Effect of thyroid hormones administration on urinary endogenous steroid profile of the athlete biological passport.

This work focused on the possible alterations of the markers of the steroidal module of the athlete biological passport, considering samples of athletes declaring and not-declaring the supplementation of thyroid hormones (TH) in the Doping Control Form (DCF). Concentrations of 5α-androstane-3α,17ß-diol (5α-Adiol), 5ß-androstane-3α,17ß-diol (5ß-Adiol), testosterone (T), androsterone (A), etiocholanolone (Etio), epitestosterone (E), pregnanediol (PD), dehydroepiandrosterone (DHEA), and 11ß-hydroxy-androsterone (OHA) were calculated using internal standards and external calibration by gas chromatography-tandem mass spectrometry. Also, ratios between the above biomarkers were also estimated. The data set was composed of samples from females and males declaring and not-declaring TH supplementation in the DCF. To corroborate these observations, a controlled urinary excretion study was carried out with multiple doses of sodium liothyronine (T3). Female data showed significant differences for the concentrations of 5α-Adiol, A, DHEA, E, OHA, and T and the ratio A/Etio between FD and FND groups, whereas the male groups only showed significant differences in OHA concentration. In both cases, males and females declaring the consumption of levothyroxine showed narrower data distribution and diminished percentiles from 17% to 67% with respect to the not-declaring corresponding groups (p < 0.05). Concentrations of 5α-metabolites showed a higher depression for the FND, and both FD and MD groups showed a peculiar behavior for the PD concentrations. The controlled study agreed with the observations, mainly for the female group with significant differences for concentrations of E, Etio, 5α-Adiol, and 5ß-Adiol after TH administration. The interpretation of the steroid markers of the ABP should consider TH administrations.

Usefulness of serum androgen isotope ratio mass spectrometry (IRMS) to detect testosterone supplementation in women.

The detection of testosterone intake is facilitated by monitoring the urinary steroid profile in the athlete biological passport. This technique can be used with confidence to identify target samples for isotope ratio mass spectrometry. Regrettably, most research has been performed on male subjects resulting in a method that does not account for females' steroid concentration and/or variation. This study evaluates the usefulness of the carbon isotope ratio (CIR) in serum of female subjects. Two steroid sulphates are targeted in serum, androsterone and epiandrosterone. Both exhibit statistically significant depletion of their CIR after 10 weeks of daily (10 mg) transdermal testosterone administration. Of the 21 female subjects, samples from six individuals were identified as adverse analytical findings; additionally, four were found atypical considering the serum CIR. The urinary athlete biological passport was not sufficiently sensitive to identify target serum samples for isotope ratio mass spectroscopy. Of the six with a suspicious passport, only two could be confirmed using the serum CIR of androsterone and epiandrosterone. This study shows that CIR analysis in serum cannot be considered the sole confirmatory solution to detect testosterone doping in women due to low sensitivity. However, this analysis has the potential to be used as a complementary method in certain situations to confirm exogenous testosterone in women.

16α-Bromoepiandrosterone as a new candidate for experimental diabetes-tuberculosis co-morbidity treatment.

Tuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-ß-hydroxysteroid dehydrogenase type 1 (11-ßHSD1). 11-ßHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-ß-hydroxysteroid dehydrogenase type 2 (11-ßHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-ßHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-ßHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-ßHSD1 expression while increasing 11-ßHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.

Characterization of eQTLs associated with androstenone by RNA sequencing in porcine testis.

Characterization of genetic variants affecting genome-wide gene expression levels (expression quantitative trait loci or eQTLs) in pig testes may improve our understanding of genetic architecture of boar taint (an animal welfare trait) and helps in genome-assisted or genomic selection programs. The aims of this study were to identify eQTLs associated with androstenone, to find candidate eQTLs for low androstenone, and to validate the top eQTL by reverse transcriptase quantitative PCR (RT-qPCR). Gene expression profiles were obtained by RNA sequencing in testis from Danish cross-bred pigs and genotype data by 80K single nucleotide polymorphism panel. A total of 262 eQTLs [false discovery rate (FDR) < 0.05] were identified by using two software packages: Matrix eQTL and Krux eQTL. Of these, 149 cis-acting eQTLs were significantly associated with androstenone concentrations and gene expression (FDR < 0.05). The eQTLs were associated with several genes of boar taint relevance including CYP1A2, CYB5D1, and SPHK2. One eQTL gene, AMPH, was differentially expressed (FDR < 0.05) and affected by chicory. Five candidate eQTLs associated with low androstenone concentrations were discovered, including the top eQTL associated with CYP1A2. RT-qPCR confirmed target gene expression to be significantly (P < 0.05) different based on eQTL genotypes. Furthermore, eQTLs were enriched as QTLs for 15 boar taint related traits from the PigQTLdb. This is the first study to report eQTLs in testes of commercial crossbred pigs used in pork production and to reveal genetic architecture of boar taint. Potential applications include development of a DNA test and in advanced genomic selection models for boar taint.

The effect of tea consumption on the steroid profile.

Green tea (GT), along with its flavonol epigallocatechin-3-gallate (EGCG), has shown to inhibit the UGT2B17 isoenzyme, which is highly involved in the glucuronidation of testosterone (T) and its metabolites. Since the steroid profile (SP) is composed of urinary concentrations of T and related metabolites excreted in both the free and the glucuronide fractions, GT consumption could alter the SP, leading to misunderstanding in doping controls. The aim of the present work was to study the effect of GT consumption on the SP. This study was performed with 29 male volunteers, which could be classified in 2 arms depending on their T/E values (0.12 ± 0.02, n = 12; 1.64 ± 0.90, n = 17). The clinical protocol was designed to evaluate the effect of GT administration on the SP biomarkers. Participants were asked to consume GT with a high content of EGCG for 7 days (5 GT beverages along the whole day for days 1-6 and 9 GT beverages on day 7, corresponding to 520 and 936 mg/day of EGCG, respectively). Urine samples were collected before and during GT consumption at different time periods. The SP was measured using gas chromatography-mass spectrometry. The excretion rates of the SP metabolites did not change after GT consumption. Moreover, the individual evaluation of the subject's steroidal biological passport resulted in normal sequences. The results obtained show that GT consumption does not distort the establishment of normal ranges of SP parameters. Therefore, GT consumption does not need to be considered a confounding factor in the SP evaluation.

Androst-5-ene-3ß,7α/ß,17ß-triols, their plasma levels and dependence on the hypothalamic-pituitary-adrenal axis.

Androst-5-ene-triols are metabolites of dehydroepiandrosterone, the most abundant steroid hormone in human circulation. Many observations in rodents have demonstrated the anti-inflammatory and immune modulating activity of 7ß-hydroxy-androst-5-enes, and on the basis of these experiments androst-5-ene-3ß,7ß,17ß-triol is considered as a potential agent in the treatment of autoimmune diseases. In contrast to the fairly abundant information on the levels and effects of androst-5-ene-triols in experimental animals and of their the pharmacological perspective, little is known about androst-5-ene-3ß,7α/ß,17ß-triols circulating in human blood, their regulation by the hypothalamo-pituitary-adrenal axis, or their daily concentration variability. Here we provide some data on androst-5-ene-3ß,7α/ß,17ß-triol concentrations under various conditions in men and women.

Reduction of androstenone perception in pan-fried boar meat by different masking strategies.

BACKGROUND: Consumers highly sensitive to androstenone María (AND) will probably reject meat from entire male pigs, which tends to have high levels of this hormone. To avoid this, the effect of different masking strategies (sprinkling with mixed spices or fennel, marinating and breading with garlic-parsley or curry) on the sensory parameters of pork loin chops obtained from entire animals with high levels of AND (1.0-2.9 mg kg-1 AND in fat) and castrated animals (<0.4 mg kg-1 AND in fat), both with low levels of skatole (<0.1 mg kg-1 skatole in fat) was investigated. RESULTS: The garlic-parsley breadcrumbs led to the highest reduction in the perception of AND compared with the other masking strategies used, and preserved the juiciness of the product. There was a negative correlation between AND and fat content. CONCLUSION: AND odor and flavor can be reduced in meat from entire male pigs by using suitable strategies, the best strategy being the garlic-parsley breadcrumbs. © 2017 Society of Chemical Industry.

The neurosteroid dehydroepiandrosterone sulfate, but not androsterone, enhances the antidepressant effect of cocaine examined in the forced swim test--Possible role of serotonergic neurotransmission.

One of the mechanisms of cocaine's actions in the central nervous system is its antidepressant action. This effect might be responsible for increased usage of the drug by individuals with mood disorders. Higher endogenous levels of the excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS) were reported to correlate with successful abstinence from cocaine use in addicts, but a clinical trial showed that supplementation with a high dose of DHEA increased cocaine usage instead. Such ambiguous effects of DHEA(S) could potentially be linked to its influence on the antidepressant effect of cocaine. In this study we tested DHEAS and its metabolite, androsterone, for interactions with cocaine in animal model of depression (forced swim test) and examined the effects of both steroids and cocaine on serotoninergic neurotransmission. All substances were also tested for influence on locomotor activity. A cocaine dose of 5mg/kg, which had no significant effect on locomotor activity, was chosen for the forced swim test. Neither DHEAS nor androsterone showed any antidepressant action in this test, while cocaine manifested a clear antidepressant effect. Androsterone slightly reduced the antidepressant influence of cocaine while DHEAS markedly, dose-dependently enhanced it. Such an effect might be caused by the influence of DHEAS on serotonin neurotransmission, as this steroid decreased serotonin concentration and turnover in the striatum. When DHEAS and cocaine were administered together, the levels of serotonin in the striatum and hippocampus remained unchanged. This phenomenon may explain the additive antidepressant action of DHEAS and cocaine and why co-administration of DHEAS and cocaine increases drug use.

Prohormone supplement 3ß-hydroxy-5α-androst-1-en-17-one enhances resistance training gains but impairs user health.

Prohormone supplements (PS) are recognized not to impart anabolic or ergogenic effects in men, but the research supporting these conclusions is dated. The Anabolic Steroid Control Act was amended in 2004 to classify androstenedione and 17 additional anabolic compounds as controlled substances. The viability of PS that entered the market after that time have not been evaluated. Seventeen resistance-trained men (23 ± 1 yr; 13.1 ± 1.5% body fat) were randomly assigned to receive either 330 mg/day of 3ß-hydroxy-5α-androst-1-en-17-one (Prohormone; n = 9) or sugar (Placebo; n = 8) per os and complete a 4-wk (16 session) structured resistance-training program. Body composition, muscular strength, circulating lipids, and markers of liver and kidney dysfunction were assessed at study onset and termination. Prohormone increased lean body mass by 6.3 ± 1.2%, decreased fat body mass by 24.6 ± 7.1%, and increased their back squat one repetition maximum and competition total by 14.3 ± 1.5 and 12.8 ± 1.1%, respectively. These improvements exceeded (P < 0.05) Placebo, which increased lean body mass by 0.5 ± 0.8%, reduced fat body mass by 9.5 ± 3.6%, and increased back squat one repetition maximum and competition total by 5.7 ± 1.7 and 5.9 ± 1.7%, respectively. Prohormone also experienced multiple adverse effects. These included a 38.7 ± 4.0% reduction in HDL (P < 0.01), a 32.8 ± 15.05% elevation in LDL (P < 0.01), and elevations of 120.0 ± 22.6 and 77.4 ± 12.0% in LDL-to-HDL and cholesterol-to-HDL ratios, respectively (both P < 0.01). Prohormone also exhibited elevations in serum creatinine (19.6 ± 4.3%; P < 0.01) and aspartate transaminase (113.8 ± 61.1%; P = 0.05), as well as reductions in serum albumin (5.1 ± 1.9%; P = 0.04), alkaline phosphatase (16.4 ± 4.7%; P = 0.04), and glomerular filtration rate (18.0 ± 3.3%; P = 0.04). None of these values changed (all P > 0.05) in Placebo. The oral PS 3ß-hydroxy-5α-androst-1-en-17-one improves body composition and muscular strength. However, these changes come at a significant cost. Cardiovascular health and liver function are particularly compromised. Given these findings, we feel the harm associated with this particular PS outweighs any potential benefit.

Tongkat Ali as a potential herbal supplement for physically active male and female seniors--a pilot study.

Tongkat Ali (Eurycoma longifolia; TA) is known to increase testosterone levels and alleviate aging males' symptoms. This study aimed at investigating TA as an ergogenic supplement for elderly people. Thirteen physically active male and 12 physically active female seniors (57-72 years) were supplemented with 400-mg TA extract daily for 5 weeks. Standard hematological parameters were taken. In addition, the concentrations of total and free testosterone, dihydroepiandrosterone, cortisol, insulin-like growth factor-1, and sex hormone-binding globulin were analyzed. As additional biochemical parameters, blood urea nitrogen and creatine kinase as parameters of kidney function and muscle damage, respectively, as well as the muscle strength by a simple handgrip test were determined. After treatment, hemoglobin, testosterone, and dihydroepiandrosterone concentrations, and the ratio of total testosterone/cortisol and muscle force remained significantly lower in female seniors than in male seniors. Hematocrit and erythrocyte count in male seniors increased slightly but were significantly higher than in female seniors. Treatment resulted in significant increases in total and free testosterone concentrations and muscular force in men and women. The increase in free testosterone in women is thought to be due to the significant decline in sex hormone-binding globulin concentrations. The study affirms the ergogenic benefit of TA through enhanced muscle strength.

Metabolomic profiles in individuals with negative affectivity and social inhibition: a population-based study of Type D personality.

BACKGROUND: Individuals with negative affectivity who are inhibited in social situations are characterized as distressed, or Type D, and have an increased risk of cardiovascular disease (CVD). The underlying biomechanisms that link this psychological affect to a pathological state are not well understood. This study applied a metabolomic approach to explore biochemical pathways that may contribute to the Type D personality. METHODS: Type D personality was determined by the Type D Scale-14. Small molecule biochemicals were measured using two complementary mass-spectrometry based metabolomics platforms. Metabolic profiles of Type D and non-Type D participants within a population-based study in Southern Germany were compared in cross-sectional regression analyses. The PHQ-9 and GAD-7 instruments were also used to assess symptoms of depression and anxiety, respectively, within this metabolomic study. RESULTS: 668 metabolites were identified in the serum of 1502 participants (age 32-77); 386 of these individuals were classified as Type D. While demographic and biomedical characteristics were equally distributed between the groups, a higher level of depression and anxiety was observed in Type D individuals. Significantly lower levels of the tryptophan metabolite kynurenine were associated with Type D (p-value corrected for multiple testing=0.042), while no significant associations could be found for depression and anxiety. A Gaussian graphical model analysis enabled the identification of four potentially interesting metabolite networks that are enriched in metabolites (androsterone sulfate, tyrosine, indoxyl sulfate or caffeine) that associate nominally with Type D personality. CONCLUSIONS: This study identified novel biochemical pathways associated with Type D personality and demonstrates that the application of metabolomic approaches in population studies can reveal mechanisms that may contribute to psychological health and disease.

Laser-induced acoustic desorption/atmospheric pressure chemical ionization mass spectrometry.

Laser-induced acoustic desorption (LIAD) was successfully coupled to a conventional atmospheric pressure chemical ionization (APCI) source in a commercial linear quadrupole ion trap mass spectrometer (LQIT). Model compounds representing a wide variety of different types, including basic nitrogen and oxygen compounds, aromatic and aliphatic compounds, as well as unsaturated and saturated hydrocarbons, were tested separately and as a mixture. These model compounds were successfully evaporated into the gas phase by using LIAD and then ionized by using APCI with different reagents. From the four APCI reagent systems tested, neat carbon disulfide provided the best results. The mixture of methanol and water produced primarily protonated molecules, as expected. However, only the most basic compounds yielded ions under these conditions. In sharp contrast, using APCI with either neat benzene or neat carbon disulfide as the reagent resulted in the ionization of all the analytes studied to predominantly yield stable molecular ions. Benzene yielded a larger fraction of protonated molecules than carbon disulfide, which is a disadvantage. A similar but minor amount of fragmentation was observed for these two reagents. When the experiment was performed without a liquid reagent (nitrogen gas was the reagent), more fragmentation was observed. Analysis of a known mixture as well as a petroleum cut was also carried out. In summary, the new experiment presented here allows the evaporation of thermally labile compounds, both polar and nonpolar, without dissociation or aggregation, and their ionization to predominantly form stable molecular ions.

Seized designer supplement named "1-Androsterone": identification as 3ß-hydroxy-5α-androst-1-en-17-one and its urinary elimination.

New analogues of androgens that had never been available as approved drugs are marketed as "dietary supplement" recently. They are mainly advertised to promote muscle mass and are considered by the governmental authorities in various countries, as well as by the World Anti-doping Agency for sport, as being pharmacologically and/or chemically related to anabolic steroids. In the present study, we report the detection of a steroid in a product seized by the State Bureau of Criminal Investigation Schleswig-Holstein, Germany. The product "1-Androsterone" of the brand name "Advanced Muscle Science" was labeled to contain 100mg of "1-Androstene-3b-ol,17-one" per capsule. The product was analyzed underivatized and as bis-TMS derivative by GC-MS. The steroid was identified by comparison with chemically synthesized 3ß-hydroxy-5α-androst-1-en-17-one, prepared by reduction of 5α-androst-1-ene-3,17-dione with LS-Selectride (Lithium tris-isoamylborohydride), and by nuclear magnetic resonance. Semi-quantitation revealed an amount of 3ß-hydroxy-5α-androst-1-en-17-one in the capsules as labeled. Following oral administration to a male volunteer, the main urinary metabolites were monitored. 1-Testosterone (17ß-hydroxy-5α-androst-1-en-3-one), 1-androstenedione (5α-androst-1-ene-3,17-dione), 3α-hydroxy-5α-androst-1-en-17-one, 5α-androst-1-ene-3α,17ß-diol, and 5α-androst-1-ene-3ß,17ß-diol were detected besides the parent compound and two more metabolites (up to now not finally identified but most likely C-18 and C-19 hydroxylated 5α-androst-1-ene-3,17-diones). Additionally, common steroids of the urinary steroid profile were altered after the administration of "1-Androsterone". Especially the ratios of androsterone/etiocholanolone and 5α-/5ß-androstane-3α,17ß-diol and the concentration of 5α-dihydrotestosterone were influenced. 3α-Hydroxy-5α-androst-1-en-17-one appears to be suitable for the long-term detection of the steroid (ab-)use, as this characteristic metabolite was detectable in screening up to nine days after a single administration of one capsule.

Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17ß-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Role of androgens in women's sexual dysfunction.

OBJECTIVE: Although suspected, androgen deficit in women with sexual dysfunction has never been established. Given that serum testosterone levels are of limited value, we sought to compare total androgen activity in women with and without hypoactive sexual desire disorder (HSDD). Intracellular production in target tissues is the major source of testosterone in older women and can now be measured. Androgen metabolites, specifically androsterone glucuronide (ADT-G), reflect intracellular and ovarian sources of testosterone. Thus, we predicted significantly lowered levels of metabolites in women with sexual dysfunction. METHODS: A detailed assessment of the sexual function of women without depression, without serious relationship discord, or receiving medications affecting sexual function included 121 women with HSDD and 124 sexually healthy community controls. Sexual function was assessed using structured interviews, validated questionnaires, and steroid analysis-mass spectrometry levels of ADT-G, testosterone, and precursor hormones. RESULTS: No group differences in serum levels of testosterone or ADT-G were found. Significantly lower levels of two precursor hormones, dehydroepiandrosterone sulfate and androstene-3ß,17ß-diol, were found in women with sexual dysfunction (P = 0.006 and P = 0.020, respectively). The variability of metabolite and precursor levels was substantial for all women. CONCLUSIONS: Significantly lower levels of the two precursor steroids dehydroepiandrosterone sulfate and androstene-3ß,17ß-diol but not the major androgen metabolite ADT-G were found in women with HSDD. Although the significance of the former awaits further study, androgen deficiency in women with HSDD was not confirmed. Given the unknown long-term effects of testosterone supplementation, women receiving testosterone therapy should be informed that a deficit of testosterone activity in women with HSDD has not been identified.

Sexual dysfunction after premenopausal stage I and II breast cancer: do androgens play a role?

INTRODUCTION: Sexual dysfunction after breast cancer has been attributed to a variety of treatment associated and psychological factors. Data on the role of a treatment-induced decrease of testosterone for the development of sexual problems in breast cancer survivors have remained inconclusive. However, androgen metabolites constitute a more reliable measure for total androgen activity. AIM: To measure levels of total androgen activity in breast cancer patients and to investigate relevant predictors of sexual dysfunction after breast cancer. METHODS: Twenty-nine patients with a premenopausal diagnosis of Stage I or II breast cancer and terminated adjuvant treatment, completed questionnaires on sexuality, quality of relationship, body image, and depression. In addition, blood samples were taken for the analysis of sex steroids. MAIN OUTCOME MEASURES: Female Sexual Function Index (FSFI), Relationship (PFB), Beck Depression Inventory, and European Organization for Research and Treatment of Cancer quality of life questionnaire. Analysis of dihydroepiandrosterone, dihydroepiandrosterone-sulfate, androstenedione, 17beta-diol, testosterone, dihydrotestosterone, androsterone, and ADT-G, 3-alpha-diol-3G, 3-alpha-diol-17G. RESULTS: Low levels of sex steroids reflected the medication-induced postmenopausal status independent of the type of chemotherapy treatment. Sexual dysfunction was present in 68% of the study group. Women with a history of chemotherapy were more affected in all of the FSFI-domains. The only predictor for desire was quality of relationship, while chemotherapy was predictive for problems with arousal, lubrication, orgasm, and sexual pain. Sexual satisfaction and higher FSFI sum scores were predicted by better quality of relationship and no history of chemotherapy, together explaining 54.2% and 49.7% of the variance. CONCLUSIONS: Sexual dysfunction after breast cancer is common and women should be informed properly at an early stage of treatment. Specific interventions have to be offered considering person-related preexisting factors and couples at risk should be supported in the transition to sexual life after breast cancer.

Anti-inflammatory effects and changes in prostaglandin patterns induced by 7beta-hydroxy-epiandrosterone in rats with colitis.

High dose levels of dehydroepiandrosterone and its 7-hydroxylated derivatives have been shown to reduce oxidative stress and inflammatory responses in dextran sodium sulfate (DSS)-induced colitis in rats. Another endogenous steroid, 7beta-hydroxy-epiandrosterone (7beta-hydroxy-EpiA) has been shown to exert neuroprotective effects at much smaller doses. Our aims were to evaluate whether 7beta-hydroxy-EpiA pre-treatment prevents DSS-induced colitis and to determine whether the effects involve changes in anti-inflammatory prostaglandin (PG) D(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) levels. Rats were administered 0.01, 0.1 and 1mg/kg 7beta-hydroxy-EpiA i.p. once a day for 7 days. Thereafter, colitis was induced by administration of 5% DSS in drinking water for 7 days. Levels of the PGs and the expression of cyclooxygenase (COX-2) and PG synthases were assessed during the course of the experiment. Administration of 7beta-hydroxy-EpiA caused a transient increase in COX-2 and PGE synthase expression within 6-15h and augmented colonic tissue levels of 15d-PGJ(2) levels starting at day 2. Treatment with DSS resulted in shortened colon length, depleted mucus in goblet cells and induced oxidative stress. COX-2 and mPGES-1 synthase expression were enhanced and accompanied by increased PGE(2), D(2) and 15d-PGJ(2) production. Although all dose levels of 7beta-hydroxy-EpiA reduced PGE(2) production, only the lowest dose (0.01mg/kg) of the steroid completely prevented colitis damage and tissue inflammation. 7beta-Hydroxy-EpiA pre-treatment prevents the occurrence of DSS-induced colitis through a shift from PGE(2) to PGD(2) production, associated with an early but transient increase in COX-2 expression and a sustained increase in the production of the anti-inflammatory prostaglandin 15d-PGJ(2).

Short term impact of Tribulus terrestris intake on doping control analysis of endogenous steroids.

Tribulus terrestris is a nutritional supplement highly debated regarding its physiological and actual effects on the organism. The main claimed effect is an increase of testosterone anabolic and androgenic action through the activation of endogenous testosterone production. Even if this biological pathway is not entirely proven, T. terrestris is regularly used by athletes. Recently, the analysis of two female urine samples by GC/C/IRMS (gas chromatography/combustion/isotope-ratio-mass-spectrometry) conclusively revealed the administration of exogenous testosterone or its precursors, even if the testosterone glucuronide/epitestosterone glucuronide (T/E) ratio and steroid marker concentrations were below the cut-off values defined by World Anti-Doping Agency (WADA). To argue against this adverse analytical finding, the athletes recognized having used T. terrestris in their diet. In order to test this hypothesis, two female volunteers ingested 500 mg of T. terrestris, three times a day and for two consecutive days. All spot urines were collected during 48 h after the first intake. The (13)C/(12)C ratio of ketosteroids was determined by GC/C/IRMS, the T/E ratio and DHEA concentrations were measured by GC/MS and LH concentrations by radioimmunoassay. None of these parameters revealed a significant variation or increased above the WADA cut-off limits. Hence, the short-term treatment with T. terrestris showed no impact on the endogenous testosterone metabolism of the two subjects.

Glutathione supplements and the skin: An exploratory study and review of the best current evidence

BACKGROUND: Glutathione is an important intracellular anti-oxidant involved in different cellular and body functions. In recent years, glutathione-containing products have become extremely popular as evidenced by the proliferation of these products especially for 'skin whitening'. The investigators conducted this exploratory study in preparation for further investigations to validate the efficacy and safety of glutathione-containing products. OBJECTIVES: 1) To describe the different glutathione products, their claims on efficacy and safety, as advertised on the Internet; 2) To report the best current evidence on the claims of efficacy and safety of glutathione supplements and glutathione-containing products for the skin. METHOD: An online search for glutathione distributors was conducted from February to March 2008 to find out their claims on the efficacy and safety of glutathione-containing supplements or IV glutathione. For the search of the best current evidence on glutathione products, various electronic databases were searched up to September 2008 for any human clinical trials or reports of adverse events. Key informants were also interviewed. RESULTS: From the Internet search, there were 20 brands oftopical glutathione products, 21 oral preparations, and 2 injectable glutathione products. There were also a variety of glutathione formulations available, mainly capsules containg glutathione plus other antioxidants. All products claimed a skin 'whitening' effect. There were no published human clinical trials, whether quasi-experimental or controlled trials (ex. RCTs) supporting the claims of skin whitening or skin rejuvenating effects of glutathione. There was one unpublished randomized controlled trial and one local clinical trial ongoing in the Philippines. No adverse events associated with glutathione products were reported in published literature. Anecdotal reports of adverse effects were gathered during key informant interviews. CONCLUSIONS: The evidence on whitening and skin rejuvenation effects and safety is insufficient because these are based on testimonials and anecdotal reports, all of which are at high risk of bias. The magnitude of glutathione's skin whitening effect nor its side-effects have not yet been established. RECOMMENDATIONS: Good quality, randomized, controlled trials are needed to validate claims of skin 'whitening' from the use of glutathione supplementation or glutathione skin products. Health professionals and consumers should document and report adverse events related to glutathione-containing products for the sake of public safety.

Detection of dehydroepiandrosterone and androsterone in a traditional Chinese herbal product.

Dehydroepiandrosterone (DHEA) and androsterone (ADT) were detected in a traditional Chinese herbal product by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). DHEA and ADT were tentatively identified by comparing their electron ionization (EI) mass spectra with those in the GC-MS Wiley database. A multiple reaction monitoring (MRM) scan was performed in LC-MS/MS to confirm the presence of the DHEA and ADT in the herbal product extract. Both the [M + H]+ and the [M + NH4]+ of DHEA and ADT were selected as the precursor ions. DHEA was detected with ion transitions m/z 306.4 --> 271.2, 306.4 --> 253.3, 289.2 --> 270.9, 289.3 --> 253.1 while ADT was detected with ion transitions m/z 308.5 --> 273.6, 308.5 --> 255.3, 291.5 --> 273.5, 291.5 --> 255.2, which confirmed the presence of the two steroid hormones in the herbal product. Limits of detection (LODs) of 0.2 microg ml(-1) for DHEA and 0.3 microg ml(-1) for ADT were found in methanolic standard solutions when [M +NH4]+ of DHEA and ADT were selected as the precursor ions, which allowed the detection of DHEA and ADT at trace level without time-consuming derivatization.