Assessment of androgen concentration in women: liquid chromatography–tandem mass spectrometry and extraction RIA show comparable results

Objective: In hypopituitary men, oral delivery of unesterified testosterone in doses that result in a solely hepatic androgen effect enhances protein anabolism during GH treatment. In this study, we aimed to determine whether liver-targeted androgen supplementation induces protein anabolism in GH-replete normal women. Design: Eight healthy postmenopausal women received 2-week treatment with oral testosterone at a dose of 40 mg/day (crystalline testosterone USP). This dose increases portal concentrations of testosterone, exerting androgenic effects on the liver without a spillover into the systemic circulation. Outcome measures: The outcome measures were whole-body leucine turnover, from which leucine rate of appearance (LRa, an index of protein breakdown) and leucine oxidation (Lox, a measure of irreversible protein loss) were estimated, energy expenditure and substrate utilization. We measured the concentration of liver transaminases as well as of testosterone, SHBG and IGF1. Results: Testosterone treatment significantly reduced LRa by 7.1G2.5% and Lox by 14.6G4.5% (P!0.05). The concentration of liver transaminases did not change significantly, while that of serum SHBG fell within the normal range by 16.8G4.0% and that of IGF1 increased by 18.4G7.7% (P!0.05). The concentration of peripheral testosterone increased from 0.4G0.1 to 1.1G0.2 nmol/l (P!0.05), without exceeding the upper normal limit. There was no change in energy expenditure and fat and carbohydrate utilization. Conclusions: Hepatic exposure to unesterified testosterone by oral delivery stimulates protein anabolism by reducing protein breakdown and oxidation without inducing systemic androgen excess in women. We conclude that a small oral dose of unesterified testosterone holds promise as a simple novel treatment of protein catabolism and muscle wasting.

Section: Discussionmentioning

confidence: 85%

Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy

Birzniece

Umpleby

Poljak

et al. 2013

“…The vast majority of laboratories performing a total serum testosterone assay use direct methods without extraction before performing an immunoassay (48,49). In fact, most immunoassays yield values higher than those obtained using gas chromatography coupled with mass spectrometry (GC-MS) or liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) (50,51), which are recommended as gold standard methods for evaluating steroid hormones (52,53).…”

Section: Laboratory and Biomarkersmentioning

confidence: 99%

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Conway¹,

Dewailly²,

Diamanti-Kandarakis³

et al. 2014

568

492

Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

“…Measurement of DHEAS, a hormone of predominantly adrenal origin in women, is not routinely required, although when a neoplastic source of androgen excess is suspected a very high DHEAS concentration may be predictive of an androgen-secreting adrenal cancer (19). The evaluation of steroid hormone profiles, by using liquid chromatography combined with tandem mass spectrometry, a recent technique displaying good precision, sensitivity, and high accuracy, would greatly improve the assessment of androgen excess in patients with PCOS (20,21,22,23).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

European survey of diagnosis and management of the polycystic ovary syndrome: results of the ESE PCOS Special Interest Group's Questionnaire

Conway¹,

Dewailly²,

Diamanti-Kandarakis³

et al. 2014

Background: There is evidence for differences between endocrinologists and other specialists in their approach to diagnosis and management of the polycystic ovary syndrome (PCOS). Objective: A mailed survey consisting of a simple questionnaire aiming to understand current practice for diagnosis and management of the PCOS by specialists across Europe. Methods: The questionnaire consisted of 23 questions grouped to achieve information on i) the general characteristics of the respondents, ii) patients with PCOS seen by endocrinologists, iii) the main diagnostic criteria, iv) biochemical parameters used in the differential diagnosis of hyperandrogenism, v) long-term concerns, and, finally vi) treatment choices. A total of 357 questionnaires representing 13.3% of the members of European Society of Endocrinology (ESE) were available for final analysis; 93% of the respondents were endocrinologists Results: In relation to the diagnostic criteria, respondents were most likely to select menstrual irregularity as the most frequent criteria used for the diagnosis of PCOS although very high rates were achieved for the use of hirsutism and biochemical hyperandrogenism. It therefore appears that the NIH criteria were followed by the majority of respondents. The most frequent biochemical parameters in the differential diagnosis of hyperandrogenism were total testosterone or free androgen index. Obesity and type 2 diabetes were regarded as the principal long-term concerns for PCOS. The most common treatments for patients with PCOS were metformin (33%), lifestyle modification (25%), and oral contraceptives (22%). More direct treatments of infertility include clomiphene citrate alone or in combination with metformin, prescribed by 9 and 23%, respectively, whereas only 6% used other methods for induction of ovulation.