Increase In Free Testosterone Research Articles

Trazodone by epigenetic mechanism can reverse the post finasteride syndrome

The action mechanism of finasteride as inhibitor of the 5alpha-reductase enzyme in the brain could cause an epigenetic change imbalance in the messenger RNA of androgen receptor. The decrease of dihydrotestosterone (DHT) followed by an increase of free testosterone in the brain could in theory cause an imbalance in acetylation and methylation of histones in neurons. So, the post finasteride syndrome would be caused by an epigenetic change in androgen receptors of neurons circuits. Thus, the alpha-adrenergic antagonist properties of trazodone, for example cause priapism, and could change the epigenetic expression of androgen receptors in neuronal circuits responsible for erection and libido. Therefore, through this mechanism, the trazodone could reverse the effect of finasteride on the brain.

Causal relationships between sex hormone traits, lifestyle factors, and osteoporosis in men: A Mendelian randomization study.

Although observational studies have explored factors that may be associated with osteoporosis, it is not clear whether they are causal. Osteoporosis in men is often underestimated. This study aimed to identify the causal risk factors associated with bone mineral density(BMD) in men. Single nucleotide polymorphisms (SNPs) associated with the exposures at the genome-wide significance (p < 5x10-8) level were obtained from corresponding genome-wide association studies (GWASs) and were utilized as instrumental variables. Summary-level statistical data for BMD were obtained from two large-scale UK Biobank GWASs. A Mendelian randomization (MR) analysis was performed to identify causal risk factors for BMD. Regarding the BMD of the heel bone, the odds of BMD increased per 1-SD increase of free testosterone (FT) (OR = 1.13, P = 9.4 × 10-17), together with estradiol (E2) (OR = 2.51, P = 2.3 × 10-4). The odds of BMD also increased with the lowering of sex-hormone binding globulin (SHBG) (OR = 0.87, P = 7.4 × 10-8) and total testosterone (TT) (OR = 0.96, P = 3.2 × 10-2) levels. Regarding the BMD of the lumbar spine, the odds of BMD increased per 1-SD increase in FT (OR = 1.18, P = 4.0 × 10-3). Regarding the BMD of the forearm bone, the odds of BMD increased with lowering SHBG (OR = 0.75, P = 3.0 × 10-3) and TT (OR = 0.85, P = 3.0 × 10-3) levels. Our MR study corroborated certain causal relationships and provided genetic evidence among sex hormone traits, lifestyle factors and BMD. Furthermore, it is a novel insight that TT was defined as a disadvantage for osteoporosis in male European populations.

Increased Free Testosterone Levels in Men with Uncontrolled Type 2 Diabetes Five Years After Randomization to Bariatric Surgery.

Hypogonadism frequently occurs in male patients with type 2 diabetes (T2DM) and is linked to insulin resistance and inflammation. Testosterone levels rise acutely in obese patients following bariatric surgery, though long-term changes have not been investigated in a randomized controlled trial. This study evaluated obese men with T2DM randomized to either bariatric surgery or medical therapy. Testosterone, gonadotropins, body composition, insulin sensitivity, and inflammatory markers were evaluated in 32 patients at baseline and at 5years. Surgical patients had 47.4% increase in free testosterone compared to medical therapy patients who had 2.2% decrease (P=0.013). Increase in free testosterone correlated with reduction in body weight, high-sensitivity C-reactive protein (hsCRP), and leptin levels. Prolonged improvements in testosterone levels after bariatric surgery in T2DM are found to be related to reduction in body weight and adipogenic inflammation.

HIIT produces increases in muscle power and free testosterone in male masters athletes

High-intensity interval training (HIIT) improves peak power output (PPO) in sedentary aging men but has not been examined in masters endurance athletes. Therefore, we investigated whether a six-week program of low-volume HIIT would (i) improve PPO in masters athletes and (ii) whether any change in PPO would be associated with steroid hormone perturbations. Seventeen male masters athletes (60 ± 5 years) completed the intervention, which comprised nine HIIT sessions over six weeks. HIIT sessions involved six 30-s sprints at 40% PPO, interspersed with 3 min active recovery. Absolute PPO (799 ± 205 W and 865 ± 211 W) and relative PPO (10.2 ± 2.0 W/kg and 11.0 ± 2.2 W/kg) increased from pre- to post-HIIT respectively (P < 0.001, Cohen’s d = 0.32−0.38). No significant change was observed for total testosterone (15.2 ± 4.2 nmol/L to 16.4 ± 3.3 nmol/L (P = 0.061, Cohen’s d = 0.32)), while a small increase in free testosterone occurred following HIIT (7.0 ± 1.2 ng/dL to 7.5 ± 1.1 ng/dL pre- to post-HIIT (P = 0.050, Cohen’s d = 0.40)). Six weeks’ HIIT improves PPO in masters athletes and increases free testosterone. Taken together, these data indicate there is a place for carefully timed HIIT epochs in regimes of masters athletes.

Long-Term Effects of a Randomised Controlled Trial Comparing High Protein or High Carbohydrate Weight Loss Diets on Testosterone, SHBG, Erectile and Urinary Function in Overweight and Obese Men.

IntroductionObesity is associated with reduced testosterone and worsened erectile and sexual function in men. Weight loss improves these outcomes. High protein diets potentially offer anthropometric and metabolic benefits, but their effects on reproductive and sexual outcomes is not known.AimTo examine the long-term effects of weight loss with a higher protein or carbohydrate diet on testosterone, sex hormone binding globulin, erectile dysfunction, lower urinary tract symptoms and sexual desire in overweight and obese men.MethodsOne-hundred and eighteen overweight or obese men (body mass index 27–40 kg/m2, age 20–65 years) were randomly assigned to an energy restricted higher protein low fat (35% protein, 40% carbohydrate, 25% fat; n = 57) or higher carbohydrate low fat diet (17% protein, 58% carbohydrate, 25% fat, n = 61) diet for 52 weeks (12 weeks weight loss, 40 weeks weight maintenance). Primary outcomes were serum total testosterone, sex hormone binding globulin and calculated free testosterone. Secondary outcomes were erectile function as assessed by the International Index of Erectile Function (IIEF) (total score and erectile function domain), lower urinary tract symptoms and sexual desire.ResultsTotal testosterone, sex hormone binding globulin and free testosterone increased (P<0.001) and the total IIEF increased (P = 0.017) with no differences between diets (P≥0.244). Increases in testosterone (P = 0.037) and sex hormone binding globulin (P<0.001) and improvements in the total IIEF (P = 0.041) occurred from weeks 0–12 with a further increase in testosterone from week 12–52 (P = 0.002). Increases in free testosterone occurred from week 12–52 (p = 0.002). The IIEF erectile functon domain, lower urinary tract symptoms and sexual desire did not change in either group (P≥0.126).ConclusionsIn overweight and obese men, weight loss with both high protein and carbohydrate diets improve testosterone, sex hormone binding globulin and overall sexual function.Trial RegistrationAnzctr.org.au ACTRN12606000002583

Effects of dutasteride on serum free-testosterone and clinical significance of testosterone changes.

Sixty-two patients with benign prostate hyperplasia (BPH) who were being treated with dutasteride participated in this study. Prostate volume, uroflowmetry, blood tests, the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) were determined before and 1, 3 and 12months after the treatment with dutasteride. Patients were divided into two groups based on changes in serum testosterone after 1month: Group A (>20% increase; n=33) or Group B (<20% increase; n=29). Serum free-testosterone levels were 20.4% higher after 1month and remained constant thereafter. When Groups A and B were compared, baseline free-testosterone levels were significantly lower in Group A, IPSS QOL was significantly better in Group A at 3 and 12months, and no significant differences were observed in uroflowmetry, prostate volume, IPSS or IIEF-5. A univariate analysis identified serum free-testosterone levels and the IPSS storage symptom subscore as significant factors influencing IPSS QOL at 12months, and only the IPSS storage symptom subscore appeared to be independently related to IPSS QOL. These results indicate that dutasteride increases serum free-testosterone levels in BPH patients, particularly with low baseline free-testosterone levels, and the increase in free-testosterone may have further add-on impacts on their urinary tract symptoms.

Effect of Lifestyle Intervention on the Hormonal Profile of Frail, Obese Older Men.

Obesity-associated hypogonadism is hypothesized to be due to the suppressive effect of high estradiol (from an increase in aromatase activity present in the abundant adipose tissue) on the hypothalamic-pituitary-gonadal unit resulting in low testosterone production. Although weight loss has been found to be effective in reducing estradiol and raising testosterone levels in studies of younger men, its effect in frail, obese older men is understudied. Thus, the objective of this study was to determine the effect of lifestyle intervention on hormone levels in frail, obese older men. Randomized controlled trial of lifestyle intervention in frail, obese older men (≥65 yo) for 1 year. University hospital. Forty frail, obese elderly men were randomized, for a 52-week study, to any of the following treatment groups: (1) control group, (2) diet-induced weight loss group (diet group), (3) exercise training group (exercise group), and (4) diet-induced weight loss and exercise training group (diet-exercise group). The objective was to achieve a ~10 % weight loss at 6 months and maintain this weight for an additional 6 months. Physical function was assessed by the modified physical performance testing (modified PPT). Estradiol was measured by radioimmunoassay, testosterone by automated immunoassay, and sex hormone-binding globulin by enzyme-linked immunoassay. After 12 months of intervention, diet alone resulted in a weight loss of -10.1 ± 1.9 kg in the diet group and -9.1 ± 0.9 kg in the diet-exercise group. This resulted in a significant decrease (both p<0.05) in total estradiol compared to baseline among subjects in the diet (-2.5 ± 1.3 pg/ml) and diet-exercise group (-2.2 ± 4.0 pg/ml). Free estradiol index also significantly decreased (both p <0.05) in both the diet (-0.39 ± 0.14 pmol/nmol) and diet-exercise (-0.52 ± 0.12 pmol/nmol) group. Total testosterone significantly increased (p<0.05) in response to diet (71.0 ± 21.0 ng/dl) and diet-exercise (49.9 ± 15.5 pg/ml) resulting in values of 287.0 ± 28.1 ng/dl in the diet and 317.6 ± 33.1 ng/dl in the diet-exercise group. However, because there was a significant increase in sex hormone-binding globulin levels in both the diet and diet-exercise groups, free testosterone index and the changes in free testosterone index were not significant compared to baseline. Regardless of changes in hormonal levels, patients in the diet, exercise, and diet-exercise groups experienced significant improvements in the modified PPT from baseline. Weight loss from lifestyle intervention resulted in significant decreases in total and free estradiol levels in frail, obese older men, but this did not result in a clinically important increase in total testosterone nor a significant increase in free testosterone. Thus, alternative forms of treatment in addition to lifestyle intervention may be necessary to improve the hormonal profile among these patients. Nevertheless, whether further improvement in hormonal profile would result in better physical performance than what can be achieved by lifestyle alone in these subjects remains uncertain.

Influence of a Specialized Trigonella foenum-graecum Seed Extract (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy Menstruating Women, a Randomised Placebo Controlled Study.

The aim of the study was to evaluate the effect of Trigonella foenum-graecum (fenugreek) seed extract on sex hormones and sexual function in healthy menstruating women who reported low sexual drive. This short term, single site, double blind, randomised, placebo-controlled study was conducted on 80 women, aged 20 to 49 years. Participants were randomised to either an oral dose of a standardised T. foenum-graecum seed extract (libifem) at a dose of 600 mg/day or placebo over two menstrual cycles. Dehydroepiandrosterone sulfate, progesterone, androstenedione, total and free testosterone, estradiol (E2), luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and cholesterol were measured at baseline and 8 weeks. The individual aspects of sexual function were measured using the Derogatis interview for sexual functioning and female sexual function index self-administered questionnaires. Stress, fatigue and quality of the relationship with partner were also measured using the PSS (Perceived Stress Scale), MFI-20 (Multidimensional Fatigue Inventory) and DAS (Dyadic Adjustment Scale) quality of life measures, respectively. There was a significant increase in free testosterone and E2 in the active group as well as sexual desire and arousal compared with the placebo group. The results indicate that this extract of T. foenum-graecum may be a useful treatment for increasing sexual arousal and desire in women.

Vitamin K: The missing link to prostate health

Though age-related prostate enlargement is very common in Western societies, and the causes of benign prostate hyperplasia, BPH, have been diligently sought after, there is no biological, mechanistic explanation dealing with the root causes and progression of this very common disorder among men. All treatments to date are based on symptomatic relief, not a fundamental understanding of the cause of the disease. However, recent advances have shown that even subclinical varicoceles, which are more common than generally realized, cause retrograde blood flow from the testes past the prostate gland causing over a 130-fold increase in free testosterone in the veins near the prostate. By treating the varicoceles via embolization of the internal spermatic vein and its communicating and connected vessels the prostate enlargement can be reversed with corresponding symptomatic relief. So, varicose veins in the pampiniform venous plexus, varicoceles, are the direct cause of BPH. But what causes varicoceles?Recent research has uncovered the role of vitamin K in the calcification of varicose veins as well as a role in the proliferation of smooth muscle cells in the media layer of the vein wall. Vitamin K is intimately involved in the formation of varicose veins. The hypothesis is that poor prostate health is essentially a vitamin K insufficiency disorder. By providing vitamin K in the right form and quantity, along with other supporting nutrients and phytochemicals, it is likely that excellent prostate health can be extended much longer, and perhaps poor prostate health can be reversed. A protective role for vitamin K with respect to advanced prostate cancer was already found in the Heidelberg cohort of the EPIC study. This hypothesis can be further evaluated in studies examining the connection between vitamin K and varicoceles, and also by examining the connection between varicoceles and benign prostate hyperplasia. If this hypothesis is found to be true, management of prostate health will be radically altered. Rather than focusing on prostate health as a hormonal imbalance, prostate enlargement will be seen as a result of poor health of the veins in general and the internal spermatic veins in particular. Factors which promote the health of the veins will become a greater focus of research, including the role of vitamin K. Finally, the emerging understanding of the cause of BPH will empower men to take care of their bodies so they can enjoy much better health through their entire lifespan.

TESTOSTERONE CHANGES IN PATIENTS WITH LIVER CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND ITS CORRELATION WITH MELD

Hypogonadism is a common clinical situation in male patients with liver cirrhosis. The aim of the present study was to evaluate the effects of orthotopic liver transplantation on testosterone, free testosterone and sex hormone-binding globulin in male with advanced liver disease and also to determine the relationship of these changes with Model for End-stage Liver Disease (MELD) score. In a prospective study, serum levels of testosterone, free testosterone and sex hormone-binding globulin of 30 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Total testosterone levels increased after orthotopic liver transplantation and the number of patients with normal testosterone levels increased from 18 to 24. Free testosterone mean level in the pre-transplant group was 7.8 pg/mL and increased to 11.5 pg/mL (P = 0.10) and sex hormone-binding globulin level decreased after orthotopic liver transplantation returning to normal levels in MELD ≤ 18 - group (A) (P<0.05). Serum level changes of testosterone, free testosterone and sex hormone-binding globulin are more pronounced in cirrhotic males with MELD ≤ 18. Serum levels of testosterone and free testosterone increase and serum levels of sex hormone-binding globulin decrease after orthotopic liver transplantation.

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.

Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study

The relationship between testosterone and cancer is relatively unexplored. We sought to examine whether testosterone and related hormones are associated with incident prostate, lung, and colorectal cancer. This was a population-based cohort study. Demographic and clinical predictors of cancer, and testosterone, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured between 2001 and 2004 in 3,635 community-dwelling men aged 70 to 88 years (mean 77 years). Cancer notifications were obtained via electronic record linkage until December 31, 2010. During a mean follow-up period of 6.7 ± 1.8 years, there were 297, 104, and 82 cases of prostate, colorectal, and lung cancer. In adjusted competing risks proportional hazards models, each one SD increase in free testosterone was associated with a 9% increase in prostate cancer risk (95% confidence interval [CI], 1.00-1.18), but other hormones were not significantly associated. No significant associations were observed between hormonal parameters and colorectal cancer. Higher total testosterone was associated with lung cancer. Compared with the mean of 15 nmol/L, men with levels of 20 nmol/L were 1.38 times more likely to be cases (95% CI, 1.21-1.57), whereas those with levels of 30 nmol/L were 3.62 times more likely to be cases (95% CI, 2.53-5.18). Higher free testosterone was also associated with lung cancer, though SHBG and LH were not. Associations were maintained after exclusion of current smokers. Higher free testosterone was associated with incident prostate cancer. Higher testosterone levels may also be associated with lung cancer. Further studies should investigate whether these risks apply to men receiving testosterone therapy.

Risk Factors Associated With Cardiovascular Events During Testosterone Administration in Older Men With Mobility Limitation

Testosterone in Older Men with Mobility Limitations Trial found an increased incidence of cardiovascular events in men randomized to testosterone, resulting in enrollment cessation by trial's Data and Safety Monitoring Board. We evaluated changes in gonadal hormones and markers of inflammation and coagulation to elucidate risk factors associated with cardiovascular events. Men aged 65 years or more, with mobility limitation, total testosterone 100-350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Changes in total and free testosterone, estradiol and estrone, C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor-1, and pro-brain naturetic peptide were compared between groups and within the testosterone group between subjects who experienced cardiovascular events and those who did not. Of 209 men randomized (mean age 74 years), gonadal hormones and biomarkers were available in 179 men. Baseline body mass index, gonadal hormones, lipids, Framingham risk scores, and other biomarkers were similar in the two treatment groups. Within the testosterone group, the 6-month increase in free testosterone was significantly greater in men who experienced cardiovascular events than in those who did not [mean (95% confidence interval), 10.6 (4.6-16.7) vs 5.2 (3.0-7.5) ng/dL, p = .05]. In multivariable logistic regression analysis, the change in the serum levels of free testosterone was associated with cardiovascular events. Mobility-limited older men who experienced cardiovascular events had greater increases in serum free testosterone levels than those who did not.

Abdominal Obesity and Metabolic Alterations in the Menopausal Transition

The prevalence of overweight and obesity is strikingly increasing worldwide. Obesity is a major risk factor for non–insulin-dependent diabetes mellitus, cardiovascular diseases, and cancer, and is also associated with various psychosocial consequences. Menopausal transition is associated with unfavorable changes in body composition and abdominal fat deposition, which is accompanied by an increment of insulin resistance/hyperinsulinemia, a decrease in sex hormone-binding globulin levels and, consequently, an increase in free testosterone and greater androgenicity. Central body fat also correlates with deleterious changes in adipokines and inflammation markers like leptin, C-reactive protein, and adiponectin. In addition, the greater deposition of visceral fat in the menopausal transition contributes to the development of an atherogenic lipoprotein profile, which includes high triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations, as well as an increment of small dense low-density lipoprotein (LDL) subfraction, intermediate density lipoproteins (IDL), apolipoprotein (apo) B/apo A-I ratio and lipoprotein(a).

Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome

Variants in the fat mass and obesity–associated gene ( FTO) are associated with obesity and type 2 diabetes mellitus. Women with polycystic ovary syndrome (PCOS) are frequently affected by obesity and impaired glucose tolerance. The aim of this study was to investigate the impact of FTO variants (rs9939609) on metabolic and endocrine parameters in PCOS women. We genotyped the single nucleotide polymorphism rs9939609 (T/A) in 288 PCOS women and performed metabolic and hormonal measurements, oral glucose tolerance test, hirsutism score, and lipometry. The A/T + A/A genotype showed an increased prevalence in overweight/obese PCOS patients (odds ratio [OR] = 1.91, P = .028) and in PCOS women with impaired glucose tolerance (OR = 3.23, P = .009). The A allele was associated with a significant increase in free testosterone ( P = .042), weight ( P = .024), body mass index ( P = .011), 2-hour glucose ( P = .047), 1-hour insulin ( P = .032), and AUCins (area under the curve insulin) ( P = .038). In a logistic regression analysis, the A allele was associated with free testosterone ( P = .025; OR = 1.54; 95% confidence interval, 1.06-2.25; B = 0.86). Total body fat (percentage) ( P = .016), total fat mass ( P = .013), visceral adipose tissue mass ( P = .044), and subcutaneous fat mass ( P = .011) were significantly increased in PCOS women carrying the A allele. We demonstrated that variants within the FTO gene influence hyperandrogenemia and anthropometric parameters in women with PCOS, indicating an important role of FTO variants not only in obesity and diabetes but also in hyperandrogenism in women with PCOS.

Metabolism of exogenous sex steroids and effect on brain functions with a focus on tibolone

Around the menopause, changes in ovarian secretion of steroids result in changes in brain function: hot flushes and sweating later followed by changes in mood, libido and cognition. The relationship between sex steroids and brain functions are reviewed, with focus on hormonal treatments, in particular tibolone, on the postmenopausal brain and on associations between tissue levels and brain functions. Data on steroid levels in human brain are limited. Exogenous oestrogens alone or combined with progestagens reduce hot flushes and sweating, and may favourably affect anxiety, depression and mood. Testosterone alone or combined with E 2 improves libido and mood. Tibolone reduces hot flushes and sweating, and improves mood and libido, but does not stimulate endometrium or breast, like oestrogens. Tibolone is an ideal compound for studying steroid levels and metabolism in brain in view of its structural differences from endogenous steroids and its extensive metabolism required to express its endocrine effects. Brain levels of tibolone metabolites were measured in ovariectomized cynomolgus monkeys receiving tibolone for 36 days. Compared to serum, higher levels of the oestrogenic 3α/β-hydroxytibolone and the androgenic/progestagenic Δ 4-tibolone, and lower levels of sulphated metabolites are found in various brain regions. The high levels of oestrogenic metabolites in the hypothalamus explain hot flush reduction. Combined with the presence of Δ 4-tibolone, the tibolone-induced increase in free testosterone through SHBG reduction explains androgenic effects of tibolone on mood and libido. The levels of tibolone metabolites in the monkey brain support tibolone's effects on brain functions.

Beneficial effect of tibolone on mood, cognition, well-being, and sexuality in menopausal women

Tibolone is a synthetic molecule used extensively for the management of menopausal symptoms, with the proposed additional advantage of enhanced mood and libido. Tibolone, after oral administration, is rapidly converted into 3 major metabolites: 3alpha-hydroxytibolone and 3beta-hydroxytibolone, which have estrogenic effects, and the Delta(4)-isomer, which has progestogenic and androgenic effects. The tissue-selective effects of tibolone are the result of metabolism, of enzyme regulation, and of receptor activation which vary in different tissues. Tibolone seems to be effective on estrogen-withdrawal symptoms such as hot flushes, sweating, insomnia, headache, and vaginal dryness, with results generally comparable to the effects exerted by estrogen-based treatments, and the additional property of a progestogenic activity on the endometrium. As well as relieving vasomotor symptoms, tibolone has positive effects on sexual well-being and mood, and improves dyspareunia and libido. These effects may depend on both estrogenic and androgenic actions exerted at the genital level and in the central nervous system, and on a reduction of sex-hormone-binding globulin and an increase of free testosterone, without affecting Delta-5 androgens levels. Based on the evidence available, tibolone is a valuable treatment option to relieve menopausal complaints, especially in women suffering persistent fatigue, blunted motivation, and loss of sexual desire despite an adequate estrogen replacement.

Monitoring Changes in Performance, Physiology, Biochemistry, and Psychology during Overreaching and Recovery in Triathletes

The present investigation compared responses in previously identified physiological, biochemical, and psychological markers of overreaching in triathletes. Sixteen experienced male triathletes (.VO(2max) [mean +/- SD] = 55.7 +/- 4.9 mL . kg (-1) . min (-1), age = 31.3 +/- 11.7 yr) were divided into matched groups according to physical and performance characteristics, and were randomly assigned to either intensified training (IT) or normal training (NT) groups. Physiological, biochemical, and psychological measures were taken at baseline, following four weeks of overload training and following a two-week taper. The IT group completed 290 % greater physical training load than the NT group during the overload period. The subjects completed a 3-km run time trial (3-km RTT) each week in order to assess the time course of change in endurance performance. 3-km RTT performance was significantly reduced (3.7 +/- 7.5 %; p < 0.05) following four weeks of overload training in the IT group confirming a state of overreaching. During the same period, 3-km RTT performance significantly improved in the NT group (3.0 +/- 1.1 %; p < 0.05). Following the two-week taper, 3-km RTT performance significantly improved in the IT group (7.0 +/- 5.6 %; p < 0.05). Hemoglobin concentration significantly decreased and urea increased in both groups during the overload period (p < 0.05). During the taper hemoglobin normalized with a greater increase in the IT group compared to the NT group (p < 0.05). A significant increase in free testosterone to cortisol ratio was also observed in the IT group compared to the NT group during the taper (p < 0.05). No significant changes were observed for any other biochemical variables during the period of investigation. The RESTQ-76 Sport questionnaire showed an impaired recovery-stress state with increased training load, which improved following the taper in the IT group (p < 0.05). These present results suggest that none of the physiological and biochemical variables measured in this study were effective for the early identification of overreaching in experienced triathletes. However, the RESTQ-76 Sport questionnaire may provide a practical tool for recognizing overreaching in its early stages. These findings have implications for monitoring training status in athletes in a practical training setting.

Effects of 8 Weeks of Supplementation of the Alleged Aromatase Inhibitor Novedex XTTM on Serum Steroid Hormone Profiles and Clinical Safety Markers in Resistance‐Trained Males.

The purpose of this study was to examine the effects of a commercially available aromatase inhibitor (Novedex XT™, Gaspari Nutrition, Neptune, NJ) on serum steroid hormone levels and clinical safety markers. Seventeen resistance trained men (182 ± 6.8 cm, 91.5 ± 14.4kg, 26 ± 4.7yrs, 17 ± 6%) were assigned an 8-wk supplementation protocol consisting of the oral ingestion of either 72 g/d of Novedex XT™ or 72 g/d of placebo. Body composition, blood, and urine samples were taken at baseline and after wks 4, 8, and 11. Using ELISA and EIA, serum samples were assayed for various levels of steroid hormones (total and free testosterone, DHT, estradiol, estrione, estrone, SHBG, LH, and FSH, and cortisol). Data were analyzed by 2-way repeated measures ANOVA. Analyses showed no significant change in clinical safety markers through urine or serum. Significant differences were seen between groups for total testosterone (p = .00), free testosterone (p = .00), DHT (p = .00), and body composition (p = .05). However, no significant difference was seen in estriol (p = .33), estrone (p = .878), or estradiol (p = .08). The results of this study indicated that there was over a 300% increase it total testosterone and a 600% increase in free testosterone, without any associated increases in any of the three estrogen hormones over eight weeks. Therefore, Novedex XT™ appears to significantly elevate endogenous serum testosterone without increasing estrogen, thereby suggesting a plausible role for this nutritional supplement as an effective aromatase inhibitor.

Effects of endurance exercise on free testosterone concentration and the binding affinity of sex hormone binding globulin (SHBG).

Our purpose was to examine the changes in free testosterone concentration following moderately prolonged endurance exercise to determine whether such changes were due to alterations in the binding affinity of sex hormone binding globulin (SHBG). Ten trained men completed control (45 min rest) and exercise (45 min @ 70% VO2max) experimental sessions. Blood samples were collected before (pre-) and immediately after (post-) each of the sessions and analyzed for total testosterone, free testosterone, LH, FSH, cortisol, estradiol, SHBG, epinephrine and norepinephrine. The association constant (Ka) of SHBG for testosterone was assessed to evaluate binding affinity. No significant difference was seen between the pre-control and the pre-exercise session values for any of the measures. However, within the exercise session significant (p<0.01) increases in post samples were evident for total testosterone (+32.0%), free-testosterone (+39.6%), cortisol (+38.0%), norepinephrine (+365.2%) and epinephrine (+225.8%). All other hormonal changes and the responses for Ka were non-significant. The results of the correlation analysis indicated that only norepinephrine was significantly (p<0.05) related to the changes observed in free testosterone (r = +0.92). We conclude that the free testosterone increase with moderately, prolonged endurance exercise was not associated with the change in the binding affinity of SHBG. Furthermore, the data suggest that the exercise induced increase in testosterone involves increased production which may be mediated by sympathetic stimulation of the testicles.