Verena Mattle

Possible role of cytokine-induced tryptophan degradation in anaemia of inflammation.

Anaemia of inflammation (AI) is a frequent complication in patients suffering from chronic inflammatory disorders including infections, autoimmune and malignant disease. Cytokine imbalance with a shift towards T‐helper (Th)1‐type immune response seems to be important in the pathogenesis of this type of anaemia. Interferon‐γ (IFN‐γ) and tumour necrosis factor‐α may affect the growth and differentiation of erythroid progenitor cells. In macrophages, IFN‐γ strongly induces indoleamine (2,3)‐dioxygenase, an enzyme which degrades tryptophan (trp) to kynurenine (kyn). Trp availability is rate limiting for protein biosynthesis and thus cell growth, including erythropoiesis. In this study, trp and kyn concentrations and their relationship to haemoglobin concentrations and to immune activation was examined in 22 patients with AI. Patients with AI presented with lower trp concentrations than healthy controls of similar age, and a significantly higher kyn to trp ratio, suggesting enhanced trp degradation and, because of a positive correlation with neopterin, immune activation. The kyn to trp ratio was inversely correlated to haemoglobin levels. Thus, the limitation of trp availability to erythroid progenitors may be a key mechanism in cytokine‐mediated inhibition of erythropoiesis, and the therapeutic modulation of indoleamine (2,3)‐dioxygenase and trp levels may be promising targets for AI therapy.

Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system

BACKGROUND The levonorgestrel-releasing intrauterine system (LNG-IUS) is well accepted as an easy-to-use contraceptive with an excellent side-effect profile. It contains a reservoir of 52 mg of levonorgestrel (LNG) with continuous release of the steroid. Its contraceptive use is approved for 5 years. The aim of this study was to determine the plasma concentration of LNG and its variation with time in patients with in-dwelling LNG-IUS Mirena®. STUDY DESIGN In this study, we determined LNG plasma concentrations in 110 women with LNG-IUS at different time points of use. Time from insertion of the system in the study population ranged from 20 days to 11.1 years. Quantitative LNG levels were determined using a validated liquid chromatography-tandem mass spectrometry assay. RESULTS The mean±SD LNG plasma level in all women was 147±59 pg/mL. A highly significant negative correlation between LNG plasma level and LNG-IUS time of use could be demonstrated. In the first year of use, LNG plasma level was as high as 191±71 pg/mL, decreasing to 157±68 pg/mL in the second year and 134±41 pg/mL in the third year. Even after exceeding the recommended period of LNG-IUS use, systemic LNG concentrations were detectable: 133±38 pg/mL in the sixth year, 133±48 pg/mL in the seventh year and 117±45 pg/mL in the eighth year. Furthermore, a significant negative correlation between LNG plasma level and body mass index could be shown. CONCLUSION Systemic LNG concentrations can be found in all patients with LNG-IUS IUS. However, concentrations are much lower than in other forms of LNG application. Moreover, this study demonstrates that a systemic effect of LNG-IUS can also be found after the recommended contraceptive lifespan of 5 years.

Female fertility after cytotoxic therapy--protection of ovarian function during chemotherapy of malignant and non-malignant diseases.

Abstract:  Due to the dramatic improvements in cure and survival of young patients of reproductive age suffering from malignant or systemic disease, the preservation of fertility and ovarian function during cytostatic treatment has become of increased importance during the last decade. Pharmacological therapy with GnRH analogues and the cryopreservation of ovarian tissue are discussed in this context. The value of these treatment procedures and their potential clinical applications are critically reviewed in this article.

Metformin, naltrexone, or the combination of prednisolone and antiandrogenic oral contraceptives as first-line therapy in hyperinsulinemic women with polycystic ovary syndrome

To compare the short-term effects of metformin (M), naltrexone (N), and a combination of OC and prednisolone (OC/Pr) on the metabolic state and the ovarian function of PCOS women, we randomized 29 women to a 3-month course of therapy. We observed significant improvements in hyperandrogenemia and ovulation rates in PCOS women of all three groups, in the absence of changes in the metabolic state, suggesting that insulin resistance in PCOS patients is only one of several factors leading to hyperandrogenemic ovarian failure.

Side effects of pulsatile GnRH therapy for induction of ovulation

Summary Pulsatile administration of GnRH by means of a portable pump is an efficient and practical method for the induction of ovulation as a treatment of infertility in hypothalamic amenorrhea. It represents a replacement therapy based on physiological observations. Since the feedback mechanisms between the ovary and pituitary gland remain intact, it is associated with a very low risk of multiple follicular devel -opment and multiple pregnancies. However, the results obtained with this method are critically dependent upon the correct selection of patients as far as the diagnosis of hypothalamic amenorrhea is con -cerned. If this is the case, pulsatile GnRH therapy is safe, associated with a very low risk of multiple pregnancy and, therefore, has to be considered as the therapy of choice in hypothalamic amenorrhea. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.

GnRH-Analoga@@@Gonadotropin-releasing hormone analogues in chemotherapy: Eine einfache und effektive Therapie bei Chemotherapien?

ZusammenfassungDie Erhaltung der Fertilität und der Ovarialfunktion während einer zytostatischen Therapie hat in den vergangenen Jahren zunehmend an Bedeutung gewonnen. Zurzeit werden verschiedene therapeutische Strategien zum Fertilitätserhalt unter Chemotherapie diskutiert. Die therapeutische Option der pharmakologischen Therapie mit GnRH-Analoga wird im Folgenden kritisch betrachtet.AbstractDue to the dramatic improvements in cure and survival of young patients of reproductive age suffering from malignant or systemic disease, the preservation of fertility and ovarian function during cytotoxic therapy has become of increasing importance during the last decade. Different therapeutic options are discussed in this context. The value of suppressive pharmacological therapy with GnRH analogues is critically reviewed in this article.