Monitoring testosterone replacement therapy with transdermal gel: when and how?

PURPOSE: Testosterone replacement therapy (TRT) is recommended for the treatment of most cases of male hypogonadism. Transdermal testosterone (T) gels are commonly used in clinical practice; however, there is little evidence concerning how to monitor dosage to bring and maintain serum T levels in the normal physiologic range. METHODS: We examined 30 hypogonadal patients undergoing treatment with 40 mg/day transdermal 2% testosterone gel. After a week from treatment onset, all patients underwent a total of four measurements to assess serum total T, bioavailable T and free T at + 2 h (samples A and A') and + 23 h (samples B and B'). RESULTS: No significant difference was found concerning total, free and bioavailable T between the two samples taken at the same time points (A vs A' and B vs B'). A repeated-measures mixed effects regression model showed significantly lower serum levels of total, free and bioavailable T at + 23 h compared to + 2 h (total T, ß = - 3.050 ± 0.704, p < 0.001; free T, ß = - 85.187 ± 22.746, p < 0.001; bioavailable T, ß = - 1.519 ± 0.497, p = 0.003) without a significant between-sample variability. Serum T > 3.5 ng/ml at + 2 h was reached in 21/30 patients (70%), but only 11 (36.7%) still had adequate serum T at + 23 h. CONCLUSION: Assessment of TRT with transdermal gels at its peak and at its minimum could be useful in providing a finely tailored treatment for hypogonadal men, both preventing supra-physiological levels and maintaining adequate concentrations through the day.

Gender in Endocrine Diseases: Role of Sex Gonadal Hormones.

Gender- and sex- related differences represent a new frontier towards patient-tailored medicine, taking into account that theoretically every medical specialty can be influenced by both of them. Sex hormones define the differences between males and females, and the different endocrine environment promoted by estrogens, progesterone, testosterone, and their precursors might influence both human physiology and pathophysiology. With the term Gender we refer, instead, to behaviors, roles, expectations, and activities carried out by the individual in society. In other words, "gender" refers to a sociocultural sphere of the individual, whereas "sex" only defines the biological sex. In the last decade, increasing attention has been paid to understand the influence that gender can have on both the human physiology and pathogenesis of diseases. Even the clinical response to therapy may be influenced by sex hormones and gender, but further research is needed to investigate and clarify how they can affect the human pathophysiology. The path to a tailored medicine in which every patient is able to receive early diagnosis, risk assessments, and optimal treatments cannot exclude the importance of gender. In this review, we have focused our attention on the involvement of sex hormones and gender on different endocrine diseases.

Clinical presentation and management of patients with primary hyperparathyroidism in Italy.

PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13  years), the remaining 38 (6.3%, age 41 ± 17  years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

Supra-physiological rhGH administration induces gender-related differences in the hypothalamus-pituitary-thyroid (HPT) axis in healthy individuals.

PURPOSE: The use of recombinant human growth hormone (rhGH) is a common habit among athletes. While the effects of rhGH administration have been described with contrasting results in males, no data exist in females to date. The aim of the present study was to evaluate the effects of rhGH administration on TSH, FT4 and FT3 levels and the time requested to return to baseline values after treatment withdrawal. METHODS: Twenty-one healthy trained male and female athletes were treated with 0.03 mg rhGH/kg body mass 6 days/week for 3 weeks. We collected blood samples immediately before the first daily rhGH administration, at 3, 4, 8, 15 and 21 days of treatment and at 3 and 9 days after rhGH withdrawal. RESULTS: In males, rhGH administration induced a significant (p < 0.01) early and stable TSH decrease and IGF-I increase, and a delayed FT4 reduction without FT3 modification, suggesting a central regulatory mechanism. In females, rhGH administration induced a significant (p < 0.01) early and transient TSH decrease and IGF-I increase, and a transient reduction in FT4 without any changes in FT3 concentrations. rhGH withdrawal was associated with a prompt normalization of TSH and FT4 levels in males, while in females the effects of rhGH treatment had already disappeared during the last period of treatment. CONCLUSION: We suggest that rhGH inhibits TSH at central level both in males and females. The pattern of normalization was different in the two genders probably due to gonadal steroids modulation on GH-IGF-I axis.

Italy and Argentina compared: an epidemiological study of occupational diseases.

BACKGROUND: The research presented in this paper analyses the clinic-pathological manifestations and work-related health risks identified among outpatients treated in the hospitals of Rome and Buenos Aires. MATERIALS AND METHODS: The occupational anamnestic data were collected between 2013 and 2014 through questionnaires with specific items aimed at detecting occupational diseases classified by target organ systems in outpatient clinics of cardiology, dermatology, physical medicine, ophthalmology, orthopedics, endocrinology (thyroid and gonads). An inferential statistical analysis was then carried out to evaluate the relationship between nationality, exposure to occupational risks and the prevalence and incidence of the selected pathologies. An univariate statistical analysis was performed for this purpose and, in the case of statistically significant results, a subsequent multivariate analysis was used to evaluate the incidence of occupational risk factors and nationality on the pathology diagnosed in conjunction with other confounding factors such as smoking habits and gender. The total sample consisted of 1090 subjects of both sexes. Risks were grouped into seven categories and diseases into 12 diagnostic groups. We analyzed the correlation between risks and diseases with respect to hospital outpatients and to the total sample then comparing Argentina and Italy's data. RESULTS: Analysis of data revealed a higher prevalence of hypertension and dysmetabolic disorders for DSE (Display Screen Equipment) workers both in Italy and Argentina; however, multivariate analysis showed that smoking represents a confounding factor for this association. A higher prevalence of allergic contact dermatitis (ACD) was found in the population samples of Rome and there appeared to be a correlation between eye disorders/defects and Argentine data source. CONCLUSIONS: Our study suggests the usefulness of collecting occupational anamnestic data from outpatient departments to highlight possible associations between occupational risks, lifestyles and pathologies, so as to implement the appropriate prevention strategies.

Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study.

PURPOSE: Testosterone (T) exerts different effects on the cardiovascular system. Despite this knowledge, the acute vascular effect of androgen remains still poorly understood. METHODS: We investigated the acute effects of T on vascular function in ten men (18-40 years age) with hypogonadism and severe hypotestosteronemia [serum total testosterone (TT) = 0.6 ± 0.3 ng/mL]. In a 4-day double-blind, randomized, placebo-controlled crossover study, we administered 80 mg daily dose of transdermal-T gel (TG) and evaluated endothelial variations with Endopat2000 (reactive hyperemia index, RHI and the augmentation index, AI); also, CAG repeat polymorphism in exon 1 of the androgen receptor gene was investigated. RESULTS: After TG administration, RHI significantly improved at 4 h (p < 0.05), while AI improvement was recorded at 4 and 96 h, also when adjusted for heart rate (AI@75; p < 0.01 and p < 0.001, respectively). Direct relationships between ΔT, ΔDHT and ΔRHI variations (r = 0.37, p < 0.01; r = 0.17, p < 0.05, respectively) as well as between "CAG repeats" length and ΔLnRHI at 96 h (p < 0.03, r (2) = 0.47) were found. An inverse relationship between ΔT and ΔAI (p < 0.01, r = -0.35) and ΔAI@75 (p < 0.01, r = -0.38) were found. CONCLUSION: Administration of TG causes an acute vasodilation and improves arterial stiffness probably due to non-genomic actions of T. Endothelial vasodilatory response was more pronounced depending on higher plasma TT and DHT levels attained. Clinical implications in elderly frail populations are discussed.

Dry Eye Syndrome in Non-Exophthalmic Graves' Disease.

BACKGROUND: The present study aims to assess qualitative and quantitative characteristics of tear film and corneal related impairment and to evaluate the quality of life in a cohort of non-exophthalmic Graves' disease (GD) patients. METHODS: The series comprised 50 eyes from 25 newly diagnosed GD patients with no proptosis. As control group, 56 eyes of 28 thyroid disease-free subjects were enrolled. RESULTS: The results of Schirmer I and II, break-up time, and Oxford scheme showed a significant difference between GD and controls. By ocular surface disease index (OSDI) questionnaire, eleven (44%) GD patients had normal ocular surface, while two (8%) had mild, four (16%) had moderate, and eight (32%) had severe dry eye. The mean score of the OSDI in the GD group was significantly (p < 0.001) higher with respect to the control group. CONCLUSIONS: This study shows that the tear film and cornea are damaged in newly non-exophthalmic GD subjects.

Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers.

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery following CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases. A 100% agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immunohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery.

Testosterone responses to standardized short-term sub-maximal and maximal endurance exercises: issues on the dynamic adaptive role of the hypothalamic-pituitary-testicular axis.

BACKGROUND: Few and conflicting data on the acute adaptive role of the hypothalamic-pituitary-testicular (HPT) axis to sub-maximal endurance exercise exist. AIMS: To investigate the acute HPT axis responses to standardized endurance exercises in a laboratory setting and the correlations between testosterone and classic adaptive hormones variations. SUBJECTS AND METHODS: 12 healthy male volunteers were recruited for this experimental study. Serum PRL, GH, ACTH, LH, cortisol, DHEAS, testosterone [total (TT), calculated free (cFT) and bioavailable (cBioT)], SHBG, and respective ratios, were evaluated before and after a 30-min sub-maximal exercise on cycle ergometer at individual anaerobic threshold (IAT) and a maximal exercise until exhaustion. Blood samples were collected before exercise (30, 15 min and immediately before), immediately after and at different time points during recovery (+15, +30 and +60 min) for hormones assays. Oxygen consumption and lactate concentration were evaluated. RESULTS: Testosterone (TT, cFT and cBioT) acutely increased in all volunteers after both exercises. Testosterone increased in parallel to GH after both exercises and to cortisol only after maximal exercise. Differently from other increased hormones, testosterone increases were not correlated to exercise-intensity-related variables. The anabolic/catabolic steroids ratios were higher after sub-maximal exercise, compared to maximal. CONCLUSIONS: A 30-min sub-maximal endurance exercise acutely increased serum testosterone similarly to maximal exercise, but without cortisol increases. Exercise-related testosterone peaks should be considered adaptive phenomena, but few data on their short- and long-term effects exist. Investigations on the mechanisms of adaptation to exercise in active individuals with physiological or pathological hypo-testosteronemia are warranted.

High sensitive thyroglobulin assay on thyroxine therapy: can it avoid stimulation test in low and high risk differentiated thyroid carcinoma patients?

Thyroglobulin (Tg) is a key marker in the follow-up of differentiated thyroid cancer (DTC). Diagnostic accuracy of serum Tg is higher after TSH stimulation than during thyroxine treatment. However, some studies suggest that TSH stimulation could be not necessary in a large part of patients, if Tg is measured by high sensitive assay under replacement therapy. The aim of this study was to evaluate the need of Tg stimulation test in DTC followed-up by sensitive Tg assay. In a prospective multicenter explorative study, 68 low or high risk patients underwent Tg measurement on thyroxine (ON-LT4-Tg) and after LT4 withdrawal (OFF-LT4-Tg). Undetectable ON-LT4-Tg and OFF-LT4-Tg values (i. e.,<0.15 ng/ml) were found in 56/68 patients, all with negative imaging workup. Twelve subjects had skewed OFF-LT4-Tg: 8 cases had increased ON-LT4-Tg and local recurrence (n=6), distant metastasis (n=1), or benign thyroglossal duct (n=1); the remaining 4 patients had undetectable ON-T4-Tg but detectable OFF-LT4-Tg and neck metastasis was recorded in one of these. By ROC analysis, the most accurate cutoff for ON-LT4-Tg and OFF-LT4-Tg were set at 0.23 ng/ml and 0.70 ng/ml, respectively. A positive ON-LT4-Tg value accurately predicts a positive stimulation test and confers an Odds Ratio of 464 (95% CI from 26.3 to 8 173.2, p<0.0001) to have persistent/recurrent disease. This study shows that DTC patients with ON-LT4-Tg below 0.23 ng/ml by our high sensitive assay should be considered disease free and they can avoid Tg stimulation test. High sensitive Tg assays should be used to better manage DTC patients.

Medullary thyroid nodules by measurement of calcitonin (Ct) in aspiration needle washout in patients with multinodular goiter and moderately elevated serum Ct.

The accuracy of fine needle aspiration cytology (FNAC) is low in medullary thyroid carcinomas (MTC). Recently, a few papers analyzed the measurement of calcitonin (Ct) in washout of the needle after aspiration (WO-Ct) suggesting that this approach may be useful in patients with high serum Ct. Here we reported, for the first time in our best knowledge, 3 patients with multinodular goiter, moderately elevated serum Ct, high value of WO-Ct, and medullary outcome. These findings suggest that in presence of high serum Ct, FNAC should be performed in all nodules, and it should be combined with WO-Ct in all cases.

Measuring calcitonin in washout of the needle in patients undergoing fine needle aspiration with suspicious medullary thyroid cancer.

Calcitonin measurement in washout of the needle after aspiration (WO-Ct) has been rarely evaluated. Here we analyzed the role of WO-Ct in a series of subjects who underwent fine needle aspiration (FNA) with suspicious medullary thyroid cancer (MTC). Twenty-one patients referred following elevated serum calcitonin (S-Ct) or suspicious MTC by cytology. All patients underwent re-evaluation of S-Ct, FNA, and measurement of WO-Ct. S-Ct and WO-Ct were assessed by chemiluminescence assay (IMMULITE 2000, Diagnostic Products Corporation, USA). S-Ct showed elevated value in six subjects (mean 368.8 ± 373.9 pg/ml), of which three cases were cytologically classified as Class 5. WO-Ct obtained in this group (304.0 ± 309.3 pg/ml) was no different from S-Ct. After surgery MTC was confirmed in all patients. In the other 15 patients MTC was excluded by cytology or histology. Two subjects had moderately skewed S-Ct with nonmedullary histology. In the remaining 13 patients S-Ct resulted normal (6.2 ± 5.6 pg/ml) and WO-Ct low (2.9 ± 2.2 pg/ml). Significant (two-tailed P < 0.05, r(2) = 0.27, 95% confidence interval = 0.017-0.81) correlation was found between S-Ct and WO-Ct in nonmedullary patients but not in MTC patients. This study showed that WO-Ct can play a role in diagnosing primary and metastatic MTC. The procedure is easy, cost effective, and should be used in patients undergoing FNA with elevated S-Ct. Further studies and guidelines for the method are needed to use this technique in clinical routine. Until this any institute should use itself cut-off.

Macular translocation with 360 degrees retinotomy for management of retinal pigment epithelial tear: long-term results.

BACKGROUND: To determine long-term functional and morphological changes after full macular translocation (FMT) with 360° retinotomy in patients with retinal pigment epithelium (RPE) tears, in light of the increasing number of reports of this complication following vascular endothelial growth factor (VEGF)-modulating therapy. METHODS: We retrospectively reviewed a consecutive series of six patients with RPE tears secondary to neovascular age-related macular degeneration who underwent FMT with 360° retinotomy between March 2005 and June 2006. Preoperative and postoperative visual acuity, fundus fluorescein angiography (FA) and optical coherence tomography (OCT) were reviewed. RPE tears occurred spontaneously in three cases and after intravitreal triamcinolone in three cases. Preoperative and postoperative best-corrected visual acuity was converted to logarithm of the minimal angle of resolution visual acuity for analysis. RESULTS: Mean postoperative follow-up was 39 months (range 36-50 months). At 12, 24 and 36 months mean visual acuity increased by 6.00 (5.3), 5.57 (5.54) and 6.67 (4.76) lines, respectively. This improvement was maintained at final examination. FA and OCT revealed pigment epithelium atrophy extending to the new fovea in one case only, which also had longer symptom duration. CONCLUSIONS: Long-term follow-up of FMT showed significant improvement in the majority of patients. FMT may be an option for cases of RPE tears of recent onset. Further investigations are necessary to determine FMT's role in tears developing during the course of anti-VEGF therapy.

Does normal thyroid gland by ultrasonography match with normal serum thyroid hormones and negative thyroid antibodies?

Few papers have shown that a hypoechoic appearance of the thyroid gland at ultrasonography (US) is related to a hypofunction and serum positivity of thyroid antibodies (T-Ab). However, it is not ascertained if normal thyroid appearance at US correspond to normal thyroid laboratory tests. The aim of this study was to assess the value of normal thyroid at US in predicting normal thyroid hormones and negative T-Ab in a cohort of 48 adult patients. All patients (37 females and 11 males) were referred to our hospital to undergo their first thyroid US examination, followed by a thyroid function evaluation. All subjects had normal thyroid gland at US. As a control group 65 patients with hypoechoic and inhomogeneous thyroid gland were enrolled. All 48 patients had normal free-T (3) and free-T (4) levels. While 41 patients (85.4%) showed normal TSH, in 7 subjects (14.6%) TSH was elevated and a significant (p < 0.001) difference was recorded between the two groups in mean TSH value. Positive T-Ab value was found in 5 patients (10.4%) and the remaining 43 patients (89.6%) had negative T-Ab. TSH was not significantly correlated with age, thyroid volume or BMI. The multivariate model showed that only BMI was significantly correlated to thyroid volume (p < 0.01, r(2)=0.31). These results showed that normal thyroid recorded by US matches with normal thyroid laboratory assessment to a large degree. These preliminary data need to be confirmed in a prospective study and in a larger series and should suggest the evaluation of thyrotropin and thyroid antibodies in subjects with normal thyroid gland as assessed by US.

Subclinical hyperthyroidism and sport eligibility: an exploratory study on cardiovascular pre-participation screening in subjects treated with levothyroxine for multinodular goiter.

BACKGROUND: Subclinical hyperthyroidism (sHT) affects cardiovascular (CV) morphology and function; whether such changes can impact on sport eligibility is unclear. AIM: This exploratory study evaluated the CV system and sport eligibility in athletes with levothyroxine-induced sHT, in the setting of mandatory pre-participation screening. SUBJECTS AND METHODS: A full, non-invasive CV screening (history and physical examination, 12-lead ECG, echocardiography, 24-hour Holter ECG, exercise stress test) was performed in two groups of untrained female athletes affected by non-toxic multinodular goiter. One group was taking levothyroxine at mildly suppressive doses (TG) whereas the other was untreated (UG). There was also a group of healthy controls (HC). RESULTS: In TG the following characteristics were observed: a) a higher resting heart rate (HR; p<0.01 and p<0.05, vs HC and UG respectively), b) a thicker left ventricular posterior wall (p<0.05 vs HC, and p<0.05 vs HC and UG, respectively), c) a higher mean HR during the 24-hour Holter ECG (p<0.01 and p<0.05, vs HC and UG respectively), and d) a lower achieved maximum work load (p<0.05, vs HC). No differences in the prevalence of cardiac arrhythmias among groups were observed. Sport eligibility was granted to all except one subject in the TG. CONCLUSIONS: Although some alterations were found in athletes with levothyroxine-induced mild sHT, these are probably of limited clinical relevance and they did not contraindicate sport participation in the majority of cases. Future research to address both health risks and the need for specific evaluations (e.g. free thyroxine, TSH, echocardiography) during the preparticipation screening of athletes with sHT is warranted.

Urinary and serum hormones profiles after testosterone enanthate administration in male hypogonadism: concerns on the detection of doping with testosterone in treated hypogonadal athletes.

OBJECTIVE: To describe serum and urinary hormones, androgens metabolites and testosterone/epitestosterone ratio profiles after testosterone administration in male hypogonadal volunteers, and to evaluate their possible usefulness in detecting doping with testosterone in treated hypogonadal athletes. DESIGN: Controlled open label design vs placebo; pharmacokinetic study. PARTICIPANTS: Ten male volunteers affected by severe hypogonadism (serum testosterone <2.31 ng/ml). INTERVENTIONS AND MAIN OUTCOME MEASURES: Serum and urinary parameters were evaluated, by radioimmunoassay and gas chromatography-mass spectrometry, before and at different time points for 7/3 weeks after a single administration of testosterone enanthate (250 mg) or placebo, respectively. RESULTS: As partially known, testosterone administration increased, with great individual variability, urinary concentrations of glucuronide testosterone, androsterone, etiocholanolone, 5alpha-androstane- 3alpha,17beta-diol, 5beta-androstane-3alpha,17beta-diol, testosterone/ epitestosterone and testosterone/LH ratios; and decreased epitestosterone and 5alpha-androstane-3beta,17beta-diol/5beta-androstane- 3alpha,17beta-diol ratio. Serum testosterone and dihydrotestosterone increased in all volunteers, and concentrations higher than the upper reference limits were observed in many volunteers until 2 weeks after testosterone administration. CONCLUSION: Whereas the observed prolonged hyperandrogenism partially limited data interpretation, the report ed characteristics of variation of urinary parameters might be used to suspect testosterone misuse in hypogonadal athletes treated with testosterone enanthate. In this sense, while the actual threshold for tes tos terone/epites tos ter one ratio was confirmed to be of reduced usefulness, we suggest a contemporary evaluation of whole urinary androgen metabolites profile and serum androgens, at specific time points after testosterone enanthate administration. Moreover, an adequate tailoring of treatment, to avoid transitory hyperandrogenism, is highly advisable. Further studies on strategies for detecting doping with testosterone in hypogonadal athletes are warranted.

Efficacy of wrists overnight compression (HT 7 point) on insomniacs: possible role of melatonin?

AIM: Insomnia is a major problem which decreases life quality. Many causes are involved with it and anxiety is often associated. The underlying mechanism is not completely understood, even though different factors seem to be associated. Among them melatonin and its circadian rhythm is thought to have an important role. In addition, acupressure and acupuncture are known to ameliorate insomnia and anxiety, when a specific wrist point is stimulated (HT 7 Shenmen). With these bases, the aim of the present study has been to evaluate the efficacy of an acupressure device, ''H7-insomnia control'', positioned on HT 7 points, during the night, in terms of general health and anxiety levels, together with the evaluation of sleep quality and the urinary melatonin metabolite 6-hydroxymelatonin sulphate determination, in a number of insomniacs. METHODS: Forty patients with insomnia were divided into two groups and randomly received either the H7 or placebo treatments, in a double-blind protocol, for 20 nights. Before and after treatments every subject answered a series of questionnaires (General Health Questionnaire 28 items; State-Trait Anxiety Inventory; Pittsburgh Sleep Quality Index) and collected 24 h urines, divided into two samples of 12 h each. Urinary melatonin metabolite was then determined using a RIA method. RESULTS: Data obtained indicate that the device H7-insomnia control is efficacious to ameliorate quality of sleep and reduce anxiety levels in insomniacs, at a higher extent than in the placebo group. In addition, the 24 hours urinary melatonin metabolite rhythm, obtained at the end of treatment, was considered as being normal in a higher percentage of H7-treated patients, with respect to the placebo group. CONCLUSION: It is plausible to hypothesize that the wrist acupressure device might be considered a valid tool, without adverse effects since it does not contain pharmaceutical products, that is able to naturally ameliorate sleep quality in insomniacs, acting through a not jet completely clarified mechanism, that may involve melatonin.

The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes' VO2max, aerobic, and anaerobic thresholds in normoxia.

Whereas experimental studies showed that in healthy trained subjects, the phosphodiesterase-5 inhibitor (PDE-5i) sildenafil improves exercise capacity in hypoxia and not in normoxia, no studies on the effects of the long half-life PDE-5i tadalafil exist. In order to evaluate whether tadalafil influences functional parameters and performance during a maximal exercise test in normoxia, we studied 14 healthy male athletes in a double-blind cross-over protocol. Each athlete performed two tests on a cycle ergometer, both after placebo or tadalafil (at therapeutic dose: 20 mg) administration. Oxygen consumption (VO2), blood lactate, respiratory exchange ratio, rate of perceived exertion, arterial blood pressure (BP), heart frequency (HR) and oxygen pulse (VO2/HR) were evaluated before exercise, at individual ventilatory and anaerobic thresholds (IVT and IAT), at VO2max and during recovery. Compared to placebo, a single tadalafil administration significantly reduced systolic BP before and after exercise (p < 0.05), decreased VO2/HR at IVT (13.3 +/- 1.8 vs. 14.5 +/- 2.1 mL . beat (-1); p = 0.03), but did not modify individual VO2max, IVT, or IAT. In healthy athletes, 20 mg of tadalafil does not substantially influence physical fitness-related parameters, exercise tolerance, and cardiopulmonary responses to maximal exercise in normoxia; it remains to be verified if higher doses/prolonged use influence health and/or sport performance in field conditions.

Do non-steroidal anti-inflammatory drugs influence the steroid hormone milieu in male athletes?

Prostaglandins modulate the hypothalamus-pituitary-adrenal and -gonadal axis pathways. We explored the effects of a single course of treatment with acetylsalicylic acid (ASA), an inhibitor of prostaglandin synthesis, on the steroid milieu in athletes. Morning plasma cortisol (F), dehydroepiandrosterone sulphate, free-testosterone, testosterone (T) and their ratios were evaluated before and after the administration of either ASA or placebo in twelve male athletes, when affected by minor musculoskeletal trauma and, as control, after a five/six week wash-out in healthy conditions respectively. One tablet of ASA (800 mg), or placebo, was administered two times daily for 10 days during treatment. All the volunteers suspended exercise training during treatment. The results revealed that compared to placebo, plasma F was significantly lower after ASA treatment (p = 0.023). Furthermore, the comparison of hormone's absolute and percentage of variations (Delta and Delta%) between ASA and placebo treatment showed significant differences respectively for DeltaF (p = 0.045), for DeltaT (p = 0.047), for DeltaT/F (p = 0.042), for DeltaF% (p = 0.04) and for DeltaT% (p = 0.049). Our data suggest that in comparison to placebo, a short-term ASA treatment is able to influence the plasma steroid milieu in athletes. Due to the observed variability of the individual hormonal patterns, further research is required to substantiate these findings.