Metabolic Effects of Hormone Therapy in Transgender Patients

In This Article

Abstract and Introduction

Abstract

Objective: Transgender patients may seek hormone therapy to induce physical changes to simulate their expressed or experienced gender. However, many providers are uncomfortable prescribing transgender hormones due to fears over safety. The goal of this study was to determine if transgender hormone therapy with estrogen and spironolactone for male-to-female (MtF) patients or with testosterone for female-to-male (FtM) patients had adverse anthropomorphic or metabolic effects.

Methods: This retrospective chart review study analyzed changes over time for 33 MtF and 19 FtM endocrine clinic patients at an academic endocrine practice with follow-up for up to 18 months after hormone initiation.

Results: Compared to baseline labs obtained prior to the initiation of hormone therapy, significant changes for the MtF cohort included an increase in high-density lipoprotein (HDL) and decrease in creatinine; however, triglycerides did not show a statistically significant change. In the FtM cohort, there were significant increases in body mass index, creatinine, hemoglobin, and hematocrit. Although statistically significant, these changes were minimal for both cohorts.

Conclusion: In our practice, hormone therapy was found to be safe in this retrospective study.

Introduction

Transgender is an umbrella term for people whose gender identity and/or gender expression differs from their natal sex. According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, transgender individuals can be diagnosed with gender dysphoria, a term that describes the distress accompanying a marked difference in the expressed or experienced gender from their natal sex.^[1] Recently, there has been a dramatic increase in public awareness of transgender individuals due to mainstream media exposure of celebrities such as the athlete Caitlyn Jenner and Orange is the New Black actress Laverne Cox. The increased visibility may also increase the patient population size through educating people about the existence of gender dysphoria and treatment options. According to one estimate, transgender people comprise approximately 0.3% of the U.S. population.^[2] Therefore, it is vital to continue educating providers about the care and treatment of transgender individuals.

Individuals identifying as transgender often seek hormonal therapy. Estrogen, with or without the antiandrogenic effects of spironolactone, is prescribed for male-to-female (MtF) patients, and testosterone is prescribed for female-to-male (FtM) patients. The Endocrine Society published guidelines for the initiation and monitoring of transgender hormone therapy.^[3] This therapy is meant to induce physical changes to simulate the patient's desired gender. However, the use of estrogen and testosterone has metabolic side effects, and many providers are uncomfortable with the use of hormone therapy regardless of whether it is used in same gender (cisgender) or transgender populations, especially due to the lack of knowledgeable providers on appropriate treatment options for transgender patients.^[4] Risks associated with estrogen use include cancer risks, cardiovascular risks including thrombosis and hypertension, and weight changes, among others. The major risks associated with spironolactone include hyperkalemia and blood pressure effects, particularly if subjects have underlying renal or liver disease. Testosterone can increase the risk of cardiovascular disease, hypertension, and polycythemia; liver toxicity is more associated with oral than parenteral administration but remains a potential concern. Although transgender individuals are increasingly accessing the health care system to seek hormonal therapy, little is known regarding outcomes and prevalence of metabolic perturbations in the transcommunity. The primary goal of this study was to determine if transgender hormone therapy had any adverse anthropomorphic or metabolic effects in a "real-world" cohort.

Table 1. MtF Cohort Demographics ^a
n	33
Average age	31 (range: 16–56)
Ethnicity
White, non-Hispanic	64%
Hispanic	6%
Black/African American	6%
Not specified	24%
Have insurance
Yes	75%
No	25%
Have PCP
Yes	63%
No	37%
Currently smokes
Yes	9%
No	91%
Listed gender
Female	30%
Male	70%

Abbreviations: listed gender = gender currently on the electronic medical record, entry in concordance with state-assigned/legal gender; MtF = male to female; PCP = primary care physician.
^aData shown as average ± SEM or percent, as indicated.

Table 2. FtM Cohort Demographics ^a
n	19
Average age	27 (range: 19–47)
Ethnicity
White, non-Hispanic	89%
Hispanic	0%
Black/African American	0%
Not specified	11%
Have insurance
Yes	88%
No	12%
Have PCP
Yes	33%
No	67%
Currently smokes
Yes	35%
No	65%
Listed Gender
Male	26%
Female	74%

Abbreviations: FtM = female to male; listed gender = gender currently on the electronic medical record, entry in concordance with state-assigned/legal gender; PCP = primary care physician.
^aData shown as average ± SEM or percent, as indicated.

Table 3. Longitudinal Metabolic Data for the MtF Patient Population ^a
Parameter	Baseline	Visit 1 (3–6 months)	Visit 2 (6–18 months)
n	33	30	15
BMI (kg/m²)	28.8 ± 1.4	29.4 ± 1.5	27.7 ± 1.9
sBP (mm Hg)	131 ± 3	129 ± 2	125 ± 4
dBP (mm Hg)	82 ± 2	80 ± 2	77 ± 3
TC (mg/dL)	171 ± 7	176 ± 9	194 ± 10
HDL (mg/dL)	41 ± 2	47 ± 2^c	52 ± 5
LDL (mg/dL)	103 ± 6	106 ± 8	116 ± 12
TG (mg/dL)	130 ± 13	115 ± 11	134 ± 21
K (mmol/L)	4.09 ± 0.06	4.12 ± 0.07	4.22 ± 0.08
Creat (mg/dL)	0.90 ± 0.03	0.85 ± 0.03^b	0.83 ± 0.03
Ca (mg/dL)	9.5 ± 0.1	9.5 ± 0.1	9.6 ± 0.1
ALT (U/L)	27 ± 3	28 ± 3	24 ± 4
AST (U/L)	23 ± 1	22 ± 2	23 ± 3
Oral estrogen use (n, avg daily dose)	0	18 (56%), 1.44 mg/day	7 (50%), 1.71 mg/day
Estrogen use by patch (n, avg daily dose)	0	7 (22%), 0.1 mg/day	2 (14%), 0.1 mg/day
Estrogen use by injection (n, avg daily dose)	0	7 (22%), 1.21 mg/day	5 (36%), 1.18 mg/day
Spironolactone use (n, avg daily dose)	0	23, 104 mg/day	14, 114 mg/day

Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase; BMI = body mass index; Ca = calcium; Creat = creatinine; dBP = diastolic blood pressure; HDL = high-density lipoprotein; K = potassium; LDL = low-density lipoprotein; MtF = male to female; sBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides.
^aData shown are average ± SEM.
^b P<.05, ^c P<.01 using a paired t test compared to baseline visit.

Table 4. Longitudinal Metabolic Data for the FtM Patient Population ^a
Parameter	Baseline	Visit 1 (3–6 months)	Visit 2 (6–18 months)
n	19	16	10
BMI (kg/m²)	28.1 ± 2.1	30.1 ± 2.3^b	25.2 ± 2.1
sBP (mm Hg)	124 ± 4	133 ± 6	122 ± 5
dBP (mm Hg)	76 ± 2	77 ± 2	75 ± 4
TC (mg/dL)	162 ± 6	160 ± 8	168 ± 19
HDL (mg/dL)	54 ± 4	48 ± 3	48 ± 8
LDL (mg/dL)	89 ± 6	94 ± 7	102 ± 15
TG (mg/dL)	96 ± 16	87 ± 11	83 ± 17
Creat (mg/dL)	0.73 ± 0.03	0.87 ± 0.04^b	0.82 ± 0.04^c
Ca (mg/dL)	9.3 ± 0.1	9.3 ± 0.1	9.6 ± 0.2
ALT (U/L)	23 ± 3	19 ± 2	16 ± 1
AST (U/L)	29 ± 9	23 ± 3	22 ± 3
Hgb (g/dL)	13.4 ± 0.3	14.2 ± 0.4^b	15.2 ± 0.4^c
Hct (%)	39.8 ± 0.8	43.4 ± 1.1^c	45.9 ± 1.2^c
RBC (1 × 10¹²/L)	4.51 ± 0.10	4.89 ± 0.12^b	5.12 ± 0.17^b
Average daily testosterone dose	0	10.71 mg/day	11.36 mg/day

Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase; BMI = body mass index; Ca = calcium; Creat = creatinine; dBP = diastolic blood pressure; FtM = female to male; Hct = hematocrit; HDL = high-density lipoprotein; Hgb = hemoglobin; K = potassium; LDL = low-density lipoprotein; RBC = red blood cell count; sBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides.
^aData shown are average ± SEM.
^b P<.05, ^c P<.01 using a paired t test compared to baseline.

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Metabolic Effects of Hormone Therapy in Transgender Patients

Abstract and Introduction

Abstract

Introduction

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