressure both before and after starting hormone therapy in transgender patients, as over a third of transgender individuals had stage 1 hypertension before starting hormone therapy and many had their blood pressure increase after starting hormone therapy."

Mean Blood Pressure Increases in Transgender Males, Decreases in Females

In the study, published this week in Hypertension, Katherine Banks, MD, from The George Washington School of Medicine & Health Sciences, Washington, DC, and colleagues, followed 470 transgender adult patients for up to 5 years.[2]

The mean systolic blood pressure levels in transgender female patients (male at birth) significantly decreased compared with baseline within a few months of them starting GAHT.

Conversely, the systolic blood pressure levels in transgender males (females at birth) who were treated with testosterone increased during the same period.

There were no significant changes in the groups in terms of diastolic blood pressure, consistent with other studies.

"Our study is the first to describe the time course of the [blood pressure] effects of GAHT and to compare the rates of elevated [blood pressure] and stage 1 and stage 2 hypertension using [blood pressure] readings from gender-diverse individuals pre- and post-GAHT," the authors note.

GAHT, which has been prescribed to transgender patients for more than 25 years, typically involves a combination of estrogen and an antiandrogen for males transitioning to female, whereas the therapy for those transitioning to male generally only involves testosterone.

The therapy has previously been linked to various cardiac effects, with evidence showing that transgender men have as much as a 5 times greater risk for heart attack vs cisgender women, the authors note.

Although the American Heart Association issued a 2020 Scientific Statement addressing the cardiovascular disease risk, evidence on the effects specifically on blood pressure in transgender patients has been inconsistent.[3]

For the new study, Banks and colleagues enrolled 247 transgender females and 223 transgender males who were treated between 2007 and 2015 at 2 medical centers in Washington, DC. Of the individuals, who had a mean age of 27.8, about 27% were non-White and 16% were Latinx.

They had blood pressure measurements taken at baseline and at follow-up clinical visits for up to 57 months after the initiation of GAHT.

During the follow-up period, the transgender females had decreases in mean systolic blood pressure of 4.0 mm Hg within 2 to 4 months of starting hormone therapy (P < .0001), and mean declines of 6.0 mm Hg were further observed at 11 to 21 months compared with baseline.

In transgender males, mean systolic blood pressure increased by 2.6 mm Hg at 2 to 4 months (P = .02), and by 2.9 mm Hg at 11 to 21 months after starting therapy.

Furthermore, "although the average increase in systolic blood pressure was 2.6 mm Hg in transgender men within 2 to 4 months, some patients had much higher increases," Dr Irwig noted.

As many as 40% of transgender men had stage 1 hypertension after 11 to 21 months of hormone therapy.

The blood pressure changes in transgender males and females were observed across all 3 racial/ethnic groups of Whites, Blacks, and Latinx, and the changes remained consistent throughout the entire follow-up period of approximately 5 years while hormone therapy was continued.

In addition to the changes after therapy initiation, the researchers note that more than one third of individuals in both groups had stage 1 hypertension even before starting hormone therapy.

The findings are a concern in light of "clear evidence linking hypertension and higher blood pressure with cardiovascular events such as stroke and heart attacks," Dr Irwig said.

Protective Effects for Transgender Females?

Transgender females showed as much as a 47% decrease in the prevalence of stage 2 hypertension, from 19% to 10%, within 2 to 4 months of treatment with GAHT (P = .001), and the rate declined further to 8% at 11 to 21 months, suggesting a protective effect of the treatment.

"The rate of stage 2 hypertension did drop in transgender feminine individuals, which could be protective and lower their risk for cardiovascular events," Dr Irwig said.

"This was not a surprise, as lowering testosterone and the use of spironolactone can lower blood pressure," he noted.

Exceptions in Both Groups

Of note, a sizable proportion of patients had blood pressure changes that were in fact the opposite of the patterns seen in the majority of their gender group.

Specifically, although 42% to 53% of the transgender females had systolic blood pressure readings at least 5 mm Hg lower than their baseline readings, up to 32% had increases of at least 5 mm Hg compared with their baseline readings.

Likewise, whereas 41% to 59% of transgender males had increases of at least 5 mm Hg compared with baseline, up to 35% had levels that were at least 5 mm Hg lower than baseline.

"It was a surprise that over a quarter of individuals had changes opposite to the mean changes," Dr Irwig said.

The differing blood pressure changes underscore that "more research is needed to determine which formulations of estrogen, testosterone, and antiandrogens are optimal regarding [blood pressure] and cardiovascular health, especially in older individuals," the authors note.

GAHT Formulations Differ

Various formulations for gender-affirming hormone regimens are available, including oral, transdermal, sublingual, and intramuscular preparations.

In the study, 77% to 91% of transgender males were receiving intramuscular testosterone injections, with the rest receiving transdermal formulations, and 92% of transgender female patients were started on oral estradiol, with mean doses generally increasing over time.

The study's results are consistent with evidence from other studies, with 7 of 8 involving transgender males showing mean increases in systolic blood pressure ranging from 1 to 14 mm Hg.

Previous Research Supports Cardiovascular Risk

As reported by Medscape Medical News, other emerging research on cardiovascular risks to transgender people include a recent study showing that more than 10% of transgender males were found to have hematocrit levels that could put them at risk for blood clots.[4,5]

And further research on transgender youth also shows concerning elevations in lipids and other cardiovascular risks.[6]

The authors have disclosed no relevant financial relationships.

Hypertension. Published online April 19, 2021.

Study Highlights

  • The study was conducted in a single urban community health center in Washington, DC. Patients eligible for chart review were at least 17 years of age and had noncisgender identity, and all had their baseline clinic visit between 2007 and 2015. All patients initiated GAHT at the clinic, and patients who had previously received GAHT during the 6 months before their clinic visit were included in the study.
  • The main study outcome was the change in blood pressure after initiation of GAHT. Researchers also followed incidence rates for stage 1 and stage 2 hypertension.
  • 247 trans feminine patients provided data for the study, along with 223 trans masculine patients. The mean age of patients was 27.8 years, and 27% were non-White; 16% of the sample was Latinx. 26.6% of subjects had a BMI of 30 kg/m2 or more at baseline, and 12% had stage 2 hypertension diagnosed before their baseline clinic visit. The mean initial blood pressure at that visit was 124.2/77.6 mm Hg.
  • Compared with trans feminine patients, trans masculine patients tended to be younger and have higher rates of obesity, but lower average systolic blood pressure and rates of hypertension.
  • Most trans feminine patients received 17β-estradiol, and more than 90% of these patients received spironolactone during the first 2 years of the study. More than 75% of trans masculine received intramuscular testosterone esters.
  • Within 2 to 4 months of the initiation of GAHT, mean systolic blood pressure was lower in the trans feminine group and higher in the trans masculine group.
  • The mean systolic blood pressure reduction in the trans feminine group was 4.0 mm Hg at 2 to 4 months and 6.0 mm Hg at 11 to 21 months. The respective increases in systolic blood pressure in the trans masculine group were 2.6 and 2.9 mm Hg.
  • There was no difference in the main study finding based on patient race/ethnicity.
  • Diastolic blood pressure was unaffected by GAHT.
  • 19% of the trans feminine group had stage 2 hypertension at baseline, but this value dropped to 10% at 2 to 4 months and 8% at 11 to 21 months. Rates of stage 2 hypertension were stable in the trans masculine cohort over time, but the rate of stage 1 hypertension increased from 33.3% at baseline to 39.9% at 11 to 21 months.
  • However, in examining individual patient data, approximately 25% of trans feminine and trans masculine patients experienced changes in their systolic blood pressure that were the opposite of what was true for their gender cohort. This reinforced the need to evaluate each patient individually for their blood pressure and risk for hypertension.

Clinical Implications

  • In a previous retrospective study, initiating GAHT among trans feminine patients was associated with a higher BMI, but transgender women who continued GAHT did not experience weight gain. GAHT did not affect the BMI of trans masculine patients.
  • In the current study, mean systolic blood pressure decreased with GAHT initiation in the trans feminine group, but it increased with GAHT in the trans masculine group.
  • Outline implications for the healthcare team: The healthcare team should bear in mind that GAHT may reduce systolic blood pressure among trans feminine patients, but GAHT may raise systolic blood pressure among trans masculine patients.


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