Obesity: Nieschlag E

Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC, Anonymous00084, Anonymous00085, Anonymous00086, Anonymous00087, Anonymous00088. · Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, and Los Angeles BioMedical Research Institute, Torrance, CA 90509, USA. · J Androl. · Pubmed #18772485 No free full text.

This publication has no abstract.

Zitzmann M, Nieschlag E. · Institute of Reproductive Medicine, University Clinics, Muenster D-48149, Germany. · J Clin Endocrinol Metab. · Pubmed #17635942 links to  free full text

Abstract: CONTEXT: A reliable form of androgen substitution therapy regarding kinetics, tolerance, and restoration of androgenicity is paramount in hypogonadal men. Intramuscular injection of the long-acting ester testosterone undecanoate (TU) offers a new modality. OBJECTIVE: The objective of the study was to assess the safety of TU regarding metabolic and pharmacogenetic confounders. DESIGN: This was a longitudinal one-arm open observation trial. A minimum of five individual assessments was a prerequisite. Putative modulators of safety parameters entering regression models were nadir and/or delta total testosterone concentrations, body mass index, androgen receptor (AR) gene CAG repeat length, and age. SETTING: The study was conducted at an andrological outpatient clinic. PATIENTS: Patients included 66 hypogonadal men (mean age 38 +/- 9.9 yr). MAIN OUTCOME MEASURES: A total of 515 data time points each related to prostate, erythropoiesis, lipoproteins, and circulation during 118 treatment-years with 1000 mg TU at 10- to 14-wk intervals. RESULTS: Testosterone substitution resulted in significant decrements of serum levels of low-density lipoprotein-cholesterol, resting diastolic and systolic blood pressure, and heart rate. Erythropoiesis was stimulated and concentrations of high-density lipoproteincholesterol increased. Parameters remained stable after four injections. No adverse effects regarding the prostate were observed. Significantly increased hematocrit greater than 50% was predicted by enhanced androgen action (shorter AR CAG repeats per higher testosterone levels). However, insufficient androgen action (longer AR CAG repeats per lower testosterone levels) caused pathological safety parameters (high blood pressure, adverse lipid profiles). In addition, a body mass index 30 kg/m(2) or greater represents a clinically relevant factor for the occurrence of all pathological safety parameters. Risk calculations for obese patients and nonlinear pharmacogenetic models to tailor androgen substitution are presented. CONCLUSIONS: Testosterone substitution with im TU is generally well tolerated. Modifications of androgen action are due to both AR CAG repeats and testosterone levels. Adverse observations are mostly seen in obese patients.

Büchter D, Behre HM, Kliesch S, Chirazi A, Nieschlag E, Assmann G, von Eckardstein A. · Interdisziplinäres Zentrum für Klinische Forschung, Medizinische Fakultät, Institüt für Reproduktionsmedizin, Westfälische Wilhelms-Universität Münster, Germany. · Exp Clin Endocrinol Diabetes. · Pubmed #10612483 No free full text.

Abstract: We investigated in a pilot study the effect of testosterone suppression on lipoprotein metabolism, insulin, and leptin in 10 men who were treated either with cetrorelix, an antagonist of gonadotropin releasing hormone, or with placebo (P). Group C + C (n = 4) was treated with 10 mg cetrorelix as daily subcutaneous injections for five days and with a subsequent injection of 60 mg cetrorelix depot. Group C + P (n = 3) received 10 mg cetrorelix as daily intramuscular injections for five days and a subsequent injection of placebo depot. Group P + P (n = 3) received placebo both as daily and depot injections. Treatment with cetrorelix reversibly suppressed testosterone to castrate levels for three weeks in group C + C and for one week in group C + P. Compared to baseline, treatment with cetrorelix increased serum levels of apolipoprotein (apo) A-I, HDL subclass LpA-I, insulin, and leptin. In the group P + P, treatment with placebo was not associated with any change of these parameters. Compared to baseline and group P + P, treatment with cetrorelix in groups C + C and C + P did not lead to considerable or consistent changes in the plasma activities of lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), lipoprotein lipase, and hepatic lipase (HL). Only the pooled data of groups C + C and C + P unraveled small but statistically significant decreases of HL and CETP activities in response to cetrorelix. In conclusion, the small or absent effects of cetrorelix on LCAT, CETP, PLTP, LPL, and HL indicate that testosterone regulates HDL levels by other metabolic pathways. The increases of insulin and leptin in response to cetrorelix suggest that testosterone influences HDL metabolism also via obesity and insulin resistance. These effects, however, are rather in contrast to the HDL raising effect of suppressed testosterone.

Lunenfeld B, Nieschlag E. · Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel. · Aging Male. · Pubmed #17701658 No free full text.

Abstract: The decline, with aging, in serum concentrations of biologically active forms of testosterone in men is an indisputable fact and some men will eventually develop symptoms of late-onset hypogonadism (LOH) with its clinical consequences. LOH reduces quality of life and may pose important risk factors for frailty, changes in body composition, cardiovascular disease, sexual dysfunction and osteoporosis. Testosterone supplementation in cases of LOH will restore serum testosterone levels into the physiologic range; will restore metabolic parameters to the eugonadal state, increase muscle mass, strength, and function; maintaine or improve BMD reducing fracture risk; will improve neuropsychological function (cognition and mood); libido and sexual functioning; and enhance quality of life. The ultimate goals, however, are to maintain or regain a high quality of life, to reduce disability, to compress major illnesses into a narrow age range and to add life to years. To achieve these goals men must also adjust their lifestyle to optimize dietary habits, as well as to exercise and to abstain from smoking life-long. Monitoring these patients is a shared responsibility that cannot be taken lightly. The physician must emphasize to the patient the need for periodic evaluations and the patient must agree to comply with these requirements. The physician's evaluation should include an assessment of the clinical response and monitoring must be tailored to the indications and individual needs of the patient.