Blood pressure development in adolescents diagnosed with gender dysphoria assigned male at birth treated with gonadotropin-releasing hormone analogues and gender affirming hormones

Adolescents diagnosed with gender dysphoria (GD) are treated with gonadotropin-releasing hormones analogues (GnRHa) from age 11 and subsequently gender affirming hormones (GAH) are added from the age of 16. Overall, this... [ view full abstract ]

Adolescents diagnosed with gender dysphoria (GD) are treated with gonadotropin-releasing hormones analogues (GnRHa) from age 11 and subsequently gender affirming hormones (GAH) are added from the age of 16. Overall, this treatment is considered safe with respect to short-term effects. However, the occurrence of arterial hypertension has been reported in adolescent natal girls with GD (Klink et al., Int J Endocrinol Metab, 2015). In addition, it was shown that using 24-hour ambulatory blood pressure monitoring (ABPM) in adolescent natal girls with GD both nocturnal systolic (SBP) and diastolic blood pressure (DBP) increased during GnRHa monotherapy (Klink et al., EPATH, 2015) and that the addition of androgens increased both diurnal and nocturnal SBP (Bosman et al., WPATH, 2016). The effect of GnRHa monotherapy in adolescent natal boys remained unclear and the effect of estrogens has not been studied yet.

This study aimed to determine the effect of endocrine treatment on blood pressure in adolescent natal boys diagnosed with GD. [ view full abstract ]

This study aimed to determine the effect of endocrine treatment on blood pressure in adolescent natal boys diagnosed with GD.

Adolescent natal boys diagnosed with GD (transgirls) at VU University Medical Center who were eligible for treatment were included for participation after signing the informed consent form. Exclusion criteria were:... [ view full abstract ]

Adolescent natal boys diagnosed with GD (transgirls) at VU University Medical Center who were eligible for treatment were included for participation after signing the informed consent form. Exclusion criteria were: pre-existent hypertension, cardiac disease or kidney-disease with diminished renal function.
ABPM were performed 1) at start GnRHa, 2) during 6 to 12 months of GnRHa monotherapy, 3) prior to the addition of GAH (17-beta estradiol) and 4) during 12 months of GAH treatment. Mean 24-h, diurnal and nocturnal systolic and diastolic blood pressure were converted to standard deviation scores (SDS) and corrected for natal or desired sex and height (Wuhl et al., J hypertension, 2002). Statistical analysis was performed with SPSS. Data are presented as median [interquartile range] and compared using the Wilcoxon signed rank test.

SDS of 24-h, diurnal and nocturnal SBP and DBP (corrected for height and natal sex or height and desired sex) during GnRHa monotherapy or during GAH therapy. [ view full abstract ]

SDS of 24-h, diurnal and nocturnal SBP and DBP (corrected for height and natal sex or height and desired sex) during GnRHa monotherapy or during GAH therapy.

In 38 transgirls (median age 13.3 years [3.3]) ABPM was measured prior to start of GnRHa and during a median duration of GnRHa monotherapy of 11.5 months [4.0]. SDS (corrected for height and natal sex) of 24-h SBP and 24-h DBP... [ view full abstract ]

In 38 transgirls (median age 13.3 years [3.3]) ABPM was measured prior to start of GnRHa and during a median duration of GnRHa monotherapy of 11.5 months [4.0]. SDS (corrected for height and natal sex) of 24-h SBP and 24-h DBP did not change (-0.15 [1.8] vs. -0.35 [1.6]; p=0.57 and -0.95 [2.5] vs. -0.6 [2.1]; p= 0.17, respectively).

In 22 transgirls (median age 16.0 years [1.0]) ABPM was measured prior to the addition of GAH and during a median duration of estrogen therapy of 11.0 months [2.5]. 24-h SBP SDS and 24-h DBP SDS corrected for height and natal sex did not change (-0.6 [1.4] vs. -0.4 [1.8]; p=0.39 and -0.35 [1.6] vs. -0.05 [1.9]; p=0.65, respectively). However, when corrected for height and desired sex 24-h SBP increased (-0.6 [1.4] vs. 0.25 [2.3]; p=0.04) due to an increase in nocturnal SBP SDS (0.65 [1.5] vs. 0.9 [2.6]; p=0.02), while diurnal SBP SDS did not change (-0.9 [1.3] vs. -0.25 [2.1]; p=0.22).

BP did not change during GnRHa monotherapy in transgirls. Since androgens are known to have a BP elevating effect (Reckelhoff, Hypertension, 2001), the gonadal suppression would have been expected to lower BP. This discrepancy... [ view full abstract ]

BP did not change during GnRHa monotherapy in transgirls. Since androgens are known to have a BP elevating effect (Reckelhoff, Hypertension, 2001), the gonadal suppression would have been expected to lower BP. This discrepancy may be explained by the fact that gonadal suppression was started at an early pubertal stage when virilization was not yet advanced thus masking a BP lowering effect.

Estrogens on the other hand have BP lowering properties (Hinojosa-Laborde et al., Hypertension, 2001) but when compared to their natal (i.e. male) sex peers BP did not decrease in transgirls. In contrast, when compared to their desired sex peers nocturnal SBP increased. Estrogen response depends on hormone levels, but also on tissue sensitivity and intrinsic factors like the 46 XY karyotype; these factors may contribute to the modulation of the response to estrogens in transgirls.

Our data suggest that in contrast to transboys the endocrine treatment of transgirls has much milder effects on BP. However, continuing follow-up is needed to establish long-term effects and safety.