Stefan Arver group - Andrology/sexual medicine
We are a multidisciplinary group formed from a number of clinical and research based needs. The following areas of competence are currently represented in the group: endocrinology, psychiatry, behavioural science, laboratory medicine, preclinical cell and molecular biology as well as nursing.
Information film about the research project Priotab. Credit: Studio Annalog
We are working on the following major projects:
A longitudinal study of individuals with gender dysphoria who undergo gender confirmation surgery. They were born and grew up with a hormonal development and influence in accordance with the birth sex and, as a part of the gender confirmation surgery, change their gender hormone system as adults. After month after basal measurements they are examined with GnRH antagonists and thereafter after 3, 6 and 12 months with cross-sex hormone therapy. The study aims to examine how a change of the hormonal environment affects vessels, cardiac function, muscle mass, muscle strength and morphological and functional studies of muscle cells from biopsy, epigenetic studies of leukocyte fractions and skin biopsies, body composition (full-body MRI), ex vivo studies of subcutant adipocytes as well as morphological and functional MRI by defined regions of the brain. The study is a collaboration between us, the Division of clinical physiology, the Cardiology unit, the Neurology unit MRI section x-ray, CMM and Juha Kere's group. We plan to include a total of 40 patients, seven have been included in total since the start in July of 2015.
Emergency treatment of persons at imminent risk of committing acts of sexual abuse. This is a double blind placebo controlled study of the effect of acute deregulation of the hypothalamic–pituitary–gonadal axis with GnRH antagonists. The study includes evaluation of the response with validated questionnaires, psychometric tests and fMRI. The purpose is partly to evaluate the effect of the treatment's impact on central regulatory mechanisms for behaviour control and collectively identify biomarkers for trigger patterns for paedophilia and the risk of committing acts of abuse. There is also an ethical part of the project in which, in the ethical assessment, there is nothing defined in terms of consideration for a third party. The project PI (Principal Investigator) is Christoffer Rahm, post doc, and includes fMRI expertise Benny Liberg, fellow psychologists, endocrinologists and an ethics researcher (Manne Sjöstrand).
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Important for patients with dysglycemia and cardiovascular disease. Doctoral programme, Unit of Cardiology, Department of Medicine, Solna, for Anne Wang, PhD, with Linda Mellbin (principal supervisor), Stefan Arver and Lars Rydén (co-supervisors). CASM contributes laboratory expertise, genetic analyses (androgen receptor, polymorphism) and is responsible for steroid hormone analysis.
Genetic background of reduced sperm motility
Postdoc programme of Rebecka Holmberg. Impaired sperm motility is a common cause of reduced fertility. Some of the mutations that can cause it are already known but we now have the possibility, in a larger population, to identify hitherto unknown genetic variants, which could be related to more mitochondrial function than to structural changes. Together with Dr Anna Lindstrand, Clinical Genetics, we have set up a programme for the genetic analysis of a large quantity of genes related to ciliary structure and sperm function. By systematically collecting DNA from well characterised phenotypes (men with reduced fertility), this project can identify underlying genetic changes to explain the deviations in sperm function.
In collaboration with Dr Kjell Hultenby, Clinical Pathology, we have the opportunity to study the correlation between impaired motility, structural changes and genetic variants. Using the same material we also have men with reduced quantitative and qualitative sperm formation. A natural extension of the project would be to find the genetic causes of this.
Development of sperm and semen analysis
Evaluation of methods for the development of laboratory andrology for the purpose of improving the diagnostics and efficacy of assisted reproductive techniques.
Despite in-vitro fertilization having revolutionised the clinical treatment of infertility, 40-50% of treated couples today never have a biological child, and the reason for this is unknown. It is therefore imperative that we not only develop laboratory-technical methods but also build up a knowledge fundament as the basis for diagnostics and treatment.
a. Studies about the preparation and selection of sperm and how mobility and related characteristics of sperm are affected by different factors in such processes. (Emma Holmes, main supervisor Ulrik Kvist).
b. Studies of how structure and stability in the DNA of sperm are influenced by different factors and the effects on fertilization, pregnancy and foetal development (Emelie Ekwurtzel, main supervisor Ulrik Kvist)
c. Studies of flow cytometric methods for measuring deviations in the sperm DNA, identification of key factors that affect the measurement results to ascertain clinical relevance of the measurement method (Petr Houska).
Clinically relevant changes in muscle function
Clinically relevant changes in muscle function among men undergoing treatment for rectal cancer
This is a continuation of the doctoral programme which was conclude earlier this year with Christina Buchlis' public defence. A new PhD, John Tapper, shall investigate regional differences in the sensitivity of various muscle groups to changes in androgen levels. The rectal cancer group is a patient group, but we will also have access to data from men who have undergone controlled dose response studies of androgens and an intervention study of “frail elderly men with sarcopenia”. The latter is a collaboration with S Bhasin's group at Brigham and Women's Hospital, Harvard Medical School, Boston.
Investigation of testosterone therapy for male hyopgonadism and it’s effect on metabolism
Project leader: John Flanagan
In recent years, a growing body of evidence has established that hypogonadism/low testosterone in men is an independent risk factor for the development of metabolic syndrome, type 2 diabetes and cardiovascular disease. The therapeutic recommended approach is testosterone replacement therapy (TRT), however, clinical studies have been conflicting with some demonstrating beneficial effects of therapy on glycemic control, insulin resistance, serum lipid profile, body composition, and central adiposity, while others showing little to no benefit. Yet, it is estimated that 4-5 million men in the U.S. suffer from hypogonadism with only 5% receiving replacement therapy according to the American Endocrine Society.
Moreover, the projected annual sales of testosterone replacement products is over 1.5 billion dollars in the U.S. alone. Based on our own clinical studies and experience at the Center of Andrology and Sexual Medicine, we have observed only about a third of hypogonadal males with type-2 diabetes and metabolic syndrome respond and benefit to TRT (refer to as ‘high’ anabolic responders). Assessment of TRT in hypogonadal men with comorbidities lack relevant endpoints and simple surrogate predictors for such endpoints. The current repertoire of diagnostic predictors for TRT therapy is limited. Hence, there is a great need for identifying predictors for ‘high’ responders in order to improve the selection criteria for personalized TRT to improved therapy. The prevailing questions for this project are 1) can ‘high’ anabolic responders be define in TRT androgen-deficient with men comorbidities by clinical predictors and potential mediators of testosterone’s anabolic/metabolic effects and used to improve selection criteria for tailored TRT and 2) are candidate mediators of testosterone actions required for proper anabolic/metabolic effects in hypogonadal men and can the lack of response to TRT define the ‘non-responsive’ hypogonadal man to therapy.
The aims of the project are: 1) to characterize TRT in ‘high-responders’ and ‘non-responders’ hypogonadal men with comorbidities; 2) to evaluate the efficacy of dose response relationship between testosterone treatment and predictors of testosterone’s anabolic effects in clinical experimental models of male hypogonadism; 3) explore the possibility that certain novel candidate mediators of testosterone actions are required for proper anabolic/metabolic effects in hypogonadal men. The main objectives for this project utilizes concluded clinical trail data and samples from TRT hypogonadal men with diabetes and metabolic syndrome studies, recruitment of new patients for TRT for further studies, examine TRT in unique clinical experimental human and animal hypogonadal models, and explore novel androgen regulated metabolic mediators. Developing reliable predictors are crucial to limit therapy to those that have the best prerequisites for a beneficial response and avoid therapy to non-responders and those that are at risk for development of side effects. Developing and optimizing potential predictors may have dramatic effects on the quality of life of the individual and on health care spending by the society. Considering the average lifespan of males is 4-6 years (in some societies up to 15 years) shorter than women, which indicate that important information and benefits can be gained in studying and treating the males
Karolinska Universitetssjukhuset Huddinge
141 86 Stockholm, Sweden
Stefan Arver, email: firstname.lastname@example.org
Phone: +46 (0) 8-585 868 76
Christoffer Rahm (Priotab) email: email@example.com