Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People

Shadid, Samyah; Abosi-Appeadu, Kessewa; Maertelaere, Anne-Sophie De; Defreyne, Justine; Laurens, Véronique; Holst, Jens J.; Lapauw, Bruno; Vilsbøll, Tina; T’Sjoen, Guy

doi:10.2337/dc19-1061

Cited by 57 publications

(68 citation statements)

References 43 publications

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“…40 Moreover, testosterone also inhibits lipoprotein lipase activity in adipocytes, an enzyme that increases fat deposition by decreasing adipose tissue lipolysis. 14 We found no significant difference in insulin resistance between trans men and cisgender female controls, in keeping with all but one prior study in transgender men that showed either no cha nge [27][28][29][31][32][33][34][35][36][37]41 or a decrease 30,39 in insulin resistance. All these studies were prospective longitudinal in design but only one had a control group.…”

Section: Masculinising Hormone Therapysupporting

confidence: 85%

Insulin resistance in transgender individuals correlates with android fat mass

Bretherton

Spanos

Leemaqz

et al. 2021

Therapeutic Advances in Endocrinology

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Background: Transgender individuals receiving gender-affirming hormone therapy (GAHT) are at increased risk of adverse cardiovascular outcomes. This may be related to effects on body composition and insulin resistance. Aims: To examine relationships between body fat distribution and insulin resistance in transgender individuals on established GAHT. Methods: Comparisons of body composition (dual energy X-ray absorptiometry) and insulin resistance [Homeostasis Model of Insulin Resistance (HOMA2-IR)] were made between transgender individuals (43 trans men and 41 trans women) on established GAHT (>12 months) and age-matched cisgender controls (30 males and 48 females). Multiple linear regressions were used to examine the relationship between HOMA2-IR and fat mass with gender, adjusting for age and total duration of GAHT and Pearson correlation coefficients are reported. Results: Compared with control cisgender women, trans men had mean difference of +7.8 kg (4.0, 11.5), p < 0.001 in lean mass and higher android:gynoid fat ratio [0.2 (0.1, 0.3), p < 0.001], but no difference in overall fat mass or insulin resistance. Compared with control cisgender men, trans women had median difference in lean mass of −6.9 kg (–10.6, –3.1), p < 0.001, fat mass of +9.8 kg (3.9, 14.5), p = 0.001, lower android:gynoid fat ratio −0.1 (–0.2,–0.0), p < 0.05), and higher insulin resistance 1.6 (1.3–1.9), p < 0.001). Higher HOMA2-IR correlated with higher android ( r2 = 0.712, p < 0.001) and gynoid ( r2 = 0.572, p < 0.001) fat mass in both trans men and trans women. Conclusion: Android fat more strongly correlates with insulin resistance than gynoid fat in transgender individuals. Higher fat mass and insulin resistance in trans women may predispose to increased cardiovascular risk. Despite adverse fat distribution, insulin resistance was not higher in trans men.

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Section: Masculinising Hormone Therapysupporting

confidence: 85%

Insulin resistance in transgender individuals correlates with android fat mass

Bretherton

Spanos

Leemaqz

et al. 2021

Therapeutic Advances in Endocrinology

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“…We have demonstrated remarkable responses (clinical exam, mammography, ultrasound) of hormone receptor positive tumors to T + aromatase inhibitor implant therapy in the neoadjuvant setting, further confirming the direct beneficial effect of T at the AR [8,9]. T also improves glycemic control and attenuates the inflammatory process, both of which could have a beneficial effect on the incidence of breast cancer [14,15,32,33].…”

Section: Discussionsupporting

confidence: 58%

“…Most notably, in our patient population, mean serum T level when symptoms returned (trough) was 171 + 73 ng/dl, well above endogenous ranges, with significant inter-individual variation (CV 42.6%). In regard to safety, long-term studies on transgender men have shown that even higher (male) doses of T do not increase the risk of cardiovascular events, stroke, or cancer; T therapy also increases insulin sensitivity, as opposed to estrogen therapy in transgender women [32,37,38]. No other hormone medication (e.g., insulin, estrogen) is dosed or micromanaged based solely on levels of the active pharmacologic ingredient in serum, but rather on clinical response/beneficial effects versus adverse side effects.…”

Section: Discussionmentioning

confidence: 99%

Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study

2019

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Background: Testosterone implants have been used for over eighty years to treat symptoms of hormone deficiency in pre and postmenopausal women. Evidence supports that androgens are breast protective. However, there is a lack of data on the long-term effect of testosterone therapy on the incidence of invasive breast cancer (IBC). This study was specifically designed to investigate the incidence of IBC in pre and postmenopausal women (presenting with symptoms of androgen deficiency) treated with subcutaneous testosterone implants or testosterone implants combined with anastrozole. Methods: The 10-year prospective cohort study was approved in March 2008 at which time recruitment was initiated. Recruitment was closed March 2013. Pre and postmenopausal women receiving at least two pellet insertions were eligible for analysis (N = 1267). Breast cancer incidence rates were reported as an unadjusted, un-weighted value of newly diagnosed cases divided by the sum of 'person-time of observation' for the at-risk population. Incidence rates on testosterone therapy were compared to age-specific Surveillance Epidemiology and End Results (SEER) incidence rates and historical controls. Bootstrap sampling distributions were constructed to verify comparisons and tests of significance that existed between our results and SEER data. Results: As of March 2018, a total of 11 (versus 18 expected) cases of IBC were diagnosed in patients within 240-days following their last testosterone insertion equating to an incidence rate of 165/100000 p-y, which is significantly less than the age-matched SEER expected incidence rate of 271/100000 p-y (p < 0.001) and historical controls. Conclusion: Long term therapy with subcutaneous testosterone, or testosterone combined with anastrozole, did not increase the incidence of IBC. Testosterone should be further investigated for hormone therapy and breast cancer prevention.

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“…The increases in body weight, particularly fat mass, in transgender women may explain why GAHT is associated with increased CVA and CVD in transgender women but not in transgender men [12] . Increases in fat mass in transgender women as compared to transgender men may also predispose transgender women to increased risk of metabolic syndrome [13] , [14] .…”

Section: Introductionmentioning

confidence: 99%

Effects of gender affirming hormone therapy on body mass index in transgender individuals: A longitudinal cohort study

Suppakitjanusant

Stevenson

et al. 2020

Journal of Clinical & Translational Endocrinology

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Introduction Many transgender people take hormone therapy to affirm their gender identity. One potential long-term consequence of gender affirming hormone therapy is increased body mass index (BMI), which may be associated with metabolic syndrome, cardiovascular disease and higher mortality. Only a few published studies explored changes in BMI in transgender people taking gender affirming hormone therapy (GAHT). Objective To examine the changes in BMI longitudinally in response to GAHT in transgender women and men. Methods We conducted a retrospective cohort study of transgender individuals who received GAHT from the endocrinology clinic between January 1, 2000 and September 6, 2018. Subjects who sought GAHT were included if they had two separate measurements of BMI and were excluded if they had a BMI greater than 35 kg/m 2 or were missing demographic data at entry. We used a linear mixed model to analyze the longitudinal change in BMI. Results There were a total of 227 subjects included in this cohort. Among subjects already on GAHT, transgender women were receiving GAHT longer than transgender men (6.59 ± 9.35 vs 3.67 ± 3.43 years, p-value = 0.04). Over the period of 7 years, there was a significant increase in BMI in transwomen who newly initiated GAHT (p-value 0.004). There were no changes in BMI in transgender men and women already on GAHT or in transgender men who newly initiated GAHT in the study. Conclusion We conclude that BMI significantly increases in transwomen but not in transmen after initiation of GAHT in a single center based in the United States. In transwomen and transmen, BMI appears to be stable following 3 to 6 years of GAHT. Future investigations should examine the causes for increased BMI in transgender women including type of GAHT, diet and lifestyle, and association with risk of metabolic syndrome and cardiovascular disease.

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Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People

Cited by 57 publications

References 43 publications

Insulin resistance in transgender individuals correlates with android fat mass

Insulin resistance in transgender individuals correlates with android fat mass

Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study

Effects of gender affirming hormone therapy on body mass index in transgender individuals: A longitudinal cohort study

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