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Health-related quality of life in acromegalic subjects: data from AcroBel, the Belgian Registry on acromegaly

Guy T’Sjoen, Marie Bex, Dominique Maiter, Brigitte Velkeniers, and Roger Abs

Objective: To assess the impairment of quality of life (QoL), evaluated by the acromegaly QoL (AcroQoL) questionnaire, in patients with controlled and uncontrolled acromegaly.

Design: Cross-sectional evaluation of AcroBel, a national observational registry of acromegalic patients newly diagnosed or in follow-up.

Methods: Disease perception by the patients was evaluated by the disease-specific signs and symptoms score (SSS) and QoL was assessed by the AcroQoL questionnaire. Hormonal status was determined by central measurements of GH and IGF-I.

Results: Patients (n = 291) had a median GH of 1.43 μg/l (0.65–3.03; IQR), a median IGF-I of 231 μg/l (150–367), and a mean IGF-I z-score of +1.91 (s.d. 2.21). The AcroQoL total score in the whole group was 67.1 (51.1–78.4), with a score of 65.6 (43.8–78.1) for the physical dimension, 67.9 (53.6–80.4) for the psychological dimension, 78.6 (64.3–89.3) for personal relations and 57.1 (39.3–75) for appearance. The median SSS was 3 (–). There was a negative correlation between both questionnaires (r = −0.478; P < 0.001). There was no correlation between AcroQoL score and biochemical markers of disease activity. When subdividing patients into groups of biochemical control according to GH and IGF-I levels, no difference could be established for either SSS or AcroQoL scores.

Conclusions: The AcroQoL results from the AcroBel registry confirm the marked impairment of the patients’ QoL, especially in relation with appearance. A negative correlation between AcroQoL and SSS was confirmed. There was, however, no correlation between AcroQoL and biochemical markers of disease activity.

Free access

AcroBel – the Belgian registry on acromegaly: a survey of the ‘real-life’ outcome in 418 acromegalic subjects

Marie Bex, Roger Abs, Guy T’Sjoen, Jean Mockel, Brigitte Velkeniers, Katja Muermans, and Dominique Maiter

Objectives: To constitute a registry on acromegaly, AcroBel, to evaluate the epidemiology and quality of care of acromegaly in Belgium and Luxembourg.

Design: A nationwide survey from June 2003 till September 2004 aiming to collect data from all patients with acromegaly who had visited the participating endocrine clinics after 1 January 2000.

Methods: Retrospective data collection coupled to a visit within the survey period, allowing sampling of metabolic parameters and centralised determination of GH and IGF-I.

Results: Four hundred and eighteen patients (51% men) were included, of which 96 were new cases, giving a mean incidence of 1.9 cases per million (c.p.m.) per year. The global prevalence was 41 c.p.m. but varied between 21 and 61 among different areas. Twenty-eight deaths were reported at a median age of 68 years in men and 74 years in women. The standardised mortality rate was significantly increased only in irradiated patients (2.70; confidence interval 1.60–4.55). Central measurements were available in 316 (75%) patients. Mean GH was ≤ 2 μg/l in 65% and IGF-I was normal for age in 56%, while both criteria were fulfilled in 49%. Multimodal treatment was more effective than primary medical therapy, since 56.5% were controlled versus 24.3% (P < 0.0001).

Conclusions: AcroBel provides an excellent tool to analyse the prevalence, incidence, treatment modalities and outcome of acromegaly in Belgium. This real-life survey reveals that only half of acromegalic patients received an adequate therapy resulting in cure or disease control when stringent biochemical criteria are used.

Free access

Testosterone, androgen receptor gene CAG repeat length, mood and behaviour in adolescent males

Hans Vermeersch, Guy T'Sjoen, Jean Marc Kaufman, John Vincke, and Mieke Van Houtte

Objectives

Androgen activity has been implicated in a range of traits and behaviours that have well-documented sex differences. However, the results of the studies on the relationship between testosterone and these traits and behaviours are inconsistent. This study has analyzed i) whether CAG repeat length, a presumed modulator of androgen receptor sensitivity, is associated with sex-dimorphic traits and behaviours (aggressive and non-aggressive risk-taking (ART and NART), dominance, depressive symptoms and self-esteem), and ii) whether CAG repeat length interacts with free testosterone (FT) with respect to these traits and behaviours.

Design and methods

Data obtained from a group of adolescent boys (n=301; mean age: 14.4 years) were analyzed using multivariate general linear modelling (SPSS, Chicago, IL, USA 15.0).

Results

We found no direct correlation between CAG repeat length and dependent variables. We found significant interactions between CAG repeat length and testosterone, indicating that FT was more positively related to ART and NART with a shorter repeat length, and that an inverse association of FT with depressive symptoms and a positive association with self-esteem were stronger in boys with a longer CAG repeat length.

Conclusion

Our findings indicate the importance of studying FT and CAG repeat length simultaneously with respect to sex-dimorphic traits, taking into account the possible interactions between the two.

Free access

MANAGEMENT OF ENDOCRINE DISEASE: Optimal feminizing hormone treatment in transgender people

Dorte Glintborg, Guy T’Sjoen, Pernille Ravn, and Marianne Skovsager Andersen

Transgender women are assigned male at birth but identified as women. The incidence of gender dysphoria is estimated to be around 1% of the population. Gender dysphoria may be associated with depression and low quality of life, which in most cases improves during gender-affirming hormonal treatment (GAHT). Feminizing hormonal treatment for transgender women or gender non-binary people typically includes natural estrogen (estradiol). Additional testosterone-blocking treatment is often needed to ensure the suppression of the pituitary-gonadal axis and may include cyproterone acetate, a gonadotropin-releasing hormone agonist (GnRH-a), or spironolactone. The health risks of cyproterone acetate as anti-androgen treatment are debated and randomized protocols with other anti-androgen treatments are requested. Orchiectomy is performed in some transgender women after various duration of GAHT. Currently, natural progesterone is not recommended as part of GAHT due to limited knowledge on the balance between risks and benefits. In the present article, we discuss evidence regarding established and upcoming feminizing treatment for adult transgender women or gender non-binary people seeking feminization. Data on study populations with transgender women are put into a wider context of literature regarding the effects of sex steroid hormones in cisgender study populations. Relevant follow-up and monitoring during feminizing treatment is debated. The review has a special focus on the pharmacotherapy of feminizing hormonal therapy.

Free access

Sexual desire in female-to-male transsexual persons: exploration of the role of testosterone administration

Katrien Wierckx, Els Elaut, Eva Van Caenegem, Fleur Van De Peer, David Dedecker, Ellen Van Houdenhove, and Guy T'Sjoen

Objective

To describe sexual desire in female-to-male transsexual persons post sex reassignment surgery (SRS). The associations between serum androgen levels and sexual desire are examined.

Design

Single center cross-sectional study.

Methods

Forty-five female-to-male transsexual persons post SRS completed a standardized questionnaire assessing sexual desire (Sexual Desire Inventory). In addition, participants were asked questions on sexual desire before starting hormone treatment and having SRS. Serum levels of testosterone, LH and sex hormone-binding globulin were measured on fasting morning serum samples.

Results

In retrospect, 73.9% of the participants reported an increase in sexual desire after hormone treatment and SRS. Solitary sexual desire scores were significantly correlated with frequency of masturbation (r=0.835; P<0.001), whereas frequency of sexual intercourse with a partner was not. No direct associations were found between testosterone and solitary or dyadic sexual desire. However, ANOVA showed an independent effect of LH on solitary sexual desire (P<0.001). Post hoc analysis revealed that female-to-male transsexual persons with elevated levels of LH, indicating suboptimal testosterone therapy, reported significantly lower solitary sexual desire levels (than those with low LH levels; P=0.007). Suppressed LH levels were also associated with having a higher need for sexual activities (P=0.009) and a higher frequency of excessive sexual desire (P=0.007).

Conclusion

Most female-to-male transsexual persons report on a marked increase in sexual desire after testosterone treatment and SRS. No direct associations between levels of testosterone and solitary or dyadic sexual desire were found. However, measures of sexual desire were inversely associated with LH levels.

Free access

Hypoactive sexual desire in transsexual women: prevalence and association with testosterone levels

Els Elaut, Griet De Cuypere, Petra De Sutter, Luk Gijs, Michael Van Trotsenburg, Gunter Heylens, Jean-Marc Kaufman, Robert Rubens, and Guy T'Sjoen

Objective

An unknown proportion of transsexual women (defined as post-operative male-to-female transsexuals on oestrogen replacement) experience hypoactive sexual desire disorder (HSDD). It has been suggested that the absence of ovarian androgen production together with oestrogen treatment-related increase in sex hormone-binding globulin (SHBG) levels could be leading to HSDD, due to low levels of biologically available testosterone. This study wishes to document the HSDD prevalence among transsexual women and the possible association to androgen levels.

Design

Cross-sectional study.

Methods

Transsexual women (n=62) and a control group of ovulating women (n=30) participated in this study. Questionnaires measuring sexual desire (sexual desire inventory) and relationship and sexual satisfaction (Maudsley Marital Questionnaire) were completed. Serum levels of total testosterone, LH and SHBG were measured in blood samples obtained at random in transsexual women and in the early follicular phase in ovulating women.

Results

The transsexual group had lower levels of total and calculated free testosterone (both P<0.001) than the ovulating women. HSDD was reported in 34% of the transsexual and 23% of the ovulating women (P=0.30). Both groups reported similar levels of sexual desire (P=0.97). For transsexual women, no significant correlation was found between sexual desire and total (P=0.64) or free testosterone (P=0.82). In ovulating women, these correlations were significant (P=0.006, resp. P=0.003).

Conclusions

HSDD is reported in one-third of transsexual women. This prevalence is not substantially different from controls, despite markedly lower (free) testosterone levels, which argues against a major role of testosterone in this specific group.

Free access

Active acromegaly is associated with decreased hs-CRP and NT-proBNP serum levels: insights from the Belgian registry of acromegaly

Johan Verhelst, Brigitte Velkeniers, Dominique Maiter, Patrick Haentjens, Guy T'Sjoen, Ernst Rietzschel, Bernard Corvilain, Pascale Abrams, Frank Nobels, Roger Abs, and Marie Bex

Objective

Patients with active acromegaly have an increased prevalence of cardiomyopathy and heart failure but a less than expected risk of coronary artery disease, considering the frequent association of diabetes mellitus and hypertension. We examined whether changes in high-sensitive C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) might contribute to this phenomenon.

Design and methods

Two hundred patients of the Belgian acromegaly registry (AcroBel) were divided in two groups: active disease (IGF1 Z-score >2; n=95) and controlled disease (IGF1 Z-score ≤2; n=105). Serum levels of hs-CRP and NT-proBNP were measured and correlated with BMI, blood pressure, fasting lipids, fasting glucose and insulin, HbA1c, IGF1, interleukin 6 (IL6), adiponectin, and sE-selectin. In a subset of acromegaly patients, hs-CRP, IL6, and NT-proBNP levels were also compared with those/the values of an age-, gender-, and BMI-matched reference group.

Results

Patients with active acromegaly had significantly lower levels of hs-CRP (median (interquartile range), 0.5 mg/l (0.1, 0.9) vs 1.3 mg/l (0.5, 4.1); P<0.001) and NT-proBNP, (47.0 ng/l (26.0, 86.0) vs 71.0 ng/l (43.0, 184.0); P<0.001) compared with patients with controlled acromegaly. Compared with the reference population, hs-CRP was not different in controlled acromegaly but significantly lower in active acromegaly (median, 0.4 mg/l (0.1, 0.8) vs 1.4 mg/l (0.8, 2.9); P<0.001), while NT-proBNP was similar in active acromegaly but significantly higher in controlled acromegaly (66.5 ng/l (40.0, 119.5) vs 50.8 ng/l (26.5, 79.7); P<0.001).

Conclusions

Patients with active acromegaly have significantly lower values of NT-proBNP and hs-CRP compared with patients with controlled disease and even lower values of hs-CRP compared with control subjects.

Free access

Variation in sensitivity and rate of change in body composition: steps toward individualizing transgender care

Daan M van Velzen, Nienke M Nota, Suat Simsek, Elfi B Conemans, Guy T’Sjoen, and Martin den Heijer

Objective

Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change.

Design and methods:

Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage.

Results

A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48–0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01–1.83 per SD increase in LH).

Conclusions:

There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy.

Free access

Is there a need for liver enzyme monitoring in people using gender-affirming hormone therapy?

Theresa A Stangl, Chantal M Wiepjes, Justine Defreyne, Elfi Conemans, Alessandra D Fisher, Thomas Schreiner, Guy T’Sjoen, and Martin den Heijer

Context

Individuals with gender dysphoria can receive gender-affirming hormone therapy. Different guidelines mention a severe risk of liver injury within the first months after the start of treatment with anabolic androgenic steroids, anti-androgens, and oral contraceptives, which is potentially fatal.

Objective

The incidence of liver injury in a transgender population using gender-affirming hormone therapy.

Design

Multicentre prospective study with 1933 transgender individuals, who started with hormone therapy between 2010 and 2020.

Methods

The following parameters were analysed before hormone therapy, after 3 months, and after 12 months of hormone therapy: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). Both male and female reference values were considered. Liver injury was defined as either an elevation of 2× upper limit of normal (ULN) of ALP, 3× ULN of ALT, or 3× ULN of AST.

Results

889 transgender women and 1044 transgender men were included in the analysis. The incidence of liver injury within 12 months after the start of hormone therapy, without attribution to alcohol abuse, medical history, or comedication was 0.1 and 0.0%. in transgender women according to female and male reference intervals respectively, and 0.6 and 0.4% in transgender men (female and male reference intervals).

Conclusion

The incidence of liver injury is found to be very low. We, therefore, conclude that liver enzyme monitoring within the frame of the risk of liver injury due to hormone therapy is not necessary for a transgender population.

Restricted access

Cardiovascular risk in Danish transgender persons: a matched historical cohort study

Dorte Glintborg, Katrine Hass Rubin, Tanja Gram Petersen, Øjvind Lidegaard, Guy T’Sjoen, Malene Hilden, and Marianne Skovsager Andersen

Background

Cardiovascular risk could be increased in transgender persons, but the mechanism is undetermined.

Aim

The aim of this study was to assess the risk of cardiovascular outcomes in Danish transgender persons compared to controls.

Methods

The study design was a historical register-based cohort study in Danish transgenders and age-matched controls. The main outcome measure was cardiovascular diagnosis (any CVD) including medicine prescriptions for CVD during 2000–2018. The transgender cohort (n = 2671) included persons with International Classification of Diseases-10 diagnosis code of ‘gender identity disorder’ (n = 1583) and persons with legal sex change (n = 1088), 1270 were assigned female at birth (AFAB) and 1401 were assigned male at birth (AMAB). Controls (n = 26 710) were matched by age (n = 5 controls of same and n  = 5 controls of other birth sex) of the respective transgender.

Results

The median (interquartile range) age at study inclusion was 22 (18; 29) years for AFAB and 26 (21; 39) years for AMAB. The mean (s.d.) follow-up time was 4.5 (4.2) years for AFAB and 5.7 (4.8) years for AMAB. The hazard ratio (HR) for any CVD was significantly higher in transgenders vs controls of same and other birth sex, with highest adjusted HR in transgenders AFAB vs control men: 2.20 (95% CI: 1.64;2.95), P < 0.001. Gender-affirming hormone treatment (GAHT) explained part of elevated risk of CVD in transgenders AFAB, whereas GAHT did not contribute to the elevated risk of CVD in transgenders AMAB.

Conclusions

The risk of cardiovascular diagnosis was increased in transgenders. The mechanism should be further investigated.