The Hormone and Endocrine Disruptor Laboratory Group

Translational research and innovation in clinical biochemistry of hormones and growth factors involved in sex differentiation and maturation, child growth, and adult reproductive health and human biomonitoring of environmental chemicals potentially affecting endocrine systems.

With focus on development and implementation of diagnostic tools to examine hormone systems involved in sex differentiation and maturation, child growth, and reproductive health, the core of the Hormone and Endocrine Disruptor Laboratory Group is the Hormone Laboratory and the Analytical Chemistry Laboratory at Dept. of Growth and Reproduction, Rigshospitalet.​

Main research and innovation areas include:

Development and implementation of new clinical biochemical tools

We develop and/or implement hormone assays that are relevant for the patients seen in the outpatient clinic at the Dept. of Growth and Reproduction. This includes hormone analyses, which are not commonly available elsewhere (e.g., inhibin B, Insulin-like factor 3 (INSL3), insulin-like binding proteins) but also methods for more common analytes (e.g., luteinizing hormone, estradiol, testosterone). All our assays are, however, optimized with respect to e.g. sensitivity and measurement range to meet the special requirements of our specific patient groups, which also includes infants and prepubertal children. 

Recently we have focused on developing hormone assays based on liquid chromatography - tandem mass spectrometry (LC-MS/MS) methodology, which is superior to immunoassays in specificity and provide the possibility of measuring several analytes in the same methods. We have now established LC-MS/MS methods for analysis of several sex steroid hormones1,2 and INSL33. The latter is currently used to explore INSL3 as a marker of Leydig cell function in both basic and clinical andrology. 

Several of our hormone analyses have initially been implemented and used as research tools, which following clinical validation subsequently have become valuable diagnostic tools in the clinic. Our current routine hormone analysis repertoire is listed in the method list at Rigshospitalet’s Labportal​ (in Danish, search on analyses performed by “Rigshospitalet Blegdamsvej, Afdeling for Vækst og Reproduktion”). Both the Hormone Laboratory and the Analytical Chemistry Laboratory conducting these clinical analyses are accredited according to the ISO 15189 standard for medical laboratories by the Danish Accreditation fund (DANAK).

Characterisation of hormone patterns during normal and pathological sex development and reproductive health

A hallmark of our method implementation is the establishment of in-house sex- and age-related reference ranges for children, adolescents and adults for the hormones and growth factors analyzed in the laboratories2,4-9. This work is done in collaboration with PIs of population-based health studies providing samples for analysis from healthy individuals, including studies conducted at Dept. of Growth and Reproduction10 and at Centre from Clinical Research and Prevention11. Sex- and age-related reference materials are essential for examining the natural history and sex differences of a given hormone over different stages of life and it is an indispensable tool for comparison of hormone changes in abnormal development and disease. 

Our research also includes investigation of the interaction between hormones and how changes in the profiles of associated hormones are related to developmental stages and pathological conditions. We strive to translate this information into improved diagnostic tools as e.g. bivariate reference ranges12,13.

Human biomonitoring and the impact of environmental factors on endocrine systems 

Our Analytical Chemistry Laboratory was established as an analytical facility serving the human studies on endocrine disruption of reproductive health, which have been carried out at Dept. of Growth and Reproduction since mid-1990’ies. Accordingly, since 2004, we have been involved in human biomonitoring (HBM) of several known and suspected non-persistent endocrine disrupting chemicals (e.g., phthalates, parabens, bisphenols, benzophenones and other simple phenols) measured in several human matrices. Our Analytical Chemistry Laboratory served as a European reference laboratory in several completed EU-funded European HBM projects (DEMOCOPHES and HBM4EU). We have provided some of the first data on exposure to these chemicals in the general Danish population14-16 - data which also has been used in the regulatory work of the Danish Environment Protection Agency.

About the Laboratories:

The Hormone Laboratory 

The Hormone Laboratory was established in 1992 with Anna-Maria Andersson as the scientific manager. Since 2019, Trine Holm Johannsen, consultant in clinical biochemistry, has taken over this role and she is also the daily manager of the laboratory, which includes seven biomedical laboratory scientists. The Hormone Laboratory is specialized in hormone analyses by immunoassay methodology and performs annually >60,000 hormone analyses for the clinic and for research projects. 

The Analytical Chemistry laboratory

In 2004 the Analytical Chemistry Laboratory was established as a small research unit with focus on human biomonitoring of phthalate metabolites. Since then, the list of analytes as well as the laboratory facilities (currently houses three online TurboFlow-LC-MS/MS platforms) have expanded under the supervision of chemist Hanne Frederiksen, who joined the team in 2006 as manager of the laboratory. In 2016, biochemist Jakob Albrethsen joined the group bringing experience in LC-MS of peptide hormones to the team. The Analytical Chemistry Laboratory staff also includes two biomedical laboratory scientists, and annually about 14,000 analyses are performed, including from 3 to 36 analytes for the clinic and for research projects. 

Current national and international collaborations

European Partnership for the Assessment of Risks from Chemicals – PARC 2022 - 2027

The Capital Region of Denmark (Region Hovedstaden) participate in PARC with Dept. of Growth and Reproduction as one of two representatives. In this project members of the Hormone and Endocrine Disruptor Laboratory Group we contribute with our expertise as reference laboratory from previous EU projects and our experience in human biomonitoring and studies on exposure-health associations. 

The European Reference Network on Rare Endocrine Conditions (Endo-ERN) 

Endo-ERN is a virtual network involving reference centers across Europe with the aim to improve access to high-quality healthcare for patients with hormonal disorders. Dept. of Growth and Reproduction is one of these reference centers. The Endo-ERN network is a channel for dissemination of innovation carried out within the Hormone and Endocrine Disruptor Laboratory group. Endo-ERN is based on the EU 3rd Health Program

Danish National Centre on Endocrine Disruptors (CeHoS)

Group leader Anna-Maria Andersson has been leader of the Danish National Centre on Endocrine Disrupters since it started in 2008. She and group member Hanne Frederiksen have, together with other colleagues at Dept. of Growth and Reproduction, carried out several project under CeHoS including HBM projectse.g.14-16. The Centre, which is a partnership between Rigshospitalet, the Technical University of Denmark and University of Southern Denmark, reports directly to the Danish Environment Protection Agency.

Odense Child Cohort

We have a longstanding collaboration with the PI of Odense Child Cohort17, Prof. Tina Kold Jensen. We have on several occasions analysed hormones and endocrine disrupting chemicals in samples collected in the study18-20.   ​

Current members of the group:

  • Anna-Maria Andersson, MSc, Ph.D, Research director and Group leader
  • Hanne Frederiksen, MSc, Ph.D, senior scientist and chemist, Leader of the Analytical Chemistry Laboratory
  • Trine Holm Johansen, M.D, Ph.D. Consultant in Clinical Biochemistry, Leader of the Hormone Laboratory
  • Jakob Christian Albrethsen, MSc, Ph.D, senior scientist and biochemist 

Affiliated biomedical laboratory scientists:

The Hormone Laboratory

  • Asma Khan
  • Emilie Holm Rasmussen
  • Irina Safonenko
  • Jessica Winther
  • Maiken Probst
  • Marianne Seilund
  • Karina Skou

The Analytical Chemistry Laboratory

  • Ole Nielsen
  • Stine Ehlern Andersen 

1Søeborg T, Frederiksen H, Johannsen TH, Andersson AM, Juul A. Isotope-dilution TurboFlow-LC-MS/MS method for simultaneous quantification of ten steroid metabolites in serum. Clin Chim Acta. 2017, 468:180-186. ​

2Frederiksen H, Johannsen TH, Andersen SE, Albrethsen J, Landersoe SK, Petersen JH, Andersen AN, Vestergaard ET, Schorring ME, Linneberg A, Main KM, Andersson AM, Juul A. Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS. J Clin Endocrinol Metab. 2020, 105:754–68.

3Albrethsen J, Frederiksen H, Andersson AM, Anand-Ivell R, Nordkap L, Bang AK, Jørgensen N, Juul A. Development and validation of a mass spectrometry-based assay for quantification of insulin-like factor 3 in human serum. Clin Chem Lab Med. 2018, 56:1913-1920

4Johannsen TH, Main KM, Ljubicic ML, Jensen TK, Andersen HR, Andersen MS, Petersen JH, Andersson AM, Juul A. Sex Differences in Reproductive Hormones During Mini-Puberty in Infants with Normal and Disordered Sex Development. J Clin Endocrinol Metab. 2018;103:3028-3037. 

5Johannsen TH, Andersson AM, Ahmed SF, de Rijke YB, Greaves RF, Hartmann MF, Hiort O, Holterhus PM, Krone NP, Kulle A, Ljubicic ML, Mastorakos G, McNeilly J, Pereira AM, Saba A, Wudy SA, Main KM, Juul A. Peptide hormone analysis in diagnosis and treatment of Differences of Sex Development: joint position paper of EU COST Action 'DSDnet' and European Reference Network on Rare Endocrine Conditions. Eur J Endocrinol. 2020, 182:P1-P15.

6Mouritsen A, Søeborg T, Hagen CP, Mieritz MG, Johannsen TH, Frederiksen H, Andersson AM, Juul A. Longitudinal changes in serum concentrations of adrenal androgen metabolites and their ratios by LC-MS/MS in healthy boys and girls. Clin Chim Acta. 2015, 450:370-5.

7Ljubicic ML, Jespersen K, Aksglaede L, Hagen CP, Petersen JH, Andersen HR,Linneberg A, Main KM, Andersson AM, Johannsen TH, Juul A. The LH/FSH ratio is not a sex-dimorphic marker after infancy: data from 6417 healthy individuals and 125 patients with Differences of Sex development. Hum Reprod. 2020,35:2323-2335.

8Søeborg T, Frederiksen H, Mouritsen A, Johannsen TH, Main KM, Jørgensen N, Petersen JH, Andersson AM, Juul A. Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults. Clin Chim Acta. 2014, 437:6-13.

9Albrethsen J, Ljubicic ML, Juul A. Longitudinal Increases in Serum Insulin-like Factor 3 and Testosterone Determined by LC-MS/MS in Pubertal Danish Boys. JClin Endocrinol Metab. 2020 105:dgaa496.

 10E.g. The Copenhagen puberty study and the Copenhagen mini-puberty  study and the Copenhagen Puberty Studies led by Prof. Anders Juul, The Male reproductive health study led by Senior Consultant Niels Jørgensen and the Mother-Child cohort lead by Prof. Katharina Main.  For details of the population studies, please see edmarc.net/population-studies.html

 11E.g. MONICA studies, Health 2006 and 2008; collaboration with Prof. Allan Linneberg.

 12Andersson AM, Petersen JH, Jørgensen N, Jensen TK, Skakkebæk NE. Serum inhibin B and follicle-stimulating hormone levels as tools in the evaluation of infertile men: significance of adequate reference values from proven fertile men. J Clin Endocrinol Metab. 2004 Jun;89(6):2873-9.

13Aksglaede L, Andersson AM, Jørgensen N, Jensen TK, Carlsen E, McLachlan RI, Skakkebaek NE, Petersen JH, Juul A. Primary testicular failure in Klinefelter's syndrome: the use of bivariate luteinizing hormone-testosterone reference charts. Clin Endocrinol (Oxf). 2007 Feb;66(2):276-81. 

 14Frederiksen H, Jensen TK, Jørgensen N, Kyhl HB, Husby S, Skakkebæk NE, Main KM, Juul A, Andersson AM. Human urinary excretion of non-persistent environmental chemicals: an overview of Danish data collected between 2006 and 2012.Reproduction. 2014 Mar 4;147(4):555-65

15Frederiksen H, Upners EN, Ljubicic ML, Fischer MB, Busch AS, Hagen CP, Juul A, Andersson AM. Exposure to 15 phthalates and two substitutes (DEHTP and DINCH) assessed in trios of infants and their parents as well as longitudinally in infants exclusively breastfed and after the introduction of a mixed diet. Environ Int. 2022 Mar;161:107107.

16Frederiksen H, Ljubicic ML, Upners EN, Fischer MB, Busch AS, Hagen CP, Juul A, Andersson AM. Benzophenones, bisphenols and other polychlorinated/phenolic substances in Danish infants and their parents - including longitudinal assessments before and after introduction to mixed diet. Environ Int. 2022 Nov;169:107532.

17odenseboernekohorte.dk - website in Danish

18Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM. Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010-2012). Environ Health Perspect. 2016, 124:1107-13.

19Jensen TK, Mustieles V, Bleses D, Frederiksen H, Trecca F, Schoeters G, Andersen HR, Grandjean P, Kyhl HB, Juul A, Bilenberg N, Andersson AM. Prenatal bisphenol A exposure is associated with language development but not with ADHD-related behavior in toddlers from the Odense Child Cohort. Environ Res. 2019, 170:398-405.

20Højsager FD, Kyhl HB, Frederiksen H, Juul A, Andersson AM, Andersen MS, Grøntved A, Jensen TK. Prenatal Exposure to Butyl Paraben is Associated with Fat Percentage in 7-Year-Old Boys. J Clin Endocrinol Metab. 2021, 106(7):e2633-e2638. ​







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