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Article ; Online: Anabolic Androgenic Steroids Induce Reversible Left Ventricular Hypertrophy and Cardiac Dysfunction. Echocardiography Results of the HAARLEM Study

Diederik L. Smit / A. J. Voogel / Martin den Heijer / Willem de Ronde

Frontiers in Reproductive Health, Vol

2021 Volume 3

Abstract: Background: The use of anabolic androgenic steroids (AAS) is not uncommon among strength athletes. Several cross-sectional studies have linked AAS use to heart disease, but a causal role for AAS is not certain and it is unknown whether cardiac changes ... ...

Abstract	Background: The use of anabolic androgenic steroids (AAS) is not uncommon among strength athletes. Several cross-sectional studies have linked AAS use to heart disease, but a causal role for AAS is not certain and it is unknown whether cardiac changes are reversible.Methods: Men of at least 18 years old intending to start an AAS cycle on short notice were included for comprehensive 3D echocardiographic examination before (T0), at the end of the cycle (T1), and 1 year after inclusion (T2) after a recovery period. Details of the AAS cycle performed and the use of other performance and image-enhancing drugs (PIEDs) as well as illicit drug use were recorded. Trend analysis and multivariable regression analysis were performed with mixed effects linear models.Results: Thirty-one subjects were included. Between start (T0) and end of the cycle (T1), after a median AAS cycle duration of 16 weeks, 3D left ventricular ejection fraction declined with 4.9% (CI −7.2 to −2.5, P < 0.001), E/A-ratio declined with−0.45 (CI −0.69 to −0.21, P < 0.001), and 3D left atrial volume increased with 9.2 ml (CI 2.9–15.4, P = 0.004). Left ventricular mass increased with 28.3 g (CI 14.2–42.4, P < 0.001) and was positively correlated with AAS average weekly dose. After a median recovery time of 8 months (T2), all parameters returned to baseline.Conclusion: AAS induce left ventricular hypertrophy and impaired systolic and diastolic function in amateur strength athletes. The structural cardiac changes are positively associated with AAS dose and complete recovery occurred after AAS were discontinued.
Keywords	anabolic steroids ; performance and image-enhancing drugs ; strength athletes ; bodybuilding ; three-dimensional echocardiography ; Reproduction ; QH471-489 ; Medicine (General) ; R5-920
Subject code	796
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The effect of transdermal gender-affirming hormone therapy on markers of inflammation and hemostasis

Moya H. Schutte / Robert Kleemann / Nienke M. Nota / Chantal M. Wiepjes / Jessica M. Snabel / Guy T’Sjoen / Abel Thijs / Martin den Heijer

PLoS ONE, Vol 17, Iss

2022 Volume 3

Abstract: Background Cardiovascular risk is increased in transgender persons using gender-affirming hormone therapy. To gain insight into the mechanism by which sex hormones affect cardiovascular risk in transgender persons, we investigated the effect of hormone ... ...

Abstract	Background Cardiovascular risk is increased in transgender persons using gender-affirming hormone therapy. To gain insight into the mechanism by which sex hormones affect cardiovascular risk in transgender persons, we investigated the effect of hormone therapy on markers of inflammation and hemostasis. Methods In this exploratory study, 48 trans women using estradiol patches plus cyproterone acetate (CPA) and 47 trans men using testosterone gel were included. They were between 18 and 50 years old and did not have a history of cardiovascular events. Measurements were performed before and after 3 and 12 months of hormone therapy. Results After 12 months, in trans women, systemic and endothelial inflammatory markers decreased (hs-CRP -66%, (95% CI -76; -53), VCAM-1–12%, (95% CI -16; -8)), while platelet activation markers increased (PF-4 +17%, (95% CI 4; 32), β-thromboglobulin +13%, (95% CI 2; 24)). The coagulation marker fibrinogen increased transiently, after 3 months (+15%, (95% CI 1; 32)). In trans men, hs-CRP increased (+71%, (95% CI 19; 145)); platelet activation and coagulation markers were not altered. In both trans women and trans men, leptin and adiponectin changed towards reference values of the experienced gender. Conclusions Platelet activation and coagulation marker concentrations increased in trans women using transdermal estradiol plus CPA, but not in trans men using testosterone. Also, concentrations of inflammatory markers decreased in trans women, while hs-CRP increased in trans men. Our results indicate that hormone therapy may affect hemostasis in transgender persons, which could be an underlying mechanism explaining the increased cardiovascular risk in this population.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The ENIGI (European Network for the Investigation of Gender Incongruence) Study

Carlotta Cocchetti / Alessia Romani / Sarah Collet / Yona Greenman / Thomas Schreiner / Chantal Wiepjes / Martin den Heijer / Guy T’Sjoen / Alessandra Daphne Fisher

Journal of Clinical Medicine, Vol 11, Iss 1784, p

Overview of Acquired Endocrine Knowledge and Future Perspectives

2022 Volume 1784

Abstract: Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgender people is limited. For this reason, in 2010 the European Network for the Investigation of Gender Incongruence (ENIGI) study was born. The aim of this ... ...

Abstract	Literature on the efficacy and safety of gender-affirming hormonal treatment (GAHT) in transgender people is limited. For this reason, in 2010 the European Network for the Investigation of Gender Incongruence (ENIGI) study was born. The aim of this review is to summarize evidence emerging from this prospective multicentric study and to identify future perspectives. GAHT was effective in inducing desired body changes in both trans AMAB and AFAB people (assigned male and female at birth, respectively). Evidence from the ENIGI study confirmed the overall safety of GAHT in the short/mid-term. In trans AMAB people, an increase in prolactin levels was demonstrated, whereas the most common side effects in trans AFAB people were acne development, erythrocytosis, and unfavorable changes in lipid profile. The main future perspectives should include the evaluation of the efficacy and safety of non-standardized hormonal treatment in non-binary trans people. Furthermore, long-term safety data on mortality rates, oncological risk, and cardiovascular, cerebrovascular and thromboembolic events are lacking. With this aim, we decided to extend the observation of the ENIGI study to 10 years in order to study all these aspects in depth and to answer these questions.
Keywords	gender incongruence ; gender dysphoria ; transgender ; ENIGI ; prospective cohort study ; gender-affirming hormonal treatment ; Medicine ; R
Subject code	910
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The effect of transdermal gender-affirming hormone therapy on markers of inflammation and hemostasis.

Moya H Schutte / Robert Kleemann / Nienke M Nota / Chantal M Wiepjes / Jessica M Snabel / Guy T'Sjoen / Abel Thijs / Martin den Heijer

PLoS ONE, Vol 17, Iss 3, p e

2022 Volume 0261312

Abstract	Background Cardiovascular risk is increased in transgender persons using gender-affirming hormone therapy. To gain insight into the mechanism by which sex hormones affect cardiovascular risk in transgender persons, we investigated the effect of hormone therapy on markers of inflammation and hemostasis. Methods In this exploratory study, 48 trans women using estradiol patches plus cyproterone acetate (CPA) and 47 trans men using testosterone gel were included. They were between 18 and 50 years old and did not have a history of cardiovascular events. Measurements were performed before and after 3 and 12 months of hormone therapy. Results After 12 months, in trans women, systemic and endothelial inflammatory markers decreased (hs-CRP -66%, (95% CI -76; -53), VCAM-1-12%, (95% CI -16; -8)), while platelet activation markers increased (PF-4 +17%, (95% CI 4; 32), β-thromboglobulin +13%, (95% CI 2; 24)). The coagulation marker fibrinogen increased transiently, after 3 months (+15%, (95% CI 1; 32)). In trans men, hs-CRP increased (+71%, (95% CI 19; 145)); platelet activation and coagulation markers were not altered. In both trans women and trans men, leptin and adiponectin changed towards reference values of the experienced gender. Conclusions Platelet activation and coagulation marker concentrations increased in trans women using transdermal estradiol plus CPA, but not in trans men using testosterone. Also, concentrations of inflammatory markers decreased in trans women, while hs-CRP increased in trans men. Our results indicate that hormone therapy may affect hemostasis in transgender persons, which could be an underlying mechanism explaining the increased cardiovascular risk in this population.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Using a BonE BiOPsy (BeBoP) to determine the causative agent in persons with diabetes and foot osteomyelitis

Meryl Cinzía Tila Tamara Gramberg / Rimke Sabine Lagrand / Louise Willy Elizabeth Sabelis / Martin den Heijer / Vincent de Groot / Max Nieuwdorp / Willemijn Kortmann / Elske Sieswerda / Edgar Josephus Gerardus Peters

Trials, Vol 22, Iss 1, Pp 1-

study protocol for a multicentre, randomised controlled trial

2021 Volume 10

Abstract: Abstract Background Diabetic foot osteomyelitis (DFO) poses a major disease burden. It can generally be treated with long-term antibacterial therapy. International guidelines recommend to base antibacterial therapy choices on percutaneous bone biopsy ... ...

Abstract	Abstract Background Diabetic foot osteomyelitis (DFO) poses a major disease burden. It can generally be treated with long-term antibacterial therapy. International guidelines recommend to base antibacterial therapy choices on percutaneous bone biopsy culture, while in practice, therapy is frequently based on (less invasive) ulcer bed cultures. It is currently unknown if treatment outcomes of DFO differ depending on the chosen diagnostic strategy. Methods The BeBoP trial is a multicentre; randomised controlled; physician-, researcher- and subject-blinded; clinical trial comparing two diagnostic strategies in persons with DFO. Culture-directed antibacterial therapy will be based on either percutaneous bone biopsy culture results (intervention group) or ulcer bed biopsy culture results (comparison group). We will enrol 80 subjects with diabetes mellitus (≥ 18 years) and DFO, and we will use block randomisation stratified per centre to randomise them in a 1:1 allocation. The primary outcome is remission of DFO 12 months after enrolment. The secondary outcomes are the time to remission, signs of inflammation or ulceration at the primary location of infection at 6 and 12 months, microbiological and molecular profiles of culture outcomes, surgical interventions including amputation, total antibacterial therapy duration, infection-free survival days, adverse events, quality of life and survival. We will compare the outcomes by intention-to-treat and per-protocol analysis. Discussion We aim to compare clinical remission in persons with DFO treated with antibacterial therapy based on either percutaneous bone biopsy culture results or ulcer bed biopsy culture results. Trial registration Netherlands Trial Register NL 7582 . Registered on 05 March 2019
Keywords	Osteomyelitis in diabetic foot ; Bone biopsy ; Antibacterial therapy ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Positive and Negative Affect Changes during Gender-Affirming Hormonal Treatment

Imke Matthys / Justine Defreyne / Els Elaut / Alessandra Daphne Fisher / Baudewijntje P. C. Kreukels / Annemieke Staphorsius / Martin Den Heijer / Guy T’Sjoen

Journal of Clinical Medicine, Vol 10, Iss 2, p

Results from the European Network for the Investigation of Gender Incongruence (ENIGI)

2021 Volume 296

Abstract: Improving transgender people’s quality of life (QoL) is the most important goal of gender-affirming care. Prospective changes in affect can influence QoL. We aim to assess the impact of initiating gender-affirming hormonal treatment (HT) on affect. In ... ...

Abstract	Improving transgender people’s quality of life (QoL) is the most important goal of gender-affirming care. Prospective changes in affect can influence QoL. We aim to assess the impact of initiating gender-affirming hormonal treatment (HT) on affect. In the European Network for the Investigation of Gender Incongruence (ENIGI) study, we prospectively collected data of 873 participants (451 transwomen (TW) and 422 transmen (TM)). At baseline, psychological questionnaires including the Positive and Negative Affect Schedule (PANAS) were administered. The PANAS, levels of sex steroids and physical changes were registered at each follow-up visit during a 3-year follow-up period, starting at the initiation of hormonal therapy. Data were analyzed cross-sectionally and prospectively. Over the first three months, we observed a decline in positive affect (PA) in both TM and TW. Thereafter, PA reached a steady state in TW, whereas in TM there was also a second decline at 18 months. In both TM and TW there was no persisting difference comparing baseline to the 36-months results. Concerning negative affect (NA), we observed a decline during the first year in TM, which sustained during the second year and was not different anymore at 36 months compared to baseline. In TW though, we did not find any change of NA during the entire follow-up. Even if some of these results show significant differences, they should be considered with caution, since there was no control group and the absolute differences are small. No association between affect and the level of sex steroids was observed. Baseline QoL and psychological burden are related to affect independently from gender but are not necessarily good predictors of the evolution of one’s affect during the gender-affirming process. Further research is necessary to investigate these preliminary results.
Keywords	affect ; quality of life ; gender-affirming hormonal treatment ; PANAS questionnaire ; estrogens ; testosterone ; Medicine ; R
Subject code	150
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy.

Ruifang Li-Gao / David A Hughes / Saskia le Cessie / Renée de Mutsert / Martin den Heijer / Frits R Rosendaal / Ko Willems van Dijk / Nicholas J Timpson / Dennis O Mook-Kanamori

PLoS ONE, Vol 14, Iss 6, p e

2019 Volume 0218549

Abstract: Introduction It is crucial to understand the factors that introduce variability before applying metabolomics to clinical and biomarker research. Objectives We quantified technical and biological variability of both fasting and postprandial metabolite ... ...

Abstract	Introduction It is crucial to understand the factors that introduce variability before applying metabolomics to clinical and biomarker research. Objectives We quantified technical and biological variability of both fasting and postprandial metabolite concentrations measured using 1H NMR spectroscopy in plasma samples. Methods In the Netherlands Epidemiology of Obesity study (n = 6,671), 148 metabolite concentrations (101 metabolites belonging to lipoprotein subclasses) were measured under fasting and postprandial states (150 minutes after a mixed liquid meal). Technical variability was evaluated among 265 fasting and 851 postprandial samples, with the identical blood plasma sample being measured twice by the same laboratory protocol. Biological reproducibility was assessed by measuring 165 individuals twice across time for evaluation of short- (<6 months) and long-term (>3 years) biological variability. Intra-class coefficients (ICCs) were used to assess variability. The ICCs of the fasting metabolites were compared with the postprandial metabolites using two-sided paired Wilcoxon test separately for short- and long-term measurements. Results Both fasting and postprandial metabolite concentrations showed high technical reproducibility using 1H NMR spectroscopy (median ICC = 0.99). Postprandial metabolite concentrations revealed slightly higher ICC scores than fasting ones in short-term repeat measures (median ICC in postprandial and fasting metabolite concentrations 0.72 versus 0.67, Wilcoxon p-value = 8.0×10-14). Variability did not increase further in a long-term repeat measure, with median ICC in postprandial of 0.64 and in fasting metabolite concentrations 0.66. Conclusion Technical reproducibility is excellent. Biological reproducibility of postprandial metabolite concentrations showed a less or equal variability than fasting metabolite concentrations over time.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effect of antiretroviral therapy on bone turnover and bone mineral density in men with primary HIV-1 infection.

Mariska C Vlot / Marlous L Grijsen / Jan M Prins / Renate T de Jongh / Robert de Jonge / Martin den Heijer / Annemieke C Heijboer

PLoS ONE, Vol 13, Iss 3, p e

2018 Volume 0193679

Abstract: Previous studies indicate that human immunodeficiency virus (HIV)-infection and combination antiretroviral therapy (cART) can affect bone turnover. Furthermore, HIV-infected patients have lower bone mineral density (BMD) compared to a healthy reference ... ...

Abstract	Previous studies indicate that human immunodeficiency virus (HIV)-infection and combination antiretroviral therapy (cART) can affect bone turnover. Furthermore, HIV-infected patients have lower bone mineral density (BMD) compared to a healthy reference population.To evaluate the longitudinal effect of HIV-infection and cART on bone turnover markers (BTMs) and BMD in men with primary HIV-infection (PHI).Thirty-five PHI-men were divided into two groups, those that received cART for the first time (n = 26) versus no-cART (n = 9). Dual-energy X-ray absorptiometry (DXA) was performed on femoral neck (FN), total hip (TH) and lumbar spine (LS) and BTMs (P1NP, alkaline phosphatase, osteocalcin, ICTP and CTX) were measured at baseline and follow-up.At baseline, the median CD4+ T-cell count was 455 cells/mm3 (IQR 320-620) and plasma viral load 5.4 log10 copies/mL (IQR 4.7-6.0) in the cART treated group, compared to 630 (IQR 590-910) and 4.8 (IQR 4.2-5.1) in the untreated group. The median follow-up time was 60.7 weeks (IQR 24.7-96.0). All BTMs, except ICTP, showed a significant increase during cART versus no changes of BTMs in the untreated group. FN and TH BMD showed a significant decrease in both groups. LS BMD did not change in both groups.Bone turnover increased in PHI-men treated with cART which was accompanied by a decrease in FN and TH BMD. No increase of bone turnover was seen in untreated PHI-men. Our study suggests that cART results in increased bone turnover and decreased BMD of the hip in PHI-men.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Poor sleep quality and later sleep timing are risk factors for osteopenia and sarcopenia in middle-aged men and women

Eliane A Lucassen / Renée de Mutsert / Saskia le Cessie / Natasha M Appelman-Dijkstra / Frits R Rosendaal / Diana van Heemst / Martin den Heijer / Nienke R Biermasz / NEO study group

PLoS ONE, Vol 12, Iss 5, p e

The NEO study.

2017 Volume 0176685

Abstract: Sleep deprivation has detrimental metabolic consequences. Osteopenia and sarcopenia usually occur together and increase risk of fractures and disease. Results from studies linking sleep parameters to osteopenia or sarcopenia are scarce and inconsistent ... ...

Abstract	Sleep deprivation has detrimental metabolic consequences. Osteopenia and sarcopenia usually occur together and increase risk of fractures and disease. Results from studies linking sleep parameters to osteopenia or sarcopenia are scarce and inconsistent.To examine the associations of sleep parameters with osteopenia and sarcopenia, considering the influence of sex and menopause.Cross-sectional analysis of 915 participants (45-65 years, 56% women, BMI 26 (range: 18-56) kg/m2) in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. Sleep duration, quality, and timing were assessed with the Pittsburgh Sleep Quality Index (PSQI); bone mineral density and relative appendicular muscle mass were measured by DXA scans. Linear and logistic regressions were performed to associate sleep parameters to bone mineral density, relative appendicular muscle mass, osteopenia (t-score between -1 and -2.5) and sarcopenia (1 SD below average muscle mass).After adjustment for confounding factors, one unit increase in PSQI score (OR and 95% CI, 1.09, 1.03-1.14), declined self-rated sleep quality (1.76, 1.03-3.01), sleep latency (1.18, 1.06-1.31), and a one hour later sleep timing (1.51, 1.08-2.11), but not sleep duration (1.05, 0.90-1.23), were associated with osteopenia. PSQI score (1.10, 1.02-1.19) was also associated with sarcopenia; OR's of sleep latency and later mid-sleep time with sarcopenia were 1.14 (0.99-1.31) and 1.54 (0.91-2.61), respectively. Associations were somewhat stronger in women and varied per menopausal status.These results suggest that decreased sleep quality and a later sleep timing are risk factors for osteopenia and sarcopenia in middle aged individuals.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Poor sleep quality and later sleep timing are risk factors for osteopenia and sarcopenia in middle-aged men and women

Eliane A Lucassen / Renée de Mutsert / Saskia le Cessie / Natasha M Appelman-Dijkstra / Frits R Rosendaal / Diana van Heemst / Martin den Heijer / Nienke R Biermasz

PLoS ONE, Vol 12, Iss 5, p e

The NEO study.

2017 Volume 0176685

Abstract	Sleep deprivation has detrimental metabolic consequences. Osteopenia and sarcopenia usually occur together and increase risk of fractures and disease. Results from studies linking sleep parameters to osteopenia or sarcopenia are scarce and inconsistent.To examine the associations of sleep parameters with osteopenia and sarcopenia, considering the influence of sex and menopause.Cross-sectional analysis of 915 participants (45-65 years, 56% women, BMI 26 (range: 18-56) kg/m2) in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. Sleep duration, quality, and timing were assessed with the Pittsburgh Sleep Quality Index (PSQI); bone mineral density and relative appendicular muscle mass were measured by DXA scans. Linear and logistic regressions were performed to associate sleep parameters to bone mineral density, relative appendicular muscle mass, osteopenia (t-score between -1 and -2.5) and sarcopenia (1 SD below average muscle mass).After adjustment for confounding factors, one unit increase in PSQI score (OR and 95% CI, 1.09, 1.03-1.14), declined self-rated sleep quality (1.76, 1.03-3.01), sleep latency (1.18, 1.06-1.31), and a one hour later sleep timing (1.51, 1.08-2.11), but not sleep duration (1.05, 0.90-1.23), were associated with osteopenia. PSQI score (1.10, 1.02-1.19) was also associated with sarcopenia; OR's of sleep latency and later mid-sleep time with sarcopenia were 1.14 (0.99-1.31) and 1.54 (0.91-2.61), respectively. Associations were somewhat stronger in women and varied per menopausal status.These results suggest that decreased sleep quality and a later sleep timing are risk factors for osteopenia and sarcopenia in middle aged individuals.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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