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Sample records for oral testosterone undecanoate

  1. Testosterone Undecanoate-Schering AG.

    PubMed

    2004-01-01

    Schering AG is developing a formulation of testosterone undecanoate [Nebido] for the treatment of testosterone deficiency or hypogonadism. This deficiency can lead to decreased muscle mass, impaired muscle function, osteoporosis, reduced sexual function and mental degeneration. Schering claims that its new formulation provides superior control of blood levels of the drug and permits a longer period of application. Nebido requires only four injections per year, and represents a major improvement for men with testosterone deficiency. Schering AG received approval of its testosterone undecanoate formulation in its first European country, Finland, in November 2003 for the treatment of hypogonadism in men. In July 2004, Schering's testosterone undecanoate formulation completed approval of the European mutual recognition procedure. This approval clears the way for marketing the product (as Nebido) in the large pharmaceutical markets like Germany, France and the UK. The initial phase of the product launch will occur in Finland in October 2004, and in Germany in November 2004. Other European countries will follow in 2005, and following receipt of approval, it will be introduced in the first Latin American and Asian countries. In its 2002 Annual Report, Schering predicted that testosterone undecanoate has the potential to reach peak sales of euro 100 million, 3 years after launch-launch in Europe was at the time anticipated in 2004.

  2. Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5α-reductase by finasteride

    PubMed Central

    Roth, M. Y.; Dudley, R. E.; Hull, L.; Leung, A.; Christenson, P.; Wang, C.; Swerdloff, R.; Amory, J. K.

    2014-01-01

    Summary Oral testosterone undecanoate (TU) is used to treat testosterone deficiency; however, oral TU treatment elevates dihydrotestosterone (DHT), which may be associated with an increased risk of acne, male pattern baldness and prostate hyperplasia. Co-administration of 5α-reductase inhibitors with other formulations of oral testosterone suppresses DHT production and increases serum testosterone. We hypothesized that finasteride would increase serum testosterone and lower DHT during treatment with oral TU. Therefore, we studied the steady-state pharmacokinetics of oral TU, 200 mg equivalents of testosterone twice daily for 7 days, alone and with finasteride 0.5 and 1.0 mg po twice daily in an open-label, three-way crossover study in 11 young men with experimentally induced hypogonadism. On the seventh day of each dosing period, serum testosterone, DHT and oestradiol were measured at baseline and 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 h after the morning dose. Serum testosterone and DHT were significantly increased into and above their normal ranges similarly by all three treatments. Co-administration of finasteride at 0.5 and 1.0 mg po twice daily had no significant effect on either serum testosterone or DHT. Oral TU differs from other formulations of oral testosterone in its response to concomitant inhibition of 5α-reductase, perhaps because of its unique lymphatic route of absorption. PMID:20969601

  3. Dietary fat modulates the testosterone pharmacokinetics of a new self-emulsifying formulation of oral testosterone undecanoate in hypogonadal men.

    PubMed

    Yin, Anthony; Alfadhli, Eman; Htun, Michelle; Dudley, Robert; Faulkner, Sandra; Hull, Laura; Leung, Andrew; Bross, Rachelle; Longstreth, James; Swerdloff, Ronald; Wang, Christina

    2012-01-01

    This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-label, 2-center, 5-way crossover study, a single oral dose of TU containing 300-mg equivalents of T (maximum anticipated human dose per administration) was administered to 16 hypogonadal men with a washout period of at least 5 days between doses. All participants were randomized to receive the TU capsules fasting or 30 minutes after an approximately 800-calorie meal containing 10%, 20%, 30%, or 50% fat. Serial blood samples were collected from 2 hours predose to 25 hours postdose to determine serum T and dihydrotestosterone (DHT) by liquid chromatography tandem mass spectrometry. Administering TU with a meal increased serum T concentrations, with the magnitude of the increase being directly dependent on the amount of fat in the meal. Average and peak serum T concentrations and area under the curve increased as the fat content of the meal was increased. Neither the high-fat meal (50% fat) nor the lower-fat meal (20% fat) showed a significant food effect relative to the normal-fat (Western diet) meal (30% fat). However, administering TU while fasting resulted in 50% or less of the cumulative exposure obtained when administered with 20%- to 50%-fat meals (albeit still substantial). A very-low-fat meal (10% fat) showed a significant food effect relative to the normal meal, but still exceeded the fasting condition by approximately 50%. Serum DHT concentrations showed corresponding increases to the serum T. As expected with the maximum anticipated clinical dose of TU (300 mg T), oral administration of this new formulation with food containing 20% to 50% dietary fat produced T levels at or above the upper range of adult men, and T levels trended higher as dietary fat content increased. Only with a very-low-fat diet (10%) or in a fasted state did a clinically

  4. Dietary Fat Modulates the Testosterone Pharmacokinetics of a New Self-Emulsifying Formulation of Oral Testosterone Undecanoate in Hypogonadal Men

    PubMed Central

    Yin, Anthony; Alfadhli, Eman; Htun, Michelle; Dudley, Robert; Faulkner, Sandra; Hull, Laura; Leung, Andrew; Bross, Rachelle; Longstreth, James; Swerdloff, Ronald; Wang, Christina

    2014-01-01

    This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-label, 2-center, 5-way crossover study, a single oral dose of TU containing 300-mg equivalents of T (maximum anticipated human dose per administration) was administered to 16 hypogonadal men with a washout period of at least 5 days between doses. All participants were randomized to receive the TU capsules fasting or 30 minutes after an approximately 800-calorie meal containing 10%, 20%, 30%, or 50% fat. Serial blood samples were collected from 2 hours predose to 25 hours postdose to determine serum T and dihydrotestosterone (DHT) by liquid chromatography tandem mass spectrometry. Administering TU with a meal increased serum T concentrations, with the magnitude of the increase being directly dependent on the amount of fat in the meal. Average and peak serum T concentrations and area under the curve increased as the fat content of the meal was increased. Neither the high-fat meal (50% fat) nor the lower-fat meal (20% fat) showed a significant food effect relative to the normal-fat (Western diet) meal (30% fat). However, administering TU while fasting resulted in 50% or less of the cumulative exposure obtained when administered with 20%- to 50%-fat meals (albeit still substantial). A very-low-fat meal (10% fat) showed a significant food effect relative to the normal meal, but still exceeded the fasting condition by approximately 50%. Serum DHT concentrations showed corresponding increases to the serum T. As expected with the maximum anticipated clinical dose of TU (300 mg T), oral administration of this new formulation with food containing 20% to 50% dietary fat produced T levels at or above the upper range of adult men, and T levels trended higher as dietary fat content increased. Only with a very-low-fat diet (10%) or in a fasted state did a clinically

  5. Reexamination of Pharmacokinetics of Oral Testosterone Undecanoate in Hypogonadal Men With a New Self-Emulsifying Formulation

    PubMed Central

    SWERDLOFF, RONALD S.; DIAZ-ARJONILLA, MARUJA; DUDLEY, ROBERT E.; FAULKNER, SANDRA; BROSS, RACHELLE; LEUNG, ANDREW; BARAVARIAN, SIMA; HULL, LAURA; LONGSTRETH, JAMES A.; KULBACK, STEVEN; FLIPPO, GREGORY; WANG, CHRISTINA

    2014-01-01

    Many hypogonadal men prefer oral testosterone (T) treatment. Oral T undecanoate (TU) is available in many countries, but not in the United States. We aimed to assess the pharmacokinetics of oral TU in a new self-emulsifying drug delivery system formulation. Pharmacokinetics studies were conducted in 3 parts: 12 hypogonadal men were enrolled in 2 centers for a 1-day dosing study; 29 participants were enrolled from 3 centers for a 7-day dosing study; and 15 participants were enrolled from 1 center for a 28-day dosing study. Serial blood samples for serum sex hormone measurements by liquid chromatography–tandem mass spectrometry were drawn for up to 36 hours after oral TU administration. Mean serum T levels (Cavg) after oral dosing of T 200 mg as TU twice daily with food were within the adult male range in most participants in the 1-, 7-, and 28-day dosing studies but were much lower in the fasting state. The dose-proportional increase in Cavg of serum T after oral T 300 mg twice daily resulted in more participants with supraphysiologic serum T levels. In the 28-day study, trough serum T reached a steady state at day 7. Serum dihydrotestosterone and estradiol levels tracked serum T concentration. Dihydrotestosterone-testosterone ratios increased 3-fold after oral TU administration. Oral T 200 mg twice daily as TU in a new SEDDS formulation may be a viable therapy for hypogonadal men. PMID:21474786

  6. Use of isotope ratio mass spectrometry to detect doping with oral testosterone undecanoate: inter-individual variability of 13C/12C ratio.

    PubMed

    Baume, Norbert; Saudan, Christophe; Desmarchelier, Aurélien; Strahm, Emmanuel; Sottas, Pierre-Edouard; Bagutti, Carlo; Cauderay, Michel; Schumacher, Yorck Olaf; Mangin, Patrice; Saugy, Martial

    2006-05-01

    The metabolic effect of multiple oral testosterone undecanoate (TU) doses over 4 weeks was assessed in seven voluntary men. The protocol was designed to detect accumulation of the substance by choosing the appropriate spot urines collections time and to study the urinary clearance of the substance after weeks of treatment. Urines were analysed by a new GC/C/isotope ratio mass spectrometry (IRMS) method to establish the delta(13)C-values of testosterone metabolites (androsterone and etiocholanolone) together with an endogenous reference compound (16(5alpha)-androsten-3alpha-ol). The significant differences in inter-individual metabolism following TU intake was illustrated by large variations in delta(13)C-values of both T metabolites (maximum Deltadelta(13)C-values = 5.5 per thousand), as well as by very stable longitudinal T/E profiles and carbon isotopic ratios in the first hours following administration. According to T/E ratios and delta(13)C-values, the washout period after 80 mg TU intake was less than 48 h for all subjects and no accumulation phenomenon was observed upon chronic oral administration.

  7. Proteomic analysis of testis biopsies in men treated with injectable testosterone undecanoate alone or in combination with oral levonorgestrel as potential male contraceptive.

    PubMed

    Cui, Yugui; Zhu, Hui; Zhu, Yefei; Guo, Xuejiang; Huo, Ran; Wang, Xinghai; Tong, Jiansun; Qian, Lixin; Zhou, Zuomin; Jia, Yue; Lue, Yan-He; Hikim, Amiya Sinha; Wang, Christina; Swerdloff, Ronald S; Sha, Jiahao

    2008-09-01

    Treatment with injectable testosterone undecanoate (TU) alone or in combination with oral levonorgestrel (LNG) resulted in marked decreases in sperm concentrations. In this study, we used proteomic analyses to examine the cellular/molecular events occurring in the human testis after TU or TU + LNG treatment. We conducted a global proteomic analysis of the human testicular biopsies before and at 2 weeks after TU alone or TU + LNG treatment. Proteins showing significant changes in expression were identified and analyzed. As a result, 17 and 46 protein spots were found with significant differential expression after the treatment with TU alone and TU + LNG, respectively. TU treatment changed the expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), proteasome inhibitor PI31 subunit (PSMF1), and superoxide dismutase [Mn] mitochondrial precursor (SOD2). These proteins inhibit "assembly", induce cell death, and promote compensatory "cell survival" in the testis. After TU + LNG treatment, "proliferation/cell survival" and "apoptosis/death" were the predominant responses in the testis. TU + LNG treatment inhibited the expression of Prolyl 4-hydroxylase beta subunit (P4HB) and Annexin A2 (Annexin II). These proteins are involved in apoptosis and cell proliferation, respectively. TU + LNG treatment also enhanced the expression of SOD2 and Parvalbumin alpha (Pvalb). These two proteins may protect testicular cells against apoptosis/death and promote cell survival. In conclusion, TU and TU + LNG treatments suppress spermatogenesis through different pathways by changing the expression of different proteins. hnRNP K, PSMF1, SOD2, P4HB, Annexin II, and Pvalb, are key proteins that may be early molecular targets responsible for spermatogenesis suppression induced by hormone treatment.

  8. Anaphylaxis Triggered by Benzyl Benzoate in a Preparation of Depot Testosterone Undecanoate

    PubMed Central

    Ong, Gregory S. Y.; Somerville, Colin P.; Jones, Timothy W.; Walsh, John P.

    2012-01-01

    We report the first case of an anaphylactic reaction to Reandron 1000 (depot testosterone undecanoate with a castor oil and benzyl benzoate vehicle). While considered to have a favourable safety profile, serious complications such as oil embolism and anaphylaxis can occur. In our patient, skin testing identified benzyl benzoate to be the trigger, with no reaction to castor oil or testosterone undecanoate components. As benzyl benzoate exists in multiple pharmaceuticals, foods, and cosmetics, individual components of pharmaceuticals should be tested when investigating drug allergies. Doctors should be alert to the potential for serious reactions to any of the components of Reandron 1000. PMID:22272209

  9. Testosterone undecanoate improves lipid profile in patients with type 1 diabetes and hypogonadotrophic hypogonadism.

    PubMed

    Chillarón, Juan J; Fernández-Miró, Mercè; Albareda, Mercè; Fontserè, Sara; Colom, Cristina; Vila, Lluís; Pedro-Botet, Juan; Flores Le-Roux, Juana A

    2016-09-30

    Testosterone deficiency (Td) has been associated with the metabolic syndrome. Few studies have evaluated this condition in type 1 diabetes (T1D). The primary aim of this study was to evaluate the effectiveness of testosterone undecanoate (TU) on insulin sensitivity, glycemic control, anthropometric parameters, blood pressure and lipid profile in patients with Td and T1D. We performed a randomized placebo-controlled multicenter study.

  10. [Study on preparation of testosterone undecanoate ethosomes and its in vitro transdermal penetration].

    PubMed

    Meng, Shu; Yang, Li-Qun; Ma, Li-Ying; Guo, Jing; Li, Miao; Yang, Dan

    2013-05-01

    Ethosomes, as a new vector for transdermal drug delivery, could obviously improve the transdermal penetration of drugs. In this study, we prepared testosterone undecanoate ethosomes, with TU ethosomes as the basic remedy, to determine its appearance, particle size, entrapment efficiency (EE) and membrane fluidity. Meanwhile, a transdermal test was conducted in mice, in order to determine the permeability characteristics of ethosomes as a vector for transdermal drug delivery, and compare transdermal behaviors of TU ethosomes, liposomes and their ethanol solutions.

  11. Treatment of sexual dysfunction of hypogonadal patients with long-acting testosterone undecanoate (Nebido).

    PubMed

    Yassin, Aksam A; Saad, Farid

    2006-12-01

    Recently, testosterone undecanoate (TU), a new parenteral testosterone (T) preparation has been introduced. Two of its distinctive features are (a) its prolonged action: after two initial loading injections 6 weeks apart, usually only one injection every 12 weeks is needed (b) over the full interval between two injections, plasma T levels are in the physiological range. New research presents convincing evidence that T has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, which is, at least, in part reversible upon androgen therapy. Our studies with TU demonstrated that venous leakage could be corrected with T treatment in a number of patients. We further could show that sexual functions, in a substantial number of elderly men, can be restored with treatment with T only. So, these results argue for determination of T levels in elderly men with sexual problems. If the levels are subnormal, T treatment is warranted.

  12. Effectiveness and tolerability of parenteral testosterone undecanoate: a post-marketing surveillance study.

    PubMed

    Wolf, Jan; Keipert, Dieter; Motazedi, Heiko; Ernst, Michael; Nettleship, Joanne; Gooren, Louis

    2017-08-16

    This observational post-marketing study of parenteral testosterone undecanoate (TU) in a non-selected population aimed to: examine the effectiveness of TU as treatment of hypogonadism; record adverse drug reactions (ADR) quantitatively particularly regarding polycythemia, prostate safety and cardiovascular-related metabolic risk factors; and verify whether recommended injection intervals apply to routine clinical practice. Eight hundred and seventy subjects from 259 outpatient units scheduled to visit the clinic six times were included. Effectiveness and tolerability of TU administration were assessed on a 4-point scale. Body weight, waist girth, blood pressure, hemoglobin levels, hematocrit, prostate-specific antigen (PSA), and digital rectal prostate examination were assessed. Over 90% of subjects completed the observational duration of 52.8 ± 9.7 weeks (mean ± SD) and 56% judged effectiveness as very good, 30.8% as good. 63.1% judged tolerability as very good, and 24.4% as good. No adverse effects on indicators of cardiovascular risk were observed. Polycythemia occurred in one subject and a supranormal hematocrit in one subject. Four subjects developed supranormal PSA levels. Prostate carcinoma was found in one subject, one subject had recurrence of a previously surgically treated prostate carcinoma, and the other two showed no indication of malignancy. Parenteral TU is safe, effective, and well-tolerated in clinical practice proving a good therapeutic option for hypogonadism.

  13. Factors influencing time course of pain after depot oil intramuscular injection of testosterone undecanoate.

    PubMed

    Sartorius, Gideon; Fennell, Carolyn; Spasevska, Sasa; Turner, Leo; Conway, Ann J; Handelsman, David J

    2010-03-01

    Pain following depot intramuscular (IM) injection of oil vehicle-based drugs has been little studied. This study aimed to determine prospectively the prevalence, determinants, severity and functional consequences of pain during the week after IM injection of 1 000 mg testosterone undecanoate (TU) in a 4-mL castor oil vehicle. Androgen-deficient men receiving regular T replacement therapy at an academic andrology clinic were recruited to report pain scores using a coloured visual linear analogue scale at seven times over the first day and daily for a week after a deep IM gluteal injection. The time course and covariables influencing pain scores were analysed by mixed model analysis of variance (ANOVA). Following 168 injections in 125 men, pain was reported by 80% of men, peaking immediately after injection, reaching only moderate severity, lasting 1-2 days and returning to baseline by day 4. The pain required little analgesic use and produced minimal interference in daily activities. The time course of pain scores was reproducible in the 43 men who underwent two consecutive injections. Pain was more severe in men who had an earlier painful injection, but less severe in older and more obese men. There were negligible differences in post-injection pain experience between experienced nurses administering injections. Deep IM gluteal injection of depot TU in 4-mL castor oil is well tolerated and post-injection pain is influenced by earlier painful injection experience, as well as age and obesity.

  14. Circulating prolactin and its response to TRH following administration of testosterone undecanoate in normal men.

    PubMed

    Kicovic, P M; Luisi, M; Franchi, F; Krempl, S

    1978-10-01

    To investigate the effect of orally administered testosterone undercanoate (TU) on circulating prolactin (PRL) and PRL response to TRH stimulation, 8 eugonadal male volunteers, aged 19--30, presenting with normal plasma levels of FSH, LH, testosterone (T), estradiol (E2) and PRL, were given 120 mg/day of TU for 6 days. Plasma PRL levels were measured daily during the pre-treatment phase (3 days), treatment phase (6 days) and post-treatment phase (3 days) by radioimmunoassay. The TRH Test (200 micrograms iv) was done on the 3rd day of the pretreatment phase and on the treatment phase. No significant changes in circulating PRL levels or in PRL response to TRH stimulation were observed. Plasma T and E2 levels showed a slight, but not significant tendency to increase, while gonadotropin levels remained unchanged.

  15. Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial

    PubMed Central

    Tong, Seng-Fah; Ng, Chirk-Jenn; Lee, Boon-Cheok; Lee, Verna-KM; Khoo, Ee-Ming; Lee, Eng-Giap; Tan, Hui-Meng

    2012-01-01

    This study aimed to investigate the effect of intramuscular injection of testosterone undecanoate on overall quality of life (QoL) in men with testosterone deficiency syndrome (TDS). A randomized controlled trial over a 12-month period was carried out in 2009. One hundred and twenty men aged 40 years and above with a diagnosis of TDS (serum total testosterone <12 nmol l−1 and total Aging Male Symptom (AMS) scores ≥27) were invited to participate. Interventions comprised intramuscular injection of either placebo or 1000 mg testosterone undecanoate, given at weeks 0, 6, 18, 30 and 42. This paper presents the secondary analysis of QoL changes measured in the scores of Short-Form-12 (SF-12) scale at baseline, weeks 30 and 48 after the first injection. A total of 56/60 and 58/60 men from the active treatment and placebo group, respectively, completed the study. At week 48, before adjusting for baseline differences, the QoL of men in the treatment group improved significantly in five out of the eight domains on SF-12. The physical health composite scores improved 4.0 points from a baseline of 41.9±7.0 in the treatment group compared to 0.8 point from a baseline of 43.7±7.1 in the placebo group (F=3.652, P=0.027). The mental health composite scores improved 4.4 points from a baseline of 37.1±9.0 in the treatment group compared to 1.0 points from a baseline of 37.6±7.9 in the placebo group (F=4.514, P=0.018). After adjusting for baseline differences, significant improvement was observed in mental health composite scores, but not in physical health composite scores. Long-acting testosterone undecanoate significantly improved the mental health component of QoL in men with TDS. PMID:22635164

  16. Suppression of spermatogenesis by testosterone undecanoate-loaded injectable in situ-forming implants in adult male rats.

    PubMed

    Zhang, Xiao-Wei; Zhang, Chong; Zhang, Wei; Yang, Dan; Meng, Shu; Wang, Ping; Guo, Jing; Liu, Dan-Hua

    2016-01-01

    We have investigated the feasibility of administration of testosterone undecanoate (TU)-loaded injectable in situ-forming implant (ISFI) for contraception in adult male Sprague-Dawley rats. Male rats were treated with vehicle, TU-loaded ISFIs (540, 270 and 135 mg TU kg-1 ) or TU injections (45 mg TU kg-1 every 30 days) for 120 days. Fertility tests served for determining infertility or restoration of fertility in treated rats. Serum testosterone concentration, epididymal sperm count, motility, morphology, and histology of the testis were monitored. The TU-loaded ISFIs increased serum testosterone levels in rats steadily without fluctuation over 3 months. One month after TU administration, the epididymal sperm count decreased significantly in all experimental groups. After 3 months, the animals treated with 270 and 135 mg kg-1 TU-loaded ISFIs were 100% infertile, and no implantation sites were produced in the mated females. However, some of males treated with 540 mg kg-1 ISFI or TU injections were still fertile but numbers of implantation sites were also significantly lower than control values. TU-loaded ISFI at an appropriate dose has potential as a long-acting male contraceptive drug that suppresses spermatogenesis consistently over a period of 3 months.

  17. Genetic polymorphisms of CYP2D6*10 and the effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in infertile men with idiopathic oligozoospermia.

    PubMed

    Tang, Kai-fa; Zhao, Yi-li; Ding, Shang-shu; Wu, Qi-fei; Wang, Xing-yang; Shi, Jia-qi; Sun, Fa; Xing, Jun-ping

    2015-03-01

    Tamoxifen citrate, as the first line of treatment for infertile men with idiopathic oligozoospermia, was proposed by the World Health Organization (WHO), and testosterone undecanoate has shown benefits in semen values. Our objective was to assess the effectiveness of treatment with tamoxifen citrate and testosterone undecanoate in infertile men with idiopathic oligozoospermia, and whether the results would be affected by polymorphisms of CYP2D6*10. A total of 230 infertile men and 147 controls were included in the study. Patients were treated with tamoxifen citrate and testosterone undecanoate. Sex hormone, sperm parameters, and incidence of spontaneous pregnancy were detected. There were no significant differences between the control and patient groups with respect to CYP2D6*10 genotype frequencies (P>0.05). The follicle-stimulation hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were raised, and sperm concentration and motility were increased at 3 months and became significant at 6 months, and they were higher in the wild-type allele (C/C) than in the heterozygous variant allele (C/T) or homozygous variant allele (T/T) subgroups (P<0.05). In addition, the percentage of normal morphology was raised at 6 months, and represented the highest percentage in the C/C subgroup (P<0.05). The incidence of spontaneous pregnancy in the C/C subgroup was higher than that in the C/T or T/T subgroups (P<0.01). This study showed that the CYP2D6*10 variant genotype demonstrated worse clinical effects in infertile men with idiopathic oligozoospermia.

  18. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes.

    PubMed

    Hackett, Geoffrey; Cole, Nigel; Bhartia, Mithun; Kennedy, David; Raju, Jessie; Wilkinson, Peter

    2013-06-01

    Sexual dysfunction, particularly erectile dysfunction (ED), is common in men with type 2 diabetes, occurring in up to 75% of cases. The prevalence of hypogonadism is also high in men with diabetes and low testosterone is associated with both sexual dysfunction and a reduced response to oral therapy for ED. This study aimed to determine the effect of testosterone replacement with long-acting Testosterone Undecanoate (TU) on sexual function, mood and quality of life vs. placebo over a treatment period of 30 weeks followed by 52 weeks of open-label medication. The study was conducted in a primary care population of men with type 2 diabetes attending their primary care physician for routine visits. The male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L or less. Two hundred eleven men were screened. A double-blind placebo-controlled study was conducted in 199 men with type 2 diabetes and hypogonadism treated for 30 weeks with either 1,000 mg of TU or matching placebo followed by 52-week open-label follow on. The primary outcome measure, International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression Scale, and Global Efficacy Question were used as secondary outcome measures to assess mood and self-reported quality of life. Testosterone replacement therapy with long-acting TU improved all domains of sexual function at 30 weeks (erectile function [EF], P = 0.005; intercourse satisfaction, P = 0.015; sexual desire, P = 0.001; overall satisfaction, P = 0.05; and orgasm, P = 0.04), with benefit as early as 6 weeks. Improvements in AMS score were significant in men without depression (P = 0.02) and the presence of depression at baseline was associated with marked reduction in response to both sexual function and psychological

  19. Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

    PubMed

    Ayoub, R; Page, S T; Swerdloff, R S; Liu, P Y; Amory, J K; Leung, A; Hull, L; Blithe, D; Christy, A; Chao, J H; Bremner, W J; Wang, C

    2017-03-01

    Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be

  20. Development of dimethandrolone 17beta-undecanoate (DMAU) as an oral male hormonal contraceptive: induction of infertility and recovery of fertility in adult male rabbits.

    PubMed

    Attardi, Barbara J; Engbring, Jean A; Gropp, David; Hild, Sheri Ann

    2011-01-01

    Dimethandrolone undecanoate (DMAU: 7α,11β-dimethyl-19-nortestosterone 17β-undecanoate) is a potent orally active androgen with progestational activity that is in development for therapeutic uses in men. We hypothesized that because of its dual activity, DMAU might have potential as a single-agent oral hormonal contraceptive. To test this possibility, adult male rabbits (5/group) of proven fertility were treated orally with vehicle or DMAU at 1.0, 2.5, 5.0, or 10.0 mg/kg/d for 12 or 13 weeks. Semen and blood samples were collected every other week through week 30. Sperm were decreased (P < .05) in semen samples from DMAU-treated rabbits at 2.5 and 5.0 mg/kg/d at weeks 12, 14, 16, 18, and 20 compared to week 0 (prior to treatment). The percentage of forward progressive motile sperm in those rabbits that still had measurable sperm was also reduced by DMAU treatment at 2.5 mg/kg/d at weeks 14, 16, 18, and 20 and at 5.0 mg/kg/d at week 18 (P < .05). At 1.0 mg/kg/d only 1 rabbit had reduced sperm numbers and motility. A mating trial was performed at week 15. The number of bred males that were fertile was 4 of 4 in the vehicle-treated group and 4 of 5, 0 of 4, and 2 of 5 in the 1.0, 2.5, and 5.0 mg/kg/d DMAU treatment groups. By week 22, sperm numbers and forward progressive motility increased, and they returned to pretreatment levels in all DMAU-treated rabbits by week 30. All bred males were fertile at week 31. Serum levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were significantly suppressed in DMAU (1.0, 2.5, or 5.0 mg/kg/d)-treated rabbits during the 12-week dosing interval, but were comparable to pretreatment levels after cessation of dosing. These data indicate that DMAU suppressed the hypothalamic-pituitary-gonadal axis, resulting in severe oligospermia in the majority of rabbits in the 2.5 and 5.0 mg/kg/d dosing groups. Infertility was observed when sperm numbers decreased to about 10% of pretreatment levels. In

  1. Complete sperm suppression induced by dienogest plus testosterone undecanoate is associated with down-regulation in the expression of upstream steroidogenic enzyme genes in rat testis.

    PubMed

    Meena, Rekha; Misro, Man Mohan; Ghosh, Debidas; Nandan, Deoki

    2012-08-01

    We had shown that dienogest (DNG) + testosterone undecanoate (TU) induced complete sperm suppression in rats when administered together every 45 days. On the other hand, individual drugs given alone in a similar fashion failed to achieve the same result. The present study was therefore undertaken to determine the reason for such a differential sperm suppression and to correlate it with the expression of steroidogenic enzyme genes in the rat testis. Administration of DNG (40 mg/kg body weight [bw]) + TU (25 mg/kg bw) every 45 days for a duration of 90 days induced spermatogenic arrest, leading to a significant reduction in testicular weight and number of precursor germ cells. Flow cytometric analysis further confirmed the same result, leading to a significant shift in the distribution of haploid cells. Measurement of testosterone (serum and intratesticular) was significantly low. Complete sperm suppression coincided with significant down-regulation in the expression of upstream steroidogenic enzyme genes represented serially by cytochrome P450 side-chain cleavage, P450 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein (StAR) in the testis. On the other hand, rats administered with either DNG or TU alone demonstrated incomplete sperm suppression in which the expression of all the above genes remained characteristically nonuniform. Taken together, the above findings corroborate the fact that regulation of expression of three of the upstream steroidogenic enzymes genes and the StAR protein in rat testis is crucial in leading to complete sperm suppression as observed with DNG+TU treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Testosterone undecanoate improves sexual function in men with type 2 diabetes and severe hypogonadism: results from a 30-week randomized placebo-controlled study.

    PubMed

    Hackett, Geoffrey; Cole, Nigel; Saghir, Atif; Jones, Peter; Strange, Richards C; Ramachandran, Sudarshan

    2016-11-01

    To evaluate the sexual function response to 30 weeks' treatment with long-acting testosterone undecanoate (TU) or placebo in 199 men with type 2 diabetes and either severe or mild hypogonadism (HG). Men with HG were identified from seven primary care type 2 diabetes registers. A 30-week randomized placebo-controlled study of TU was carried out in 199 of these men (placebo, n = 107, TU, n = 92). The patient-reported outcome measure was the 15-item International Index of Erectile Function score. Men completing the study (n=189) were stratified, firstly, by baseline total testosterone (TT) or free testosterone (FT) into mild HG (TT 8.1-12 nmol/L or FT 0.18-0.25 nmol/L) and severe HG groups (TT ≤8 nmol/L and FT ≤0.18 nmol/L), and secondly, by intervention (placebo or TU), thereby creating four groups: mild HG/placebo; mild HG/TU; severe HG/placebo and severe HG/TU. Changes in sexual function score (a secondary outcome of the study) at each visit within group (from baseline) and between groups (TU vs placebo) at each assessment (6, 18 and 30 weeks) were compared using a Wilcoxon signed-rank and Wilcoxon rank-sum test, respectively. Significant improvement in erectile function was evident only in the severe HG group after 30 weeks of TU treatment; this finding persisted when TU was compared with placebo. Intercourse satisfaction and sexual desire scores were also improved at 6, 18 and 30 weeks in the severe HG group after TU treatment; this increase in scores was also evident when compared with placebo. TU did not appear to alter orgasmic function significantly in any of the patient groups. The present study suggests that benefit in sexual symptoms after TU treatment is evident principally in patients with HG with TT levels ≤8 nmol/L and FT levels ≤0.18 nmol/L. We also suggest that 30 weeks of treatment is necessary before evaluating improvement in erectile function. © 2016 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU

  3. The effect of food composition on serum testosterone levels after oral administration of Andriol® Testocaps®

    PubMed Central

    Schnabel, Peter G; Bagchus, Wilma; Lass, Holger; Thomsen, Torben; Geurts, T B Paul

    2007-01-01

    Objective Andriol® Testocaps® is a new oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. The aim of this study was to investigate the effect of food composition on the pharmacokinetics of oral TU. Design An open-label, single-centre, four-way crossover study. With a washout period of 6–7 days, 80 mg TU was administered in the morning 5 min after consuming each of four different meals in a randomized order (A: 230 kcal, 0·6 g lipid; B: 220 kcal, 5 g lipid; C: 474 kcal, 19 g lipid; D: 837 kcal, 44 g lipid). Patients Twenty-four postmenopausal volunteers. Measurements Serial blood samples were collected until 24 h after dosing to determine testosterone and dihydrotestosterone (DHT) by gas chromatography-mass spectroscopy (GC-MS). Results The bioavailability of testosterone after a low-calorie meal containing 0·6 g lipid or 5 g lipid was relatively low, the area under the concentration–time curve (AUC0–tlast) for testosterone being 30·7 and 43·5 nmol h/l, respectively. The bioavailability of testosterone after a meal containing 19 g lipid was considerably higher (AUC0–tlast = 146 nmol h/l), whereas increasing the lipid content to 44 g lipid did not further increase the bioavailability of testosterone (AUC0–tlast = 154 nmol h/l). Conclusion Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU. PMID:17371478

  4. Single, Escalating Dose Pharmacokinetics, Safety and Food Effects of a New Oral Androgen Dimethandrolone Undecanoate in Man: A prototype oral male hormonal contraceptive

    PubMed Central

    Swerdloff, Ronald S.; Nya-Ngatchou, Jean Jacques; Liu, Peter Y.; Amory, John K.; Leung, Andrew; Hull, Laura; Blithe, Diana L.; Woo, Jason; Bremner, William J.; Wang, Christina

    2014-01-01

    The novel androgen, dimethandrolone (DMA) has both androgenic and progestational activities, properties that may maximize gonadotropin suppression. We assessed the pharmacokinetics of dimethandrolone undecanoate (DMAU), an orally bioavailable, longer-acting ester of DMA, for male contraceptive development. Our objective was to examine the safety and pharmacokinetics of single, escalating doses of DMAU (powder in capsule formulation) administered orally with or without food in healthy men. We conducted a randomized, double-blind Phase 1 study. For each dose of DMAU (25 to 800 mg), ten male volunteers received DMAU and two received placebo at two academic medical centers. DMAU was administered both fasting and after a high fat meal (200–800 mg doses). Serial serum samples were collected over 24h following each dose. DMAU was well tolerated without significant effects on vital signs, safety laboratory tests or electrocardiograms. When administered while fasting, serum DMA (active compound) was detectable in only 4/10 participants after the 800mg dose. When administered with a 50% fat meal, serum DMA was detectable in all participants given 200mg DMAU and showed a dose-incremental increase up to 800mg, with peak levels 4 to 8h after taking the dose. Serum gonadotropins and sex hormone concentrations were significantly suppressed 12h after DMAU administration with food at doses above 200mg. This first-in-man study demonstrated that a single, oral dose of DMAU up to 800 mg is safe. A high-fat meal markedly improved DMAU/DMA pharmacokinetics. PMID:24789057

  5. Urinary analysis of four testosterone metabolites and pregnanediol by gas chromatography-combustion-isotope ratio mass spectrometry after oral administrations of testosterone.

    PubMed

    Maître, Arnaud; Saudan, Christophe; Mangin, Patrice; Saugy, Martial

    2004-09-01

    The most frequently used method to demonstrate testosterone abuse is the determination of the testosterone and epitestosterone concentration ratio (T/E ratio) in urine. Nevertheless, it is known that factors other than testosterone administration may increase the T/E ratio. In the last years, the determination of the carbon isotope ratio has proven to be the most promising method to help discriminate between naturally elevated T/E ratios and those reflecting T use. In this paper, an excretion study following oral administration of 40 mg testosterone undecanoate initially and 13 h later is presented. Four testosterone metabolites (androsterone, etiocholanolone, 5 alpha-androstanediol, and 5 beta-androstanediol) together with an endogenous reference (5 beta-pregnanediol) were extracted from the urines and the delta(13)C/(12)C ratio of each compound was analyzed by gas chromatography-combustion-isotope ratio mass spectrometry. The results show similar maximum delta(13)C-value variations (parts per thousand difference of delta(13)C/(12)C ratio from the isotope ratio standard) for the T metabolites and concomitant changes of the T/E ratios after administration of the first and the second dose of T. Whereas the T/E ratios as well as the androsterone, etiocholanolone and 5 alpha-androstanediol delta(13)C-values returned to the baseline 15 h after the second T administration, a decrease of the 5 beta-androstanediol delta-values could be detected for over 40 h. This suggests that measurements of 5 beta-androstanediol delta-values allow the detection of a testosterone ingestion over a longer post-administration period than other T metabolites delta(13)C-values or than the usual T/E ratio approach.

  6. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

    PubMed

    Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

    2014-04-01

    Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body

  7. The Effect of Testosterone and Fenofibrate, Administered Alone or in Combination, on Cardiometabolic Risk Factors in Men with Late-Onset Hypogonadism and Atherogenic Dyslipidemia.

    PubMed

    Krysiak, Robert; Gilowski, Wojciech; Okopien, Bogusław

    2015-10-01

    Oral testosterone was found to reduce plasma levels of HDL cholesterol. No previous study has examined the effect of fibrates, known to increase HDL cholesterol, in patients with low testosterone levels requiring testosterone replacement. The study included three age-, weight-, and lipid-matched groups of older men with atherogenic dyslipidemia and late-onset hypogonadism, treated with oral testosterone undecanoate (120 mg daily, n = 15), micronized fenofibrate (200 mg daily, n = 15), or testosterone plus fenofibrate (n = 18). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 16 weeks of therapy. Apart from an increase in plasma testosterone and a reduction in HDL cholesterol, testosterone undecanoate tended to decrease hsCRP and to improve insulin sensitivity. Fenofibrate administered alone increased HDL cholesterol, reduced triglycerides, decreased insulin resistance, reduced circulating levels of uric acid, hsCRP, and fibrinogen, as well as increased plasma levels of homocysteine. The strongest effect on testosterone, HOMA1-IR, uric acid, hsCRP, and fibrinogen was observed if fenofibrate was administered together with testosterone. Testosterone-fenofibrate combination therapy was also devoid of unfavorable effect on HDL cholesterol and homocysteine. Our study shows that fenofibrate produces a stronger effect on cardiometabolic risk factors in men with late-onset hypogonadism and atherogenic dyslipidemia than oral testosterone undecanoate. The obtained results suggest that this group of patients may benefit the most from the combined treatment with oral testosterone undecanoate and micronized fenofibrate. © 2015 John Wiley & Sons Ltd.

  8. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement.

    PubMed

    Kim, Edward D; McCullough, Andrew; Kaminetsky, Jed

    2016-04-01

    To determine the effects of daily oral doses of enclomiphene citrate compared with topical testosterone gel treatment on serum total testosterone (TT), luteinising hormone (LH), follicle-stimulating hormone (FSH), and sperm counts in men with secondary hypogonadism. Two parallel randomised, double-blind, double-dummy, placebo-controlled, multicentre, phase III studies were undertaken to evaluate two doses of enclomiphene citrate vs testosterone gel (AndroGel(®) 1.62%) on TT, LH, FSH, and sperm counts in overweight men aged 18-60 years with secondary hypogonadism. Men were screened and enrolled in the trials (ZA-304 and ZA-305). All enrolled men had early morning serum TT levels in the low or low normal range (≤300 ng/dL; ≤10.4 nmol/L) and had low or normal LH (<9.4 IU/L) levels measured on two separate occasions 2-10 days apart. Serum samples were obtained over the course of the study to determine relevant hormone levels at baseline and after 16 weeks of treatment. Men provided semen samples twice to enroll at the beginning and twice at the end of the study. TT levels increased between baseline and after 16 weeks of treatment in all the treatment groups. FSH and LH levels increased in the enclomiphene citrate groups and decreased in the testosterone gel group at 16 weeks. Enclomiphene citrate maintained sperm concentration in the normal range over the treatment period, while there was a marked reduction in spermatogenesis in the testosterone gel group. Enclomiphene citrate consistently increased serum TT, LH and FSH, restoring normal levels of serum TT. Enclomiphene citrate treatment maintained sperm concentrations in the normal range. The effects on TT were also seen with testosterone replacement via testosterone gel but sperm counts were not maintained. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  9. Peculiar observations in measuring testosterone in women treated with oral contraceptives supplemented with dehydroepiandrosterone (DHEA).

    PubMed

    Heijboer, Annemieke C; Zimmerman, Yvette; de Boer, Theo; Coelingh Bennink, Herjan; Blankenstein, Marinus A

    2014-03-20

    Total testosterone is considered to be decreased during the use of combined oral contraceptives. There is, however, considerable concern about the quality of testosterone assays, especially at low levels. We aimed to confirm testosterone levels measured by direct radioimmunoassay in a recent clinical trial with a state-of-the-art LC-MSMS method. Surplus specimens with known testosterone levels collected during the study (Clinical Trial Registration number ISRCTN06414473) were reanalyzed with an LC-MSMS method. This method was compared to another LC-MSMS method that had shown to concur excellently to a reference method. Follow-up experiments were designed to explain the results. In contrast to our expectation, LC-MSMS measurements did not corroborate the data obtained by radioimmunoassay. Subsequent experiments showed that this could be attributed to a strong dependency of the radioimmunoassay on SHBG. Testosterone results (n = 198) obtained by direct radioimmunoassay showed a negative correlation to SHBG levels (r = -0.676; p<0.001). By contrast, testosterone results obtained by LC-MSMS were not related to SHBG (r = 0.100; NS). In conclusion, our results indicate that total testosterone measurements during oral contraceptive use are unreliable when performed with assays sensitive to the SHBG concentration. The discrepancy with the literature can most likely be explained by the sensitivity of the immunoassay used to SHBG. Given the sharp increase in SHBG during the use of many oral contraceptives, total testosterone may not decrease, whereas its bioavailability, estimated by free testosterone levels, will be diminished. Studies aiming at restoration of testosterone homeostasis during oral contraception need to take this into account. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males' Symptoms rating scale (AMS) questionnaires.

    PubMed

    Emmelot-Vonk, M H; Verhaar, H J J; Nakhai-Pour, H R; Grobbee, D E; van der Schouw, Y T

    2011-04-01

    First, to assess the association between the concentration of serum testosterone and the symptoms of testosterone deficiency according to two screening questionnaires. Second, to investigate the effects in elderly men with a low-normal testosterone concentration of testosterone supplementation over a period of 6 months on symptoms of testosterone deficiency according to the screening questionnaires. A total of 587 men between 60 and 80 years of age with an eligible serum testosterone measurement and completion of the screening questionnaires were included in the study. Of these 587 men, 237 men with testosterone levels <13·7 nmol/l were included in a double-blind, randomized, placebo-controlled trial of testosterone supplementation. One hundred and sixty milligrams per day of oral testosterone undecanoate or a matching placebo for 6 months. The Androgen Deficiency in Ageing Males (ADAM) and the Ageing Males' Symptoms rating scale (AMS) questionnaires. There was no significant association between the total testosterone concentration and the scores on the two questionnaires. However, age was significantly associated with the scores on the ADAM (OR 1·14, 95% CI 1·05-1·23) and the AMS (OR 1·03, 95% CI 1·01-1·08) questionnaire. After supplementation with testosterone, there were no effects on the scores on the two questionnaires in the testosterone group compared with the placebo group. The findings do not support the use of the ADAM or AMS questionnaire in the evaluation of late-onset hypogonadism in ageing men. Moreover, 6 months of oral testosterone supplementation had no significant effect on scores of the ADAM and AMS questionnaire in this group of elderly men with low-normal testosterone levels. © 2011 Blackwell Publishing Ltd.

  11. Testosterone deficiency: a historical perspective.

    PubMed

    Nieschlag, Eberhard; Nieschlag, Susan

    2014-01-01

    Castillo and Pasqualini. In the 1950s longer-acting injectable testosterone enanthate became the preferred therapeutic modality. In the 1950s and 1960s, research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. Although anabolic steroids have largely disappeared from clinical medicine, they continue to live an illegal life for doping in athletics. In the 1970s the orally effective testosterone undecanoate was added to the spectrum of preparations. Recent transdermal gels and long-acting injectable preparations provide options for physiological testosterone substitution therapy.

  12. Testosterone deficiency: a historical perspective

    PubMed Central

    Nieschlag, Eberhard; Nieschlag, Susan

    2014-01-01

    Castillo and Pasqualini. In the 1950s longer-acting injectable testosterone enanthate became the preferred therapeutic modality. In the 1950s and 1960s, research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. Although anabolic steroids have largely disappeared from clinical medicine, they continue to live an illegal life for doping in athletics. In the 1970s the orally effective testosterone undecanoate was added to the spectrum of preparations. Recent transdermal gels and long-acting injectable preparations provide options for physiological testosterone substitution therapy. PMID:24435052

  13. Recent trends in the treatment of testosterone deficiency syndrome.

    PubMed

    Hong, Bum Sik; Ahn, Tai Young

    2007-11-01

    Testosterone deficiency syndrome (TDS) is defined as a clinical and biochemical syndrome associated with advancing age and is characterized by typical symptoms and deficiency in serum testosterone levels. TDS is a result of the interaction of hypothalamo-pituitary and testicular factors. Now, treatment of TDS with testosterone is still controversial due to a lack of large, controlled clinical trials on efficacy. The risks of treatment with testosterone appear to be minimal, although long-term studies on the safety of testosterone therapy are lacking. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Newer testosterone patches seem not to cause severe skin irritation. Testosterone gels minimize the skin irritation while providing flexibility in dosing and a low discontinuation rate. Oral testosterone undecanoate (TU) is free of liver toxicity. Recent formulation of oral TU markedly increased shelf-live, a major drawback in the older preparation. Producing swings in testosterone levels rising rapidly to the supraphysiological range is not the case with the new injectable long-acting preparation of TU. To be able to rapidly react and stop treatment in cases where side-effects and contraindications are detected, the short-acting transdermal and oral delivery modes have certain advantages. However, there is no evidence that the use of an injectable long-acting TU in men with TDS has limitations in clinical application for this reason. The use of dehydroepiandrosterone is still controversial because of a lack of well designed long-term trials, although some recent studies suggest positive effects on various body systems. Only a few studies have been carried out to investigate the effect of hCG (human

  14. Oral testosterone in male rats and the development of experimental autoimmune encephalomyelitis.

    PubMed

    Macció, Daniela R; Calfa, Gastón; Roth, German A

    2005-01-01

    Considering that sex steroids can influence the immune system, we studied the development of experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of the central nervous system, and the concomitant cell-mediated immunity in gonadally intact and gonadectomized male Wistar rats given testosterone supplementation. Sham-operated rats and surgically castrated animals were orally self-administered with vehicle or testosterone added in the water bottle for 20 days before EAE induction. The androgenic effect of oral testosterone self-administration was evidenced by changes in body weight, and in the weights of androgen-dependent testes and seminal vesicles. Testosterone administration reduced the incidence of clinical signs of EAE in sham-operated animals and reversed the clinical symptoms of the disease associated with castrated EAE animals. The clinical signs observed in the different groups correlated with changes in delayed-type hypersensitivity and mononuclear cell-proliferative responses to the encephalitogenic myelin basic protein. Moreover, testosterone but not cholesterol supplementation in vitro suppressed the proliferative response of mononuclear cells to myelin basic protein suggesting that testosterone may affect specific immune functions through direct actions on immune cells. Finally, self-administration of testosterone induced also elevated corticosterone levels that in sham-operated rats correlated with the low incidence of the disease and in gonadectomized animals could be involved in the remission of clinical symptoms of EAE. These results suggest that orally self-administered testosterone can modulate specific cellular immune responses and serum corticosterone levels leading to changes in the development of EAE. Copyright 2005 S. Karger AG, Basel.

  15. The risk of adverse outcomes in association with use of testosterone products: a cohort study using the UK-based general practice research database

    PubMed Central

    Jick, Susan S; Hagberg, Katrina Wilcox

    2013-01-01

    AIMS To study the relative safety of the intramuscular injection formulation of testosterone with oral testosterone undecanoate in relation to the risks for hypertension, polycythemia, prostate cancer, benign prostatic hypertrophy (BPH) and prostatism. METHODS We conducted a cohort study of men in the UK based General Practice Research Database who were users of the oral undecanoate and injectable forms of testosterone and calculated rates and relative risks of hypertension, polycythemia and prostate conditions (cancer, BPH and prostatism). RESULTS We identified 5841 men who received at least one study testosterone preparation. There were 202 cases of hypertension (crude incidence rates (IRs) for oral and injectable testosterone respectively 12.3/1000 person-years (PY) and 14.4/1000 PY). There were 146 cases of polycythemia (IRs 1.2/1000 PY and 10.1/1000 PY), 46 cases of prostate cancer (IRs 2.5/1000 PY and 1.8/1000 PY), 106 cases of BPH (IRs 4.1 /1000 PY and 2.1/1000 PY), and 251 cases of prostatism (IRs 8.4/1000 PY and 6.1/1000 PY respectively). Adjusted relative risks for oral compared with injectable testosterone were 0.8 (95% CI 0.6, 1.2) for hypertension, 0.13 (0.05, 0.35) for polycythemia, 1.1 (0.7, 1.7) for prostate cancer, 1.5 (1.1, 2.2) for BPH and 1.1 (0.8, 1.4) for prostatism. CONCLUSIONS Risks of prostate cancer and prostatism were similar in users of the two preparations, but risks were higher for hypertension and polycythemia in the injectable compared with the oral testosterone users. Risk of BPH was slightly higher in the oral users, but the difference was small and could have been due to bias. PMID:22574772

  16. Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

    PubMed

    Badoud, F; Boccard, J; Schweizer, C; Pralong, F; Saugy, M; Baume, N

    2013-11-01

    The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the

  17. Pharmacokinetics of 2 Novel Formulations of Modified-Release Oral Testosterone Alone and With Finasteride in Normal Men With Experimental Hypogonadism

    PubMed Central

    Snyder, Christin N.; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Roth, Mara Y.; Page, Stephanie T.; Bremner, William J.; Amory, John K.

    2011-01-01

    Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current “immediate-release” formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiologic peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed 2 novel modified-release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in 16 normal young men enrolled in a 2-arm, open-label clinical trial. Three hundred-mg and 600-mg doses of immediate-release and modified fast-release or slow-release formulations were administered sequentially to 8 normal men rendered hypogonadal by the administration of the gonadotropin-releasing hormone antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of 8 men was studied with the coadministration of 1 mg of the 5α-reductase inhibitor finasteride daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the postdose peaks of serum testosterone and reduced peak concentrations of serum DHT compared with the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared with immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency. PMID:20378927

  18. Pharmacokinetics and Pharmacodynamics of Oral Testosterone Enanthate Plus Dutasteride for 4 Weeks in Normal Men: Implications for Male Hormonal Contraception

    PubMed Central

    AMORY, JOHN K.; KALHORN, THOMAS F.; PAGE, STEPHANIE T.

    2009-01-01

    Oral administration of testosterone enanthate (TE) and dutasteride increases serum testosterone and might be useful for male hormonal contraception. To ascertain the contraceptive potential of oral TE and dutasteride by determining the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400 mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded, controlled fashion at a single site. All men received 0.5 mg dutasteride daily. Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours after the morning dose on the last day of treatment. FSH was significantly suppressed throughout treatment with 800 mg TE once daily and after 4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was suppressed and serum estradiol increased during treatment in both groups. High-density lipoprotein cholesterol was suppresed during treatment, but liver function tests, hematocrit, creatinine, mood, and sexual function were unaffected. The administration of 800 mg oral TE daily combined with dutasteride for 28 days significantly suppresses gonadotropins without untoward side effects and might have utility as part of a male hormonal contraceptive regimen. PMID:18046048

  19. Pharmacokinetics and pharmacodynamics of oral testosterone enanthate plus dutasteride for 4 weeks in normal men: implications for male hormonal contraception.

    PubMed

    Amory, John K; Kalhorn, Thomas F; Page, Stephanie T

    2008-01-01

    Oral administration of testosterone enanthate (TE) and dutasteride increases serum testosterone and might be useful for male hormonal contraception. To ascertain the contraceptive potential of oral TE and dutasteride by determining the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400 mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded, controlled fashion at a single site. All men received 0.5 mg dutasteride daily. Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours after the morning dose on the last day of treatment. FSH was significantly suppressed throughout treatment with 800 mg TE once daily and after 4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was suppressed and serum estradiol increased during treatment in both groups. High-density lipoprotein cholesterol was suppresed during treatment, but liver function tests, hematocrit, creatinine, mood, and sexual function were unaffected. The administration of 800 mg oral TE daily combined with dutasteride for 28 days significantly suppresses gonadotropins without untoward side effects and might have utility as part of a male hormonal contraceptive regimen.

  20. A pilot study on subject-based comprehensive steroid profiling: novel biomarkers to detect testosterone misuse in sports.

    PubMed

    Van Renterghem, Pieter; Van Eenoo, Peter; Sottas, Pierre-Edouard; Saugy, Martial; Delbeke, Frans

    2011-07-01

    Until now, the testosterone/epitestosterone (T/E) ratio is the main marker for the detection of testosterone (T) misuse in athletes. As this marker can be influenced by a number of confounding factors, additional steroid profile parameters indicating T misuse can provide substantiating evidence of doping with endogenous steroids. The evaluation of a steroid profile is currently based upon population statistics. As large inter-individual variations exist, a paradigm shift towards subject-based references is ongoing in doping analysis. Proposition of new biomarkers for the detection of testosterone in sports using extensive steroid profiling and an adaptive model based upon Bayesian inference. Six healthy male volunteers were administered with testosterone undecanoate. Population statistics were performed upon steroid profiles from 2014 male Caucasian athletes participating in official sport competition. An extended search for new biomarkers in a comprehensive steroid profile combined with Bayesian inference techniques as used in the athlete biological passport resulted in a selection of additional biomarkers that may improve detection of testosterone misuse in sports. Apart from T/E, 4 other steroid ratios (6α-OH-androstenedione/16α-OH-dehydroepiandrostenedione, 4-OH-androstenedione/16α-OH-androstenedione, 7α-OH-testosterone/7β-OH-dehydro-epiandrostenedione and dihydrotestosterone/5β-androstane-3α,17β-diol) were identified as sensitive urinary biomarkers for T misuse. These new biomarkers were rated according to relative response, parameter stability, detection time and discriminative power. Newly selected biomarkers were found suitable for individual referencing within the concept of the Athlete's Biological Passport. The parameters showed improved detection time and discriminative power compared to the T/E ratio. Such biomarkers can support the evidence of doping with small oral doses of testosterone. © 2011 Blackwell Publishing Ltd.

  1. Could Testosterone Replacement Therapy in Hypogonadal Men Ameliorate Anemia, a Cardiovascular Risk Factor? An Observational, 54-Week Cumulative Registry Study.

    PubMed

    Zhang, Li Tao; Shin, Yu Seob; Kim, Ji Yong; Park, Jong Kwan

    2016-04-01

    In this study we investigated if testosterone undecanoate attenuates anemia and the risk of cardiovascular disease in patients with hypogonadism. A registry study consisted of 58 participants with a subnormal total testosterone level (less than 2.35 ng/ml) and at least mild symptoms of testosterone deficiency. All patients received an injection of 1,000 mg testosterone undecanoate at the initial visit, followed by injection at 6, 18, 30, 42 and 54 weeks. Serum hormones, hemoglobin, hematocrit, anemia risk factors, lipid profiles, whole blood viscosity and anthropometry were measured. Total testosterone (from mean ± SD 1.87 ± 1.09 to 5.52 ± 1.92 ng/ml, p <0.001) and free testosterone (from 3.04 ± 2.03 to 7.23 ± 2.90 pg/ml, p <0.001) were restored by testosterone undecanoate therapy. Hemoglobin and hematocrit significantly increased after testosterone undecanoate therapy by an average of 2.46 gm/dl (p <0.001) and 3.03% (p <0.001), respectively. The prevalence of anemia (from 29.6% to 10.0%) significantly decreased (p <0.001) and patients with anemia showed a significant increase in erythropoietin after testosterone undecanoate therapy (p = 0.047). A reduction in total cholesterol (from 165.89 ± 39.16 to 153.80 ± 154.27 mg/dl, p = 0.002), increased whole blood viscosity and increased hematocrit were observed until 54 weeks compared with baseline. However, whole blood viscosity and hematocrit stabilized after 18 weeks. After 54 weeks testosterone undecanoate decreased the prevalence of anemia and components of the metabolic syndrome. A longer duration of testosterone undecanoate therapy of more than 18 weeks may be effective and safe in reducing blood viscosity and improving anemia. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Testosterone treatment of hypogonadal men participating in competitive sports.

    PubMed

    Gooren, L J; Behre, H M

    2008-06-01

    Testosterone has a steeply dose-dependent effect on muscle mass and strength irrespective of gonadal status. So, for reasons of fairness, people who engage in competitive sports should not administer exogenous testosterone raising their blood testosterone levels beyond the range of normal. There is a ban on exogenous androgens for men and women in sports, but an exception has been made for men with androgen deficiency due to pituitary or testicular disease. Men who receive testosterone administration for the indication hypogonadism have an interest in the use of testosterone preparations generating blood testosterone levels within the normal range of healthy, eugonadal men. On the grounds of a positive correlation between blood testosterone concentrations muscle and volume/strength, they are best served with a parenteral testosterone preparation, rather than transdermal testosterone, but they should not run the risk of being excluded from competition because of supraphysiological testosterone levels. The latter is a realistic risk with the traditional parenteral testosterone esters. The new parenteral testosterone undecanoate preparation offers much better perspectives. Its pharmacokinetics have been investigated in detail and there is a fair degree of predictability of resulting blood testosterone levels with use of this preparation.

  3. Detection of testosterone esters in blood.

    PubMed

    Forsdahl, Guro; Erceg, Damir; Geisendorfer, Thomas; Turkalj, Mirjana; Plavec, Davor; Thevis, Mario; Tretzel, Laura; Gmeiner, Günter

    2015-01-01

    Injections of synthetic esters of testosterone are among the most common forms of testosterone application. In doping control, the detection of an intact ester of testosterone in blood gives unequivocal proof of the administration of exogenous testosterone. The aim of the current project was to investigate the detection window for injected testosterone esters as a mixed substance preparation and as a single substance preparation in serum and plasma. Furthermore, the suitability of different types of blood collection devices was evaluated. Collection tubes with stabilizing additives, as well as non-stabilized serum separation tubes, were tested. A clinical study with six participants was carried out, comprising a single intramuscular injection of either 1000 mg testosterone undecanoate (Nebido(®)) or a mixture of 30 mg testosterone propionate, 60 mg testosterone phenylpropionate, 60 mg testosterone isocaproate, and 100 mg testosterone decanoate (Sustanon(®)). Blood was collected throughout a testing period of 60 days. The applied analytical method for blood analysis included liquid-liquid extraction and preparation of oxime derivatives, prior to TLX-sample clean-up and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection. All investigated testosterone esters could be detected in post-administration blood samples. The detection time depended on the type of ester administered. Furthermore, results from the study show that measured blood concentrations of especially short-chained testosterone esters are influenced by the type of blood collection device applied. The testosterone ester detection window, however, was comparable. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Does oral contraceptive-induced reduction in free testosterone adversely affect the sexuality or mood of women?

    PubMed

    Graham, Cynthia A; Bancroft, John; Doll, Helen A; Greco, Theresa; Tanner, Amanda

    2007-04-01

    The aim of this study was to examine whether changes in plasma androgen levels (total testosterone (T), free testosterone (FT), and dehydro-epiandrosterone-sulfate (DHEA-S)) induced by oral contraceptive (OC) use were related to changes in sexual interest or response or in mood. Sixty-one women provided blood samples and were assessed, using interviews and standardized questionnaires, prior to starting, and after 3 months on OCs (Ortho-Tricyclen, Ortho-Tricyclen-Lo, or Ortho-Cyclen, all containing the same progestagen, norgestimate). Significant decreases in T, FT, and DHEA-S were found after 3 months, although the extent of reduction was variable across women. There was some support for a relationship between the degree of reduction in total T and FT and the frequency of sexual thoughts after 3 months on OCs. However, some women had no loss of sexual interest in spite of substantial reduction in FT, and there was overall no evidence that reduction in FT affected enjoyment of sexual activity with a partner. The findings are consistent with the idea that some women may be more sensitive to changes in T than others. No relationship was found between negative mood, as assessed by the Beck Depression Inventory, and changes in T, FT, or DHEA-S.

  5. Effects of menstrual cycle, oral contraception, and training on exercise-induced changes in circulating DHEA-sulphate and testosterone in young women.

    PubMed

    Enea, C; Boisseau, N; Ottavy, M; Mulliez, J; Millet, C; Ingrand, I; Diaz, V; Dugué, B

    2009-06-01

    The objective of this study was to ascertain the effects of menstrual cycle, oral contraception, and training status on the exercise-induced changes in circulating DHEA-sulphate and testosterone in young women. Twenty-eight healthy women were assigned to an untrained group (n = 16) or a trained group (n = 12) depending on their training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-). The trained group was composed of OC+ subjects only. All the OC+ subjects were taking the same low-dose oral contraception. Three laboratory sessions were organised in a randomised order: a prolonged exercise test until exhaustion, a short-term exhaustive exercise test, and a control session. Blood specimens were collected before, during and after the exercise tests and at the same time of the day during the control session. Basal circulating testosterone was significantly lower in trained as compared to untrained subjects. In all subjects, the prolonged exhaustive exercise induced a significant increase in circulating DHEA-s and testosterone. The short-term exercise induced a significant increase in circulating DHEA-s in untrained eumenorrheic and in trained OC users only. Menstrual phases in OC- did not influence the responses. It was found that exhaustive physical exercise induced an increase in circulating DHEA-s and testosterone in young women. Oral contraception may limit short-term exercise-induced changes.

  6. The effect of testosterone and a nutritional supplement on hospital admissions in under-nourished, older people

    PubMed Central

    2011-01-01

    Background Weight loss and under-nutrition are relatively common in older people, and are associated with poor outcomes including increased rates of hospital admissions and death. In a pilot study of 49 undernourished older, community dwelling people we found that daily treatment for one year with a combination of testosterone tablets and a nutritional supplement produced a significant reduction in hospitalizations. We propose a larger, multicentre study to explore and hopefully confirm this exciting, potentially important finding (NHMRC project grant number 627178). Methods/Design One year randomized control trial where subjects are allocated to either oral testosterone undecanoate and high calorie oral nutritional supplement or placebo medication and low calorie oral nutritional supplementation. 200 older community-dwelling, undernourished people [Mini Nutritional Assessment score <24 and either: a) low body weight (body mass index, in kg/m2: <22) or b) recent weight loss (>7.5% over 3 months)]. Hospital admissions, quality-adjusted life years, functional status, nutritional health, muscle strength, body composition and other variables will be assessed. Discussion The pilot study showed that combined treatment with an oral testosterone and a supplement drink was well tolerated and safe, and reduced the number of people hospitalised and duration of hospital admissions in undernourished, community dwelling older people. This is an exciting finding, as it identifies a treatment which may be of substantial benefit to many older people in our community. We now propose to conduct a multi-centre study to test these findings in a substantially larger subject group, and to determine the cost effectiveness of this treatment. Trial registration Australian Clinical Trial Registry: ACTRN 12610000356066 PMID:22023735

  7. Salivary and plasma free testosterone and androstenedione levels in women using oral contraceptives containing desogestrel or levonorgestrel.

    PubMed

    Swinkels, L M; Meulenberg, P M; Ross, H A; Benraad, T J

    1988-07-01

    The effect of oral contraceptives (OC) containing a combination of ethinyloestradiol (EE2) and either desogestrel (Dg/EE2) or levonorgestrel (Lg/EE2) on plasma concentrations of sex hormone binding globulin (SHBG), total testosterone (T), free T, total androstenedione (A), free A and on salivary T and A concentrations have been studied. SHBG concentrations were higher in the Dg/EE2 group than in the Lg/EE2 group. Total T, measured by RIA with prior extraction and chromatography, is also higher in the Dg/EE2 group. Per cent free T was lower in the Dg/EE2 group. Plasma free T and free A concentrations were the same in both groups. However, free T and free A were significantly lower in the OC-groups than in controls. In contrast, by direct assay, no difference in total T was observed between the OC-groups. Since the per cent free T was lower in the Dg/EE2 group, it would be concluded that free T in the Dg/EE2 group is lower than in the Lg/EE2 group. Salivary free T and free A concentrations did not differ between control and OC-groups. There was good correlation between salivary and free hormone concentrations within each group. We conclude that the concentrations of androgens in saliva do not necessarily directly reflect their free concentrations in plasma.

  8. Testosterone therapy has positive effects on anthropometric measures, metabolic syndrome components (obesity, lipid profile, Diabetes Mellitus control), blood indices, liver enzymes, and prostate health indicators in elderly hypogonadal men.

    PubMed

    Canguven, O; Talib, R A; El Ansari, W; Yassin, D-J; Salman, M; Al-Ansari, A

    2017-03-10

    To alleviate late-onset hypogonadism, testosterone treatment is offered to suitable patients. Although testosterone treatment is commonly given to late-onset hypogonadism patients, there remains uncertainty about the metabolic effects during follow-ups. We assessed the associations between testosterone treatment and wide range of characteristics that included hormonal, anthropometric, biochemical features. Patients received intramuscular 1,000 mg testosterone undecanoate for 1 year. Patient anthropometric measurements were undertaken at baseline and at each visit, and blood samples were drawn at each visit, prior to the next testosterone undecanoate. Eighty-eight patients (51.1 ± 13.0 years) completed the follow-up period. Testosterone treatment was associated with significant increase in serum testosterone levels and significant stepladder decrease in body mass index, total cholesterol, triglycerides and glycated haemoglobin from baseline values among all patients. There was no significant increase in liver enzymes. There was an increase in haemoglobin and haematocrit, as well as in prostate-specific antigen and prostate volume, but no prostate biopsy intervention was needed for study patients during 1-year testosterone treatment follow-up. Testosterone treatment with long-acting testosterone undecanoate improved the constituents of metabolic syndrome and improved glycated haemoglobin in a stepladder fashion, with no adverse effects.

  9. Single dose sublingual testosterone and oral sildenafil vs. a dual route/dual release fixed dose combination tablet: a pharmacokinetic comparison

    PubMed Central

    van Rooij, Kim; de Leede, Leo; Frijlink, Henderik W.; Koppeschaar, Hans P. F.; Olivier, Berend; Tuiten, Adriaan

    2016-01-01

    Aim The aim was to compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for female sexual interest/arousal disorder. The prototype (formulation 1) consists of a testosterone solution for sublingual administration and a sildenafil tablet that is administered 2.5 h later. The dual route/dual release fixed dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner core of sildenafil with a polymeric time delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal non‐adherence through circumventing the relatively complex temporal dosing scheme. Methods Twelve healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N‐desmethyl‐sildenafil. Results Formulation 2 had a higher maximum concentration (C max) for testosterone, 8.06 ng ml–1 (95% confidence interval [CI] 6.84, 9.28) and higher area under the plasma concentration–time curve (AUC), 7.69 ng ml–1 h (95% CI 6.22, 9.16) than formulation 1, 5.66 ng ml–1 (95% CI 4.63, 6.69) and 5.12 ng ml–1 h (95% CI 4.51, 5.73), respectively. Formulation 2 had a lower C max for sildenafil, 173 ng ml–1 (95% CI 126, 220) and a lower AUC, 476 ng ml–1 h (95% CI 401, 551) than formulation 1, 268 ng ml–1 (95% CI 188, 348) and 577 ng ml–1 h (95% CI 462, 692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40, 3.10). Conclusions The dual route/dual release fixed dose combination tablet fulfilled its design criteria and is considered suitable for further clinical testing. What is Already Known about this Subject Female sexual interest/arousal disorder (FSIAD) is a

  10. Testosterone Therapies.

    PubMed

    Khera, Mohit

    2016-05-01

    There are numerous testosterone formulations now available, and patients and clinicians should take into account the "4 Cs": cost, compliance, convenience, and concentration levels. Testosterone is a natural contraceptive and should not be used in men trying to achieve a pregnancy. All testosterone gels and solutions have an increased risk of transference, and there should be increased caution when in contact with children and pregnant women.

  11. Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in Men with Testosterone Deficiency Syndrome

    PubMed Central

    Jung, Hyun Jin

    2016-01-01

    Purpose We aimed to evaluate the effect of testosterone replacement therapy (TRT) on cognitive function and depression in men with testosterone deficiency syndrome. Materials and Methods We carried out a prospective, placebo-controlled trial involving 106 men with total testosterone levels <3.3 ng/mL and symptoms of hypogonadism. Based on whether the patients received TRT (injection with 1,000 mg testosterone undecanoate) or a placebo (advice to modify lifestyle), the study population was divided into a TRT group (n=54) and a control group (n=52). Results The age among patients in the TRT and control groups was 56.7±12.6 years and 57.8±11.4 years, respectively (p> 0.05). At baseline, no significant differences between the TRT and control groups were noted regarding serum testosterone or prostate-specific antigen levels, or regarding the scores for aging symptoms (Aging Males' Symptoms scale), erectile function (5-item International Index of Erectile Function questionnaire), cognitive function (Korean Mini-Mental State Examination), and depression (Beck Depression Inventory). At 8 months after intervention total serum testosterone levels and erectile function scores had significantly increased (p<0.05), whereas the scores for aging symptoms and depression had significantly decreased (p<0.05) in the TRT group; no significant improvement in any parameters was noted for the control group. Notably, significant improvement in cognitive function was noted among patients with cognitive impairment at baseline (cognitive function score <25) who received TRT. Conclusions TRT may be considered in men with testosterone deficiency syndrome if low testosterone levels are associated with depression or cognitive impairment. PMID:28053949

  12. Low-intermediate dose testosterone replacement therapy by different pharmaceutical preparations improves frailty score in elderly hypogonadal hyperglycaemic patients.

    PubMed

    Strollo, Felice; Strollo, Giovanna; Morè, Massimo; Magni, Paolo; Macchi, Chiara; Masini, Maria Angela; Carucci, Iarba; Celotti, Fabio; Ruscica, Massimiliano; Gentile, Sandro

    2013-06-01

    An open-label follow-up study of low-to-intermediate dose testosterone replacement therapy (TRT) was conducted in 64 overweight patients (aged 65-75 years) with late onset hypogonadism (LOH) and increased fasting plasma glucose (FPG). Patients were subdivided into four treatment groups: oral testosterone (T) (T undecanoate, 80 mg/d), transmucosal T (60 mg/d), transdermal T (30 mg/d) or no treatment (control), and evaluated at 0 and 6 months. FPG, hemoglobin (Hb), prostate-specific antigen (PSA) and total T were measured and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body mass index (BMI), waist circumference, fitness level (6-min walking test), Aging Males' Symptoms (AMS) scale, handgrip strength and energy expenditure with physical activity (Minnesota questionnaire for Leisure Time Physical Activity (LTPA)) were evaluated and a "frailty score" (based on: grip strength, gait speed and LTPA) was calculated. T levels increased in all treatment groups; the oral T group had values still in the hypogonadal range (5.9 ± 1.1 nmol/L). PSA and Hb concentrations did not change in any group. BMI, waist circumference, FPG and HOMA-IR improved in all T-treated groups after 6 months, with a greater effect seen with transmucosal and transdermal T compared with oral T. This study indicates that low-to-intermediate dose TRT may be safely utilized in LOH patients to ameliorate somatic and psychological frailty symptoms in association with improved anthropometric and glycometabolic parameters in aging, overweight men with LOH and impaired fasting glucose.

  13. The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

    PubMed Central

    Zimmerman, Y.; Eijkemans, M.J.C.; Coelingh Bennink, H.J.T.; Blankenstein, M.A.; Fauser, B.C.J.M.

    2014-01-01

    BACKGROUND Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T. METHODS A review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T. RESULTS A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18–40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) −0.49 nmol/l (−0.55, −0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0

  14. [Testosterone therapy].

    PubMed

    Diemer, T; Hauptmann, A; Wagenlehner, F M E

    2016-04-01

    Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency.

  15. Effect of estrogen and testosterone replacement therapy on cognitive fatigue.

    PubMed

    Möller, Marika Christina; Rådestad, Angelique Flöter; von Schoultz, Bo; Bartfai, Aniko

    2013-02-01

    Both estrogen and testosterone insufficiency has been associated with reduced psychological well-being including fatigue. However, hormonal replacement studies on fatigue are rare. Therefore, we wanted to study the effect of testosterone and estrogen replacement therapy on cognitive fatigue and the relation between sex hormone levels and cognitive fatigue in oophorectomized women. Fifty women with surgically induced menopause (mean age: 54.0 ± 2.9 years) were randomly assigned to treatment with estradiol valerate in combination with testosterone undecanoate or placebo for 24 weeks in a double-blind cross-over study. Neuropsychological tests and questionnaires were used to assess cognitive fatigue and psychological well-being. Cognitive fatigue was significantly associated to poor self-rated health and higher body mass index but not to general psychological well-being or sex hormone levels. Treatment with testosterone + estrogen had no significant effect on cognitive fatigue but the results indicated a curvilinear relation for hormonal levels. The estrogen/testosterone ratio was more related to functions rather than high or low hormone levels per se. We found that cognitive fatigue is frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. A well-balanced ratio between estrogen and testosterone levels may be important for cognitive fatigue.

  16. Testosterone Buccal

    MedlinePlus

    ... left and right of the two front teeth). Alternate sides at every dose so that you never ... thoughts or beliefs that have no basis in reality). People who use higher doses of testosterone than ...

  17. Supplementation with vitamin D does not increase serum testosterone levels in healthy males.

    PubMed

    Jorde, R; Grimnes, G; Hutchinson, M S; Kjærgaard, M; Kamycheva, E; Svartberg, J

    2013-09-01

    Cross-sectional studies indicate a positive relation between serum 25-hydroxyvitamin D [25(OH)D] and testosterone. It is not known if this relation is causal, which in theory could be in both directions. A cross-sectional population based study was designed with pooled data from 3 vitamin D randomized clinical trials (RCTs) performed in Tromsø with weight reduction, insulin sensitivity, and depression scores as endpoints, and one testosterone RCT in subjects with low serum testosterone (<11.0 nmol/l) and with body composition as endpoint. Serum 25(OH)D and androgens were measured in 893 males in the cross-sectional part, at baseline and after 6-12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week vs. placebo in the vitamin D RCTs (n=282), and at baseline and after one year treatment with testosterone undecanoate 1 000 mg or placebo injections (at baseline and after 6, 16, 28, and 40 weeks) in the testosterone RCT (n=37). In the cross-sectional study, serum 25(OH)D was found to be a significant and positive predictor of serum testosterone. In the vitamin D RCTs, no significant effect on serum total or free testosterone levels was seen, and in the testosterone RCT no significant effect on serum 25(OH)D was seen. This was unchanged in sub-analyses in subjects with low serum 25(OH)D (or testosterone) levels. In conclusion, in subjects without significant vitamin D deficiency, there is no increase in serum testosterone after high dose vitamin D supplementation. Similarly, in subjects with moderately low serum testosterone levels, substitution with testosterone does not increase serum 25(OH)D.

  18. Effect of multiple oral doses of androgenic anabolic steroids on endurance performance and serum indices of physical stress in healthy male subjects.

    PubMed

    Baume, Norbert; Schumacher, Yorck Olaf; Sottas, Pierre-Edouard; Bagutti, Carlo; Cauderay, Michel; Mangin, Patrice; Saugy, Martial

    2006-11-01

    Anabolic androgenic steroids (AAS) are doping agents that are mostly used for improvement of strength and muscle hypertrophy. In some sports, athletes reported that the intake of AAS is associated with a better recovery, a higher training load capacity and therefore an increase in physical and mental performances. The purpose of this study was to evaluate, the effect of multiple doses of AAS on different physiological parameters that could indirectly relate the physical state of athletes during a hard endurance training program. In a double blind settings, three groups (n = 9, 8 and 8) were orally administered placebo, testosterone undecanoate or 19-norandrostenedione, 12 times during 1 month. Serum biomarkers (creatine kinase, ASAT and urea), serum hormone profiles (testosterone, cortisol and LH) and urinary catecholamines (noradrenalin, adrenalin and dopamine) were evaluated during the treatment. Running performance was assessed before and after the intervention phase by means of a standardized treadmill test. None of the measured biochemical variables showed significant impact of AAS on physical stress level. Data from exercise testing on submaximal and maximal level did not reveal any performance differences between the three groups or their response to the treatment. In the present study, no effect of multiple oral doses of AAS on endurance performance or bioserum recovery markers was found.

  19. Direct radioimmunoassay (RIA) of salivary testosterone: correlation with free and total serium testosterone

    SciTech Connect

    Vittek, J.; L'Hommedieu, D.G.; Gordon, G.G.; Rappaport, S.C.; Southren, A.L.

    1985-08-26

    Simple and sensitive direct RIA for determination of salivary testosterone was developed by using RSL NOSOLVEX TM (125 1) kit produced by Radioassay System Laboratories (Carcon, California). In addition, a relationship between salivary and serum free and total testosterone concentrations was studied in randomly selected 45 healthy subjects, 5 females on oral contraceptive pills and 28 hypertensive patients on various treatment regimens. The lowest weight of testosterone detectable by the modified method was equivalent to 1 pg/ml of saliva, taking into account analytical variability. Intra- and interassay coefficients of variation were 5.09 +/- 2.7% and 8.2 +/- 5.9% respectively. Statistically significant correlations were found between salivary and serum free testosterone (r = 0.97) and salivary and serum total testosterone concentrations (r = 0.70 - 0.87). The exception to this was a group of hypertensive females in which no correlation (r = 0.14) between salivary and total serum testosterone was found. It is also of interest that, while salivary testosterone was significantly increased in subjects taking oral contraceptives and most of the hypertensive patients, the total serum testosterone concentration was in normal range. These findings suggest that the determination of salivary testosterone is a reliable method to detect changes in the concentration of available biologically active hormone in the circulation. 21 references, 4 figures, 1 table.

  20. Effect of testosterone replacement therapy on bone mineral density in patients with Klinefelter syndrome.

    PubMed

    Jo, Dae Gi; Lee, Hyo Serk; Joo, Young Min; Seo, Ju Tae

    2013-11-01

    Klinefelter syndrome (KS) is related to testicular insufficiency, which causes low testosterone levels in serum. Generally, sex hormone levels and bone mineral density (BMD) are lower in patients with KS than normal. We investigated the effects of testosterone replacement on serum testosterone levels and BMD in KS patients. From December 2005 to March 2008, 18 KS patients with a 47, XXY karyotype were treated with initial intramuscular injections of long-acting testosterone undecanoate (Nebido®, 1000 mg/4 mL) at baseline and second injections after six weeks. An additional four injections were administered at intervals of 12 weeks after the second injection. BMD was measured at the lumbar spine (L2-4), the left femoral neck and Ward's triangle, using dual energy X-ray absorptiometry. Medical histories, physical examinations and prostate specific antigen, hematology and serum chemistry were conducted for each patient. In addition, total testosterone and sex hormone-binding globulin levels were measured. Following testosterone replacement, mean serum total testosterone increased significantly from baseline (0.90 vs. 4.51 ng/mL, p<0.001), and total testosterone rose to normal levels after replacement in all patients. The mean BMD of the lumbar spine increased significantly (0.91 vs. 0.97 g/cm², p<0.001). Similar increases of BMD were also observed at the femoral neck, but this increase was not significant. These findings suggest that testosterone replacement therapy may be effective in treating BMD deficiency in men with testosterone deficiency, especially those with Klinefelter syndrome.

  1. Micturition dysfunction in four-month old ovariectomized rats: Effects of testosterone replacement.

    PubMed

    Bonilla-Becerra, Sandra M; de Oliveira, Mariana G; Calmasini, Fabiano B; Rojas-Moscoso, Julio A; Zanesco, Angelina; Antunes, Edson

    2017-06-15

    Androgen deficiency has been implicated in urological complications of postmenopausal women. This study examined the effects of testosterone replacements on the lower urinary tract dysfunction in 4-month old ovariectomized (OVX) rats. Sprague-Dawley female rats were OVX bilaterally. Three months later, rats received single intramuscular injections of testosterone undecanoate. Cystometric study, and bladder and urethra smooth muscle reactivities were evaluated. Ovariectomy reduced by 65% (p<0.05) the serum testosterone levels. Testosterone replacement at 5mg/kg restored serum hormone levels to baseline, whereas 10mg/kg produced 14-fold higher testosterone levels. OVX rats exhibited significant increases of body weight, perigonadal fat and blood pressure, and reduced uterus weight, but none of these parameters were changed by testosterone replacements. OVX rats exhibited micturition dysfunction characterized by increases of basal pressure, threshold pressure, voiding frequency and post-voiding pressure. In addition, the bladder contractions induced by electrical-field stimulation (EFS) and carbachol were significantly reduced, whereas angiotensin II-induced urethral contractions were significantly increased in OVX rats. Testosterone replacement at 10mg/kg (but not at 5mg/kg) dose fully normalized the in vivo micturition dysfunction, as well as the in vitro bladder and urethral alterations. Testosterone (10mg/kg) also significantly potentiated the bladder relaxations induced by the β3-adrenoceptor agonist mirabegron. The protective effects of testosterone were not modified by concomitant treatment with the aromatase inhibitor letrozole (2.5mg/kg, 4weeks). The improvement of micturition dysfunction by testosterone replacement suggests that androgen therapy might be of therapeutic benefit for urological complications associated with post-menopause. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults.

    PubMed

    Søeborg, Tue; Frederiksen, Hanne; Mouritsen, Annette; Johannsen, Trine Holm; Main, Katharina Maria; Jørgensen, Niels; Petersen, Jørgen Holm; Andersson, Anna-Maria; Juul, Anders

    2014-11-01

    The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Alternatives to testosterone replacement: testosterone restoration.

    PubMed

    McCullough, Andrew

    2015-01-01

    The European Male Aging Study has demonstrated that the hypogonadism of male aging is predominantly secondary. Theoretically with appropriate stimulation from the pituitary, the aging testis should be able to produce eugonadal levels of testosterone. The strategies for the treatment of late onset hypogonadism (LOH) have focused on replacement with exogenous testosterone versus restoration of endogenous production. The purpose of this article is to review existing peer-reviewed literature supporting the concept of restoration of endogenous testosterone in the treatment of LOH.

  4. Testosterone Therapy in Men

    MedlinePlus

    ... softness of the testicles Size of the penis Measurement of testosterone levels Generally, blood levels of testosterone ... levels may be different in different laboratories. Morning measurement (when levels are highest) is recommended. Illness, malnutrition, ...

  5. Assays of Serum Testosterone.

    PubMed

    Herati, Amin S; Cengiz, Cenk; Lamb, Dolores J

    2016-05-01

    The diagnosis of male hypogonadism depends on an assessment of the clinical signs and symptoms of hypogonadism and serum testosterone level. Current clinical laboratory testosterone assay platforms include immunoassays and mass spectrometry. Despite significant advances to improve the accuracy and precision of the currently available assays, limited comparability exists between assays at the lower and upper extremes of the testosterone range. Because of this lack of comparability, there is no current gold standard assay for the assessment of total testosterone levels.

  6. Testosterone and Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    1994-01-01

    Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…

  7. Testosterone and Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    1994-01-01

    Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…

  8. Effect of orchiectomy and testosterone replacement on lower urinary tract function in anesthetized rats.

    PubMed

    Cheng, Chen-Li; de Groat, William C

    2016-11-01

    Lower urinary tract (LUT) symptoms (LUTS), including frequency, urgency, incomplete voiding, and slow stream, are common in both men and women with advancing age. The most common cause for LUTS in aging men is benign prostatic hyperplasia. Some studies have also revealed an inverse association of serum testosterone levels with LUTS; however, the underlying mechanisms by which gonadal hormones affect the LUT have not been clarified. In the present study, we examined the effect of orchiectomy and testosterone replacement on LUT function in adult male Sprague-Dawley rats. Six weeks after bilateral orchiectomy or sham operations and 3 wk after injection of long-acting testosterone undecanoate (100 mg/kg im), transvesical cystometry and external urethral sphincter electromyogram (EUS EMG) recordings were performed under urethane anesthesia. The micturition reflex was elicited in both sham and orchiectomized animals. In orchiectomized rats, volume threshold for inducing micturition decreased by 47.6%; however, contraction amplitude, duration, and voiding efficiency were similar in sham and orchiectomized rats. The active period during EUS EMG bursting was lengthened during micturition in orchiectomized animals. Testosterone treatment, which normalized plasma testosterone levels, reversed these changes but also increased the duration of EUS EMG bursting. Orchiectomy also reduced mean voiding flow rate estimated from the duration of EUS EMG bursting, an effect that was not reversed by testosterone. The results indicate that orchiectomy affects both the active and passive properties of the bladder and urethra, and that many, but not all, of the changes can be reversed by testosterone. Copyright © 2016 the American Physiological Society.

  9. Testosterone therapy in men with Crohn's disease improves the clinical course of the disease: data from long-term observational registry study.

    PubMed

    Nasser, Mahmoud; Haider, Ahmad; Saad, Farid; Kurtz, Winfried; Doros, Gheorghe; Fijak, Monika; Vignozzi, Linda; Gooren, Louis

    2015-06-01

    Crohn's disease is an inflammatory chronic bowel disease characterized by an imbalanced production of pro-inflammatory mediators (tumor necrosis factor-α) and an increased recruitment of leukocytes to the site of inflammation. Low serum testosterone is associated with an increase in inflammatory factors, while testosterone administration reduces them. There is evidence for an immunomodulatory effect of testosterone on differentiation of regulatory T cells. The research was carried out in clinics in Germany and Syria. The study was a cumulative, prospective, registry study with an increasing number of men over time receiving testosterone. While men diagnosed with Crohn's disease received appropriate treatment for Crohn's disease, they were tested for testosterone deficiency (cut-off point ≤12.1 nmol/L). In total, 92 men received parenteral testosterone undecanoate 1000 mg/12 weeks for up to 7 years. Fourteen men opted not to receive testosterone and served as a comparison group. In men receiving testosterone, the Crohn's Disease Activity Index declined from 239.36±36.96 to 71.67±3.26 at 84 months (p<0.0001 vs. baseline). C-reactive protein levels decreased from 12.89±8.64 to 1.78±1.37 mg/L at 84 months (p<0.0001 vs. baseline). Leukocyte count decreased from 11.93±2.85 to 6.21±1.01×109/L (p<0.0001 at 84 months vs. baseline). No changes were observed in the comparison group. There were no significant side effects of testosterone. Normalizing serum testosterone in hypogonadal men with Crohn's disease had a positive effect on the clinical course, also evidenced by biochemical parameters. Testosterone administration appeared safe.

  10. Testosterone and Occupational Achievement.

    ERIC Educational Resources Information Center

    Dabbs, James M., Jr.

    1992-01-01

    Archival data on 4,462 military veterans linked higher levels of serum testosterone to lower-status occupations. A structural equation model was supported in which higher testosterone, mediated through lower intellectual ability, greater antisocial behavior, and lower education, leads away from white-collar occupations. Contains 49 references.…

  11. Testosterone and Social Behavior

    ERIC Educational Resources Information Center

    Booth, Alan; Granger, Douglas A.; Mazur, Allan; Kivlighan, Katie T.

    2006-01-01

    Popular perceptions of the effect of testosterone on "manly" behavior are inaccurate. We need to move away from such simplistic notions by treating testosterone as one component along with other physiological, psychological and sociological variables in interactive and reciprocal models of behavior. Several hormones can now be measured in saliva,…

  12. Testosterone and Occupational Achievement.

    ERIC Educational Resources Information Center

    Dabbs, James M., Jr.

    1992-01-01

    Archival data on 4,462 military veterans linked higher levels of serum testosterone to lower-status occupations. A structural equation model was supported in which higher testosterone, mediated through lower intellectual ability, greater antisocial behavior, and lower education, leads away from white-collar occupations. Contains 49 references.…

  13. Testosterone and Social Behavior

    ERIC Educational Resources Information Center

    Booth, Alan; Granger, Douglas A.; Mazur, Allan; Kivlighan, Katie T.

    2006-01-01

    Popular perceptions of the effect of testosterone on "manly" behavior are inaccurate. We need to move away from such simplistic notions by treating testosterone as one component along with other physiological, psychological and sociological variables in interactive and reciprocal models of behavior. Several hormones can now be measured in saliva,…

  14. [65-month testosterone replacement therapy for androgen deficiency-induced ED: a case report and review of the literature].

    PubMed

    Jiang, Tao; Zheng, Lei; Sun, Dong-Chen; Li, Quan-Lin; Zhang, Zhi-Wei; Wang, Fa-Peng; Wang, Qi-Fei; Jiang, Hui

    2014-02-01

    To explore the mechanism of erectile dysfunction (ED) with testosterone deficiency and discuss the feasibility of long-term testosterone replacement therapy (TRT) by observing a case of ED with testosterone deficiency treated by TRT for 65 months. We treated an ED patient with testosterone deficiency by TST for 65 months, and evaluated the therapeutic effects by analyzing his IIEF-5 score, dynamic changes in testosterone, PSA, hemoglobin and red blood cell count, and adverse events. The patient was a 46-year-old man, with an IIEF-5 score of 7, baseline serum total testosterone (TT) of 2.79 ng/ml, and no response to phosphodiesterases-5 inhibitors (PDE5i). He was diagnosed with late-onset hypogonadism (LOH) and treated by TRT: testosterone undecanoate at 80 mg bid po for the first 2 weeks and then at 40 mg bid po. Two months after medication, the TT level was increased to normal (3.45 ng/ml), and physical fitness and anxiety symptoms were markedly improved, with no significant improvement in sexual function. Then we administered PDE5i on demand in addition, which elevated his IIEF-5 score to > 21. The combined medication of TRT and on-demand PDE5i lasted for 45 months followed by TRT alone for another 18 months. The patient was restored to normal penile erection and sexual satisfaction, with the IIEF-5 score remaining at > 21. Regular follow-up revealed no significant abnormalities in the testosterone level, PSA, and routine blood tests. TRT enhances the effect of PDE5i in the treatment of androgen deficiency-induced ED, and long-term TRT is safe and effective for androgen deficiency.

  15. Testosterone and musical talent.

    PubMed

    Hassler, M

    1991-01-01

    Two recently published hypotheses on the biological basis of special talents are discussed in relation to experimental data obtained from musical composers, instrumentalists, painters, and non-musicians, and from adolescent boys and girls with different levels of musical capacities. Both hypotheses assign an important influence to prenatal testosterone effects on the developing brain. Geschwind and Galaburda (1985) predict that subjects with special talents may have anomalous hemispheric dominance for verbal material. This was confirmed experimentally in adolescents and in adults using a dichotic listening task to assess functional lateralization. Hassler and Nieschlag (1989) expect musicians of both sexes to be psychologically androgynous and to have current testosterone levels that differ from sex-typed males and females. Salivary testosterone was measured in adults and in adolescents. Creative musical behavior was associated with very low testosterone values in males, and with high testosterone levels in females. Sexual activity level and motivation did not differ between males with testosterone levels less than or equal to 200 pmol/l and those with greater than 220 pmol/l. We tentatively suggest from our data that, among a complex interaction of biological and social factors, an optimal testosterone range may exist for the expression of creative musical behavior. Exceeding the range in the course of adolescence may be detrimental for musical creativity in boys.

  16. Testosterone replacement therapy does not promote priapism in hypogonadal men with sickle cell disease: 12-month safety report.

    PubMed

    Morrison, B F; Reid, M; Madden, W; Burnett, A L

    2013-07-01

    Hypogonadism, which is highly prevalent in men with sickle cell disease (SCD), affects quality of life and causes great morbidity. The safety of testosterone replacement therapy (TRT) in SCD in relation to priapism episodes is relatively unknown. Our aim was to monitor the safety of TRT in a cohort of seven hypogonadal men with SCD. Testosterone undecanoate (Nebido) 1 g was administered intramuscularly to adult men with homozygous SCD (Hb SS) having hypogonadism [serum total testosterone ≤12.0 nmol/L (346 ng/dL), reference range 12.5-38.1 nmol/L (360-1098 ng/dL)] for 12 months. Serum total testosterone, haemoglobin, haematocrit, renal and liver function tests, glucose and PSA measurements were done at baseline and 12-month follow-up. Trough serum total testosterone, haemoglobin and haematocrit were measured three monthly. Priapism events and adverse drug events were assessed every 3 months. International Index of Erectile Function (IIEF), Androgen Deficiency in the Ageing Male (ADAM) and World Health Organization Quality of Life (WHOQOL) questionnaires were administered at baseline, 6 and 12 months. Seven men with a mean age of 34.4 years were treated. Median total testosterone increased from 10.6 to 11.2 nmol/L (p = 0.46). Median serum lactate dehydrogenase levels decreased from 1445 to 1143.5 IU/L (p < 0.05), while all other laboratory indices remained stable. Injection site pain was the most frequently reported adverse event, with no increases in painful crises, hypersensitivity or oedema. After TRT, there was no significant increase in priapism frequency. Median questionnaire scores were increased for the IIEF (46-68, p = 0.018), reduced for ADAM (5.0-2.0, p = 0.016) and unchanged for WHOQOL (98-103, p = 0.086). TRT using testosterone undecanoate with eugonadal intent for hypogonadism appears to be safe in men with SCD. This treatment does not appear to promote priapism occurrences and rather it possibly improves sexual function. Future prospective

  17. Monitoring testosterone levels in testosterone-treated men.

    PubMed

    Winters, Stephen J

    2016-01-01

    Dose adjustment with transdermal testosterone preparations should recognize the variability of serum total testosterone levels between applications and over the course of 24 h. Dose adjustments are also made difficult by between-laboratory assay variability. Low SHBG with obesity and diabetes lowers the total testosterone level, and free or bioavailable testosterone may prove to be a better choice for monitoring the progress and dosing of testosterone-treated men with adult onset hypogonadism.

  18. Testosterone replacement therapy improves erythrocyte membrane lipid composition in hypogonadal men.

    PubMed

    Angelova, Petya; Momchilova, Albena; Petkova, Diana; Staneva, Galya; Pankov, Roumen; Kamenov, Zdravko

    2012-09-01

    The aim of this study was to investigate the effects of testosterone replacement therapy (TRT) on erythrocyte membrane (EM) lipid composition and physico-chemical properties in hypogonadal men. EM isolated from three patients before and after TRT with injectable testosterone undecanoate or testosterone gel were used for analysis of the phospholipid and fatty acid composition, cholesterol/phospholipid ratio, membrane fluidity, ceramide level and enzyme activities responsible for sphingomyelin metabolism. TRT induced increase of phosphatidylethanolamine (PE) in the EMs and sphingomyelin. Reduction of the relative content of the saturated palmitic and stearic fatty acids and a slight increase of different unsaturated fatty acids was observed in phosphatidylcholine (PC). TRT also induced decrease of the cholesterol/total phospholipids ratio and fluidization of the EM. The TRT induced increase of PE content and the reduction of saturation in the PC acyl chains induced alterations in the structure of EM could result in higher flexibility of the erythrocytes. The increase of the SM-metabolizing enzyme neutral sphingomyelinase, which regulates the content of ceramide in membranes has a possible impact on the SM signaling pathway. We presume that the observed effect of TRT on the composition and fluidity of the EM contributes for improvement of blood rheology and may diminish the thrombosis risk. Larger studies are needed to confirm the findings of this pilot study.

  19. Sexual Health: Testosterone Therapy

    MedlinePlus

    ... Testosterone helps maintain men's: Bone density Fat distribution Muscle strength and mass Facial and body hair Red blood ... changes are possible, including increased body fat, reduced muscle bulk and strength, and decreased bone density. Swollen or tender breasts ( ...

  20. A close relationship between androgen levels and eumelanogenesis in the teleost red seabream (Pagrus major): Quantitative analysis of its seasonal variation and effects of oral treatment with methyl-testosterone.

    PubMed

    Adachi, Kohsuke; Wakamatsu, Kazumasa; Ito, Shosuke; Matsubara, Hajime; Nomura, Kazuharu; Tanaka, Hideki; Kato, Keitaro

    2010-06-01

    Male and female teleost seabream (Pagrus major) were examined for seasonal variation of eumelanin, pheomelanin, 11-ketotestosterone (11KT, fish androgen), lightness (L* value) and Gonad Somatic Index (GSI: gonad mass/body massx100). In males, levels of pyrrole-2,3,5-tricarboxylic acid (a marker of eumelanin), 11KT and the GSI increased sharply from September and plateaued in March and April when the fish are sexually mature. These results are consistent with the lightness of their body color. Using the data from males, a high correlation was observed for all combinations of those four variables (PTCA, 11KT, lightness and GSI). In females, little change was observed in those variables except for the GSI. 4-Amino-3-hydroxyphenylalanine (a marker of pheomelanin) was also analyzed, but it was below the detection limit at all times. Oral treatment of juvenile red seabream with synthetic androgen methyl-testosterone for 2 months induced eumelanin accumulation about 3 times higher than the control. These data show that there is a close relationship between androgen levels and eumelanin accumulation in teleosts. This is the first report that androgen affects melanin accumulation in a dose-dependent manner. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Testosterone, thrombophilia, and thrombosis.

    PubMed

    Glueck, Charles J; Richardson-Royer, Caitlin; Schultz, Reiker; Burger, Tim; Labitue, Fanta; Riaz, Muhammad K; Padda, Jagjit; Bowe, Dedrick; Goldenberg, Naila; Wang, Ping

    2014-01-01

    We describe thrombosis, deep venous thrombosis (DVT) pulmonary embolism (PE; n = 9) and hip-knee osteonecrosis (n = 5) that developed after testosterone therapy (median 11 months) in 14 previously healthy patients (13 men and 1 woman; 13 Caucasian and 1 African American), with no antecedent thrombosis and previously undiagnosed thrombophilia-hypofibrinolysis. Of the 14 patients, 3 were found to be factor V Leiden heterozygotes, 3 had high factor VIII, 3 had plasminogen activator inhibitor 1 4G4G homozygosity, 2 had high factor XI, 2 had high homocysteine, 1 had low antithrombin III, 1 had the lupus anticoagulant, 1 had high anticardiolipin antibody Immunoglobulin G, and 1 had no clotting abnormalities. In 4 men with thrombophilia, DVT-PE recurred when testosterone was continued despite therapeutic international normalized ratio on warfarin. In 60 men on testosterone, 20 (33%) had high estradiol (E2 >42.6 pg/mL). When exogenous testosterone is aromatized to E2, and E2-induced thrombophilia is superimposed on thrombophilia-hypofibrinolysis, thrombosis occurs. The DVT-PE and osteonecrosis after starting testosterone are associated with previously undiagnosed thrombophilia-hypofibrinolysis. Thrombophilia should be ruled out before administration of exogenous testosterone.

  2. Biotransformation of testosterone and testosterone heptanoate by four filamentous fungi.

    PubMed

    Ghasemi, Sabrieh; Mohajeri, Maryam; Habibi, Zohreh

    2014-12-01

    The microbial transformations of testosterone and testosterone heptanoate by four fungi: Absidia griseolla var. igachii PTCC 5260, Acremonium chrysogenu PTCC 5271, Fusarium fujikuroi PTCC 5144, and Fusarium solani complex PTCC 5285 were investigated for the first time. Incubation of testosterone heptanoate with F. fujikuroi and F. solani yielded three metabolites, which were isolated and characterized as testosterone, androst-4-ene-3,17-dione, and 6β-hydroxy testosterone. 6β-Hydroxy testosterone was the major metabolite obtained from testosterone heptanoate biotransformation by two fungal species. A. griseolla and A. chrysogenu produced 14α-hydroxy testosterone as major metabolite, together with testosterone and 6β-hydroxy testosterone in lower yields. The biotransformation of testosterone by F. fujikuroi and A. griseolla was also investigated in order to examine the influence of the ester group on the course of transformation. Androst-4-ene-3,17-dione was only identified in the biotransformation of testosterone by F. fujikuroi. The same product was observed in incubation of testosterone by A. griseolla, together with 14α-hydroxy testosterone in very low yield. Furthermore, time course study was also carried out in order to examine the formation of metabolites as a function of time, which was determined by HPLC. The structures of compounds were determined by their comprehensive spectroscopic analysis and comparison with literature data.

  3. Erythrocytosis Following Testosterone Therapy.

    PubMed

    Ohlander, Samuel J; Varghese, Bibin; Pastuszak, Alexander W

    2017-05-16

    A rapid increase in awareness of androgen deficiency has led to substantial increases in prescribing of testosterone therapy (TTh), with benefits of improvements in mood, libido, bone density, muscle mass, body composition, energy, and cognition. However, TTh can be limited by its side effects, particularly erythrocytosis. This review examines the literature on testosterone-induced erythrocytosis and polycythemia. To review the available literature on testosterone-induced erythrocytosis, discuss possible mechanisms for pathophysiology, determine the significance of formulation, and elucidate potential thromboembolic risk. A literature review was performed using PubMed for articles addressing TTh, erythrocytosis, and polycythemia. Mechanism, pharmacologic contribution, and risk of testosterone-induced erythrocytosis. For men undergoing TTh, the risk of developing erythrocytosis compared with controls is well established, with short-acting injectable formulations having the highest associated incidence. Potential mechanisms explaining the relation between TTh and erythrocytosis include the role of hepcidin, iron sequestration and turnover, erythropoietin production, bone marrow stimulation, and genetic factors. High blood viscosity increases the risk for potential vascular complications involving the coronary, cerebrovascular, and peripheral vascular circulations, although there is limited evidence supporting a relation between TTh and vascular complications. Short-acting injectable testosterone is associated with greater risk of erythrocytosis compared with other formulations. The mechanism of the pathophysiology and its role on thromboembolic events remain unclear, although some data support an increased risk of cardiovascular events resulting from testosterone-induced erythrocytosis. Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sex Med Rev 2017;X:XXX-XXX. Copyright © 2017 International Society for Sexual Medicine

  4. Compounded Testosterone Troches TO OPTIMIZE HEALTH AND THE TESTOSTERONE CONTROVERSY.

    PubMed

    Guth, Michael A S

    2015-01-01

    As men age, testosterone levels progressively fall and inflammatory biomarkers increase. The gradual decline in testosterone production with aging, known as andropause, is common and may have deleterious effects on men including decreased overall well-being, increased sarcopenia, increased risk of cardiovascular disease, reduced sexual function, and bone loss. Therefore, it comes as no surprise that an increasing number of men worldwide have begun requesting testosterone replacement therapy from their physicians. Occasionally, physicians discourage male patients from getting testosterone replacement therapy based on a few recent studies indicating the therapy causes cardiovascular events, including myocardial infarctions. Yet, an extensive review of the testosterone replacement therapy literature reveals that the majority of clinical studies show that properly administered testosterone replacement therapy, in which estradiol and dihydrotestosterone levels are also controlled, has no adverse effects on myocardial infarction risk. The current state-of-the-art in testosterone replacement therapy comprises compounded testosterone troches; an aromatase inhibitor, such as generic Anastrazole, to control estradiol levels; and a 5α-reductase inhibitor, such as beneric Dutasteride or Finasteride, to control dihydrotestosterone. Compounded testosterone troches easily raise serum testosterone levels to the optimal range, are highly cost effective at $82 for a 180-day supply, and provide affordable access to testosterone replacement therapy to millions of men requesting it. Yet, the Blue Cross Blue Shield-associated firms have largely denied requests for coverage of compounded medications, including testosterone troches. Despite data demonstrating strong links between testosterone deficiency and significant comorbid conditions (including Type 2 diabetes and other metabolic syndrome diseases) as well as the health benefits of testosterone replacement therapy, some physian have

  5. Testosterone and other anabolic steroids as cardiovascular drugs.

    PubMed

    Shapiro, J; Christiana, J; Frishman, W H

    1999-05-01

    There has been much interest in the effect of sex hormones on cardiovascular risk factors and as a therapeutic modality in both men and women. In this article, testosterone is considered as a possible therapy for cardiovascular disease. It has been shown that the level of serum testosterone decreases in men as they age. Healthy men with low testosterone levels have increased cardiovascular risk factors, including high fasting and 2-hour plasma glucose, serum triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol, and apo A-I lipoprotein. Injections of testosterone to raise the levels to midnormal range have been shown to decrease total cholesterol and LDL cholesterol, while increasing high-density lipoprotein (HDL) cholesterol. Testosterone affects the clotting system by increasing thromboxane A (2) receptor activity and platelet aggregability. Testosterone has also been shown to augment the fibrinolytic system and antithrombin III activity. In men, testosterone has been shown to have antianginal effects, and endogenous levels have an inverse relationship to systolic blood pressure. Testosterone can be given in oral, injectable, pellet, and transdermal patch forms. There may be a role in administering testosterone to return men to normal physiologic range who have low serum levels. This treatment increases the risk of prostatic cancer, benign prostatism, erythrocytosis, and edema. No long-term studies of the effects of long-term testosterone replacement have been undertaken, so it is difficult to recommend this treatment as yet, but it is being considered as a therapy for augmenting skeletal muscle strength in patients with congestive heart failure.

  6. Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study.

    PubMed

    Jovanovic, Hristina; Kocoska-Maras, Ljiljana; Rådestad, Angelique Flöter; Halldin, Christer; Borg, Jacqueline; Hirschberg, Angelica Lindén; Nordström, Anna-Lena

    2015-02-01

    Sex hormones and the serotonergic system interact in the regulation of mood, learning, memory and sexual behaviour. However, the mechanisms have not been fully explored. The serotonin transporter protein (5-HTT) regulates synaptic concentrations of serotonin and is a primary target for selective serotonin reuptake inhibitors. The aim of this study was to explore how estrogen treatment alone or in combination with testosterone affects 5-HTT binding potentials measured by positron emission tomography (PET) in specific brain regions of postmenopausal women. Ten healthy surgically postmenopausal women (years since oophorectomy 7.5 ± 4.0, mean ± SD) underwent PET examinations at baseline, after three months of estrogen treatment (transdermal estradiol 100 μg/24 hours) and after another three months of combined estrogen and testosterone (testosterone undecanoate 40 mg daily) treatment using the radioligand [(11)C] MADAM developed for examination of the serotonin transporter. The 5-HTT binding potentials decreased significantly in several cortical regions, as well as in limbic and striatal regions after both estrogen treatment alone and combined estrogen/testosterone treatment in comparison to baseline. The observed decrease in 5-HTT could either be due to direct effects on serotonin transporter expression or be the result of indirect adaptation to estrogen and /or testosterone effects on synaptic serotonin levels. Although the mechanism still needs further exploration, the study supports the view that gonadal hormones play a role in serotonin regulated mood disorders.

  7. Melamine negatively affects testosterone synthesis in mice.

    PubMed

    Sun, Jiarui; Cao, Yinan; Zhang, Xinchen; Zhao, Qiling; Bao, Endong; Lv, Yingjun

    2016-12-01

    Several studies have found that melamine causes damage to the testes, epididymis and sperm. However, few studies have investigated the effect of melamine on the synthesis of testosterone, which plays an import role in testicular development and spermatogenesis. In present study, mice were orally administrated with 2, 10 or 50mg/kg of melamine for 28days. In these groups, various abnormalities were observed including disruption of the seminiferous tubule structure, an increased necrotic germ cells and sperm abnormalities, and a reduced sperm count. Melamine exposure also decreased the level of serum testosterone and levels of testicular StAR, P450scc and 17β-HSD. In addition, melamine exposure reduced the number of Leydig cells. Taken together, these results indicate that melamine exposure reduces the level of testosterone through down-regulation of StAR and testosterone synthetic enzyme expression and also a decreased number of Leydig cells. This may further affect testicular development and lead to sperm damage.

  8. Testosterone treatment in elderly men.

    PubMed

    Srinivas-Shankar, U; Sharma, D

    2009-01-01

    Testosterone has been used in testicular and hypothalamo-pituitary diseases since the 1940s. There is growing interest in the use of testosterone in aging men, and this has stimulated research into the benefits of male hormone replacement. Testosterone treatment of men with hypogonadism might have beneficial effects on body composition, muscle strength, sexual function, and cognition. There are several modes of administration of the male hormone, with injectable testosterone esters and implanted testosterone pellets being the mainstay of treatment until recently. These preparations are increasingly being replaced by transdermal patches, gels, and long-acting parenteral preparations. Testosterone patches and gels are ideally for elderly men. Treatment with the male hormone is relatively safe, if patients are selected appropriately and monitored carefully. The most important adverse effects are on the prostate. In this review, we briefly discuss the indications, contraindications, and benefits of testosterone treatment. Further, we list the adverse effects, advantages, and disadvantages of various testosterone preparations in elderly men.

  9. Could you have low testosterone?

    MedlinePlus

    Male menopause; Andropause; Testosterone deficiency; Androgen deficiency of the aging male; Late-onset hypogonadism ... Testosterone makes a man look and feel like a man. In a man, this hormone helps: Keep ...

  10. Testosterone and Men's Marriages.

    ERIC Educational Resources Information Center

    Booth, Alan; Dabbs, James M., Jr.

    1993-01-01

    Among 4,462 former servicemen surveyed, testosterone levels were positively related to not marrying and marital instability, and negatively related to every aspect of marital quality examined. Findings are analyzed in relation to three sociological theories of marital success based on socioeconomic status (educational attainment, income, and…

  11. Testosterone and Men's Marriages.

    ERIC Educational Resources Information Center

    Booth, Alan; Dabbs, James M., Jr.

    1993-01-01

    Among 4,462 former servicemen surveyed, testosterone levels were positively related to not marrying and marital instability, and negatively related to every aspect of marital quality examined. Findings are analyzed in relation to three sociological theories of marital success based on socioeconomic status (educational attainment, income, and…

  12. Metabolic studies of 1-testosterone in horses.

    PubMed

    Kwok, W H; Ho, Emmie N M; Leung, Gary N W; Tang, Francis P W; Wan, Terence S M; Wong, Henry N C; Yeung, John H K

    2013-02-01

    1-Testosterone (17β-hydroxy-5α-androst-1-en-3-one), a synthetic anabolic steroid, has been described as one of the most effective muscle-building supplements currently on the market. It has an anabolic potency of 200 as compared to 26 for testosterone. Apart from its abuse in human sports, it can also be a doping agent in racehorses. Metabolic studies on 1-testosterone have only been reported for human in the early seventies, whereas little is known about its metabolic fate in horses. This paper describes the studies of in vitro and in vivo metabolism of 1-testosterone in horses, with the aim of identifying the most appropriate target metabolites to be monitored for controlling the misuse or abuse of 1-testosterone in racehorses. Six in vitro metabolites, namely 5α-androst-1-ene-3α,17β-diol (T1a), 5α-androstane-3β,17β-diol (T2), epiandrosterone (T3), 16,17-dihydroxy-5α-androst-1-ene-3-one (T4 & T5), and 5α-androst-1-ene-3,17-dione (T6), were identified. For the in vivo studies, two thoroughbred geldings were each administered orally with 800 mg of 1-testosterone by stomach tubing. The results revealed that the parent drug and eight metabolites were detected in urine. Besides the four in vitro metabolites (T1a, T2, T3, and T5), four other urinary metabolites, namely 5α-androst-1-ene-3β,17α-diol (T1b), 5α-androst-1-ene-3β,17β-diol (T1c), 5α-androstane-3α,17α-diol (T7) and 5α-androstane-3β,17α-diol (T8) were identified. This study shows that the detection of 1-testosterone administration is best achieved by monitoring the parent drug, which could be detected for up to 30 h post-administration. Copyright © 2012 John Wiley & Sons, Ltd.

  13. Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum.

    PubMed

    Kuhnz, W; Baumann, A; Staks, T; Dibbelt, L; Knuppen, R; Jütting, G

    1993-10-01

    The pharmacokinetics of gestodene (GEST) and ethinylestradiol (EE2) were determined in 14 healthy women (age 18 to 32 years) during a treatment period of three months with a new tri-step combination oral contraceptive (Milvane). Prior to this treatment period, the same women received a single administration of a coated tablet containing 0.1 mg GEST together with 0.03 mg EE2. There was a wash-out phase of one week between both treatments. Following single dose administration, a mean terminal half-life of 18 h was observed for GEST. The total clearance was 0.9 ml x min-1 x kg-1 and the volume of distribution was 84 l. During a treatment cycle, GEST levels in the serum accumulated by a factor of 8 as compared to single dose administration. Steady-state drug levels were reached during the second half of each cycle. As compared to single dose administration, the following changes were observed for GEST at the end of treatment cycles one and three: prolonged terminal half-life (20 to 22 h), reduced total (0.16 ml x min-1 x kg-1) and free clearance (ca. 27 ml x min-1 x kg-1), reduced volume of distribution (ca. 18 l). A concomitant EE2-induced increase in the SHBG concentrations by a factor of three as compared to pretreatment values was observed during a treatment cycle and appeared to be mainly responsible for the changes in the pharmacokinetics of GEST. Marked changes were also seen for the serum protein binding of GEST. After single dose administration, the free fraction of GEST was 1.3% and the fractions bound to SHBG and albumin were 69.4% and 29.3%, respectively. At the end of cycle one, the free fraction was only 0.6% and the fractions bound to SHBG and albumin were 81.4% and 18.0%, respectively. There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of GEST at the end of cycles one and three. On the last day of treatment cycles one and three, the AUC(0-4h) values of EE2 were 299.2 and 278.1 pg x ml-1 x h, respectively

  14. An Overview of Testosterone Therapy.

    PubMed

    Lee, O Danny; Tillman, Ken

    2016-01-01

    Millions of men, as a result of the natural aging process, injury, illness, and medical therapies, experience a decline in testosterone levels that necessitate a need for testosterone supplementation therapy (TST). The signs and symptoms of testosterone decline may occur gradually, and low testosterone levels may be misdiagnosed as other medical conditions. Over the past two decades, there has been an increase in testing of testosterone levels and the use of TST. With so many men now on TST, it is essential for health care professionals to know the signs and symptoms, the causes of testosterone decline, how testosterone deficiency is diagnosed, what pathological changes are associated with testosterone decline, and the benefits and risks of TST. In addition, health care providers need to be aware of the various forms of testosterone available as well as the advantages and disadvantages of each. This article provides a brief overview of testosterone deficiency, TST treatment options and guidelines, and the risks and benefits associated with of TST.

  15. Controversies in testosterone replacement therapy: testosterone and cardiovascular disease.

    PubMed

    Hwang, Kathleen; Miner, Martin

    2015-01-01

    The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism.

  16. Prenatal testosterone and stuttering.

    PubMed

    Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin

    2015-01-01

    The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study.

    PubMed

    Hackett, Geoffrey; Cole, Nigel; Bhartia, Mithun; Kennedy, David; Raju, Jessie; Wilkinson, Peter

    2014-03-01

    The association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established and current endocrine society guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes or erectile dysfunction. We report the first double-blind, placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess metabolic changes with long-acting testosterone undecanoate (TU). The type 2 diabetes registers of seven general practices identified 211 patients for a 30-week double-blind, placebo-controlled study of long-acting TU 1,000 mg followed by 52 weeks of open-label use. Because of the established impact of age, obesity, and depression on sexual function, these variables were also assessed for influence on metabolic parameters. Changes in glycated hemoglobin (HbA1c) and the level of testosterone at which response are achieved. Treatment with TU produced a statistically significant reduction in HbA1c at 6 and 18 weeks and after a further 52 weeks of open-label medication most marked in poorly controlled patients with baseline HbA1c greater than 7.5 where the reduction was 0.41% within 6 weeks, and a further 0.46% after 52 weeks of open-label use. There was significant reduction in waist circumference, weight, and body mass index in men without depression, and improvements were related to achieving adequate serum levels of testosterone. There were no significant safety issues. Testosterone replacement therapy significantly improved HbA1c, total cholesterol, and waist circumference in men with type 2 diabetes. Improvements were less marked in men with depression at baseline, and therapeutic responses were related to achieving adequate serum testosterone levels. Current advice on 3- to 6-month trials of therapy may be insufficient to achieve maximal response. Patients reported significant improvements in general health. © 2013 International Society for Sexual Medicine.

  18. Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: a pharmacodynamic and pharmacokinetic study

    PubMed Central

    Wiehle, Ronald; Cunningham, Glenn R; Pitteloud, Nelly; Wike, Jenny; Hsu, Kuang; Fontenot, Gregory K; Rosner, Michele; Dwyer, Andrew; Podolski, Joseph

    2013-01-01

    Objectives To determine the pharmacodynamic profile of serum total testosterone and luteinizing hormone (LH) levels in men with secondary hypogonadism after initial and chronic daily oral doses of enclomiphene citrate vs transdermal testosterone. To determine the effects of daily oral doses of enclomiphene citrate in comparison with transdermal testosterone on other hormones and markers in men with secondary hypogonadism. Patients and Methods This was a randomized, single-blind, two-centre, phase II study to evaluate the effects of three different doses of enclomiphene citrate (6.25, 12.5 and 25 mg) vs transdermal testosterone on 24-h LH and total testosterone in otherwise normal healthy men with secondary hypogonadism. Forty-eight men were enrolled in the trial (the intent-to-treat population), but four men had testosterone levels >350 ng/dL at baseline. Forty-four men completed the study per protocol. All subjects enrolled in this trial had serum total testosterone in the low range (<350 ng/dL) and had low to normal LH (<12 IU/L) on at least two occasions. Total testosterone and LH levels were assessed each hour for 24 h to examine the effects at each of three treatment doses of enclomiphene citrate vs a standard dose (5 g) of transdermal testosterone. In the initial profile, total testosterone and LH were determined in a naïve population after a single initial oral or transdermal treatment (day 1). This was contrasted to that seen after 6 weeks of continuous daily oral or transdermal treatment (day 42). The pharmacokinetics of enclomiphene citrate were assessed in a select subpopulation. Serum samples were obtained over the course of the study to determine the levels of various hormones and lipids. Results After 6 weeks of continuous use, the mean (sd) concentration of total testosterone at day 42 was 604 (160) ng/dL for men taking the highest dose of enclomiphene citrate (enclomiphene citrate, 25 mg daily) and 500 (278) ng in those men treated with transdermal

  19. Testosterone Therapy and Prostate Cancer.

    PubMed

    Davidson, Emily; Morgentaler, Abraham

    2016-05-01

    Changes in understanding regarding the relationship of androgens and prostate cancer have led to changes in the use of testosterone therapy. The evidence supports a finite ability of androgens to stimulate prostate cancer growth, with a maximum achieved at low testosterone concentrations, called the saturation model. The saturation point corresponds with maximal androgenic stimulation at 250 ng/dL. Evidence is reviewed herein regarding the relationship of testosterone to prostate cancer and the relatively new practice of offering testosterone therapy to men with a history of prostate cancer. Although no prospective controlled trials have been performed, results have been reassuring.

  20. Investigations into the separation behaviour of perfluorinated C8 and undecanoic acid modified silica hydride stationary phases.

    PubMed

    Kulsing, Chadin; Yang, Yuanzhong; Sepehrifar, Roshanak; Lim, Michael; Toppete, Joshua; Matyska, Maria T; Pesek, Joseph J; Boysen, Reinhard I; Hearn, Milton T W

    2016-04-15

    In this study, the surface charge properties of perfluorinated C8 (PerfluoroC8) and undecanoic acid (UDA) modified silica hydride stationary phases have been investigated. The zeta potential values of these stationary phases were measured in aqueous/acetonitrile mobile phases of different pH, buffer concentrations and acetonitrile contents. The retention behaviour of several basic, acidic and neutral compounds were then examined with these two stationary phases, with U-shaped retention dependencies evident with regard to the organic solvent content of the mobile phase. Plots of the logarithmic retention factor versus buffer concentration revealed slopes ≥ -0.41 for both stationary phases, indicating the involvement of mixed mode retention mechanisms with contributions from both ionic and non-ionic interactions. Using a linear solvation energy relationship approach, the origins of these interactions under different mobile phase conditions were differentiated and quantified. The PerfluoroC8 stationary phase exhibited stronger retention for basic compounds under high acetonitrile content mobile phase conditions, whilst stronger retention was observed for all compounds with the UDA stationary phase under high aqueous content mobile phase conditions. The more negative zeta potentials of the UDA stationary phase correlated with higher total charge density, surface charge density and charge density at the beta plane (the outer plane of the double layer) compared to the PerfluoroC8 stationary phase. With mobile phases of low buffer concentrations, more negative zeta potential values were unexpectedly observed for the PerfluoroC8 stationary phase with slight increases in the C descriptor value, reflecting also the greater accessibility of the analytes to the stationary phase surface. Comparison of the retention behaviours on these phases with other types of silica hydride stationary phases has revealed different patterns of selectivity. Copyright © 2016 Elsevier B

  1. Testosterone Lab Testing and Initiation in the United Kingdom and the United States, 2000 to 2011

    PubMed Central

    Li, Dongmei; Meier, Christoph R.; Sharpless, Julie L.; Stürmer, Til; Jick, Susan S.; Brookhart, M. Alan

    2014-01-01

    Context: New formulations, increased marketing, and wider recognition of declining testosterone levels in older age may have contributed to wider testosterone testing and supplementation in many countries. Objective: Our objective was to describe testosterone testing and testosterone treatment in men in the United Kingdom and United States. Design: This was a retrospective incident user cohort. Setting: We evaluated commercial and Medicare insurance claims from the United States and general practitioner healthcare records from the United Kingdom for the years 2000 through 2011. Participants: We identified 410 019 US men and 6858 UK men who initiated a testosterone formulation as well as 1 114 329 US men and 66 140 UK men with a new testosterone laboratory measurement. Main Outcome Measures: Outcome measures included initiation of any injected testosterone, implanted testosterone pellets, or prescribed transdermal or oral testosterone formulation. Results: Testosterone testing and supplementation have increased pronouncedly in the United States. Increased testing in the United Kingdom has identified more men with low levels, yet US testing has increased among men with normal levels. Men in the United States tend to initiate at normal levels more often than in the United Kingdom, and many men initiate testosterone without recent testing. Gels have become the most common initial treatment in both countries. Conclusions: Testosterone testing and use has increased over the past decade, particularly in the United States, with dramatic shifts from injections to gels. Substantial use is seen in men without recent testing and in US men with normal levels. Given widening use despite safety and efficacy questions, prescribers must consider the medical necessity of testosterone before initiation. PMID:24423353

  2. [The method of tonifying kidneys and activating blood circulation increases testosterone secretion index in late-onset hypogonadism males with kidney deficiency].

    PubMed

    Zhou, Shao-Hu; Weng, Zhi-Wei; Li, Tang-Lin

    2013-07-01

    To investigate the effect of the method of tonifying the kidney and activating blood circulation on the testosterone secretion index (TSI) in late-onset hypogonadism (LOH) male patients with kidney deficiency and its possible mechanisms. We screened 60 LOH male patients with kidney deficiency based on the scores on Partial Androgen Deficiency in Aging Males (PADAM), the levels of serum total testosterone (TT) and luteinizing hormone (LH), and TSI (TT/LH). We randomly divided the patients into a Nan Geng Ning (NGN) group (n = 40, aged 55.02 +/- 11.37 years) and a control group (n = 20, aged 54.56 +/- 12.12 years) to be treated orally with NGN decoction and testosterone undecanoate capsules, respectively, both for 12 consecutive weeks. We obtained the scores on psychological status, physical status and sexual function and observed the changes in serum TT, LH and TSI after 4, 8 and 12 weeks of treatment. Compared with the baseline, both the NGN and control groups showed a significant reduction after 12 weeks of medication in the LH level ([5.32 +/- 2.08] vs [4.89 +/- 1.46] IU/L and [5.36 +/- 2.07] vs [4.81 +/- 1.75] IU/L, P < 0.05), psychological status score (5.2 +/- 1.3 vs 2.7 +/- 1.4 and 4.8 +/- 2.2 vs 2.9 +/- 1.2, P < 0.05), physical status score (6.9 +/- 2.5 vs 2.9 +/- 1.6 and 7.1 +/- 2.7 vs 3.1 +/- 1.5, P < 0.05) and sexual function score (10.2 +/- 3.3 vs 4.5 +/- 2.9 and 9.8 +/- 3.1 vs 4.8 +/- 3.0, P < 0.05), but a remarkable increase in the TT level ([11.13 +/- 0.69] vs [14.55 +/- 0.75] nmol/L and [10.99 +/- 0.74] vs [14.74 +/- 0.83] nmol/L, P < 0.05) and TSI ([2.14 +/- 0.65] vs [2.99 +/- 0.72] nmol/IU and ([2.05 +/- 0.73] vs [3.11 +/- 0.65] nmol/IU, P < 0.05). However, no significant differences were found between the NGN and control groups at 12 weeks in LH ([4.89 +/- 1.46] vs [4.81 +/- 1.75] IU/L, P > 0.05), TT ([14.55 +/- 0.75] vs [14.74 +/- 0.83] nmol/L, P > 0.05), TSI ([2.99 +/- 0.72] vs [3.11 +/- 0.65] nmol/IU, P > 0.05), psychological status score (2

  3. Testosterone and metabolic syndrome.

    PubMed

    Cunningham, Glenn R

    2015-01-01

    Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  4. Testosterone and metabolic syndrome

    PubMed Central

    Cunningham, Glenn R

    2015-01-01

    Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels. PMID:25652634

  5. Significant increase of salivary testosterone levels after single therapeutic transdermal administration of testosterone: suitability as a potential screening parameter in doping control.

    PubMed

    Thieme, Detlef; Rautenberg, Claudia; Grosse, Joachim; Schoenfelder, Martin

    2013-01-01

    The legally defensible proof of the abuse of endogenous steroids in sports is currently based on carbon isotope ratio mass spectrometry (IRMS), i.e. a comparison between (13)C/(12)C ratios of diagnostic precursors and metabolites of testosterone. The application of this technique requires a chromatographic baseline separation of respective steroids prior to IRMS detection and hence laborious sample pre-processing of the urinary steroid extracts including clean up by solid-phase extraction and/or liquid chromatography. Consequently, an efficient pre-selection of suspicious control urine samples is essential for appropriate follow up confirmation by IRMS and effective doping control. Two single transdermal administration studies of testosterone (50 mg Testogel® and Testopatch® at 3.8 mg in 16 h, respectively) were conducted and resulting profiles of salivary testosterone and urinary steroid profiles and corresponding carbon isotope ratios were determined. Conventional doping control markers (testosterone/epitestosterone ratio, threshold concentrations of androsterone, etiocholanolone, or androstanediols) did not approach or exceed critical thresholds. In contrast to these moderate variations, the testosterone concentration in oral fluid increased from basal values (30-142 pg/mg) to peak concentrations above 1000 pg/mg. It is likely that this significant increase in oral fluid is due to a pulsatile elevation of free (protein unbound) circulating testosterone after transdermal administration and may be assumed to represent a more diagnostic marker for transdermal testosterone administration.

  6. A clinical update on female androgen insufficiency--testosterone testing and treatment in women presenting with low sexual desire.

    PubMed

    Burger, Henry G; Papalia, Mary-Anne

    2006-05-01

    The diagnosis of female androgen deficiency syndrome is suggested by complaints of a diminished sense of well being, persistent unexplained fatigue and decreased sexual desire, sexual receptivity and pleasure in a woman who is oestrogen-replete and in whom no other significant contributing factors can be identified. The diagnosis is supported by the finding of low circulating concentrations of free testosterone. Barriers to its recognition include the non-specificity of the symptoms and methodological problems due to insensitive testosterone assays. Barriers to its treatment include the unavailability of satisfactory forms of testosterone for administration to women and lack of data regarding long-term safety. Although several conditions lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and use of oral contraceptives and oral oestrogens, it is important for clinicians to recognise that in normal women, androgen levels decline by 50% from the early 20s to the mid 40s, and hence age-related androgen insufficiency may occur in women in their late 30s and 40s, as well as postmenopausally. Satisfactory measurements of free testosterone requires a sensitive and reliable assay for total testosterone, and quantitation of sex hormone binding globulin, from which free testosterone is readily calculated. Adverse effects of testosterone treatment are few if replacement is monitored to achieve physiological circulating testosterone concentrations. Currently, available methods include testosterone implants and testosterone creams, and transdermal patches and sprays are in development.

  7. Testosterone therapy in erectile dysfunction.

    PubMed

    Shabsigh, R

    2004-12-01

    Studies in animals have indicated that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction and a reduction in nitric oxide synthase-stained nerves in erectile tissue. Furthermore, castration adversely affects penile hemodynamics and smooth muscle content, leading to veno-occlusive dysfunction. Testosterone replenishment reverses these physiological, biochemical and structural changes. Several clinical studies have demonstrated the benefits of a combination of testosterone and sildenafil. A recently published, multicenter study evaluated the safety and efficacy of testosterone gel 1% (Testogel; Schering AG, Germany/AndroGel; Solvay Pharmaceuticals) vs. placebo gel in conjunction with sildenafil, in producing an erectile response in hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. The selection criteria required subjects to have had erectile dysfunction for at least 3 months, to be non-responsive to 100 mg sildenafil and to have low testosterone levels (< 400 ng/dl). The primary efficacy measurement was the mean change from baseline in the Erectile Function domain of the International Index of Erectile Function (IIEF). Secondary outcome measures included the mean change from baseline in the other domains and the total sum of the IIEF. Subjects were randomized to receive either testosterone gel + sildenafil, or placebo gel + sildenafil for 12 weeks. Testosterone therapy with testosterone gel improved the erectile response to sildenafil. Therefore, testosterone therapy may be considered for the treatment of erectile dysfunction in men with low to low-normal testosterone levels, who have failed prior treatment with sildenafil alone. Consequently, it is important to screen for hypogonadism in men who fail PDE5 inhibitors.

  8. Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

    PubMed

    Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

    2011-07-01

    Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older

  9. Effects of chrysin on urinary testosterone levels in human males.

    PubMed

    Gambelunghe, Cristiana; Rossi, Ruggero; Sommavilla, Marco; Ferranti, Chiara; Rossi, Riccardo; Ciculi, Chiara; Gizzi, Stefania; Micheletti, Alessandra; Rufini, Stefano

    2003-01-01

    The equilibrium of sexual hormones in both sexes is controlled in vertebrates by the enzyme aromatase, a member of the cytochrome P450 superfamily, which catalyzes the conversion of androstenedione and testosterone into estrone and estradiol, respectively. Flavonoids are diphenolic compounds present in whole grains, legumes, fruits, and vegetables that are strongly implicated as protective in coronary heart disease, stroke, and cancer. One flavonoid, chrysin, found in high concentrations in honey and propolis, has been shown to be an inhibitor of aromatase enzyme activity. These foods are often used as supplements, particulary by sportsmen for their energetic and antioxidant properties. The aim of this study was to verify if daily treatment for 21 days with propolis and honey, containing chrysin, would modify urinary concentrations of testosterone in volunteer male subjects. In fact, aromatase inhibition by chrysin could block the conversion of androgens into estrogens with a consequent increase of testosterone, eventually measurable in urine samples. The obtained data did not show alterations of the levels of testosterone in the volunteers after 7, 14, and 21 days of treatment in comparison with baseline values and compared with measurements on the control subjects at the same time. In conclusion, the use of these foods for 21 days at the doses usually taken as oral supplementation does not have effects on the equilibrium of testosterone in human males.

  10. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments...

  11. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments...

  12. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments...

  13. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments...

  14. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments...

  15. The ball's in your court: testosterone 101.

    PubMed

    Horn, T; Cooper, S

    1997-11-01

    Testosterone, a hormone, plays several important functions in nutrition, libido, and the development of masculine traits. Studies have shown that testosterone levels in both men and women with HIV and AIDS are generally very low. The definition of normal testosterone is broad and determining when a person has low levels is difficult since individuals have different testosterone baselines. Testosterone replacement therapy, available for men but not for women yet, is used to increase body mass and prevent wasting. Testosterone is available in several forms, including a patch, and the advantages of each form are discussed. Testosterone level tests are readily available and are generally covered by insurance and Medicaid.

  16. The role of testosterone therapy in postmenopausal women: position statement of The North American Menopause Society.

    PubMed

    2005-01-01

    To create an evidence-based position statement regarding the role of exogenous testosterone in postmenopausal women. The North American Menopause Society (NAMS) enlisted a panel of clinicians and researchers acknowledged to be experts in the field of testosterone therapy to review the evidence obtained from the medical literature, compile supporting statements and conclusions, and reach consensus on recommendations. The document was reviewed and approved by the NAMS Board of Trustees. Endogenous testosterone levels have not been clearly linked to sexual function in postmenopausal women. Published evidence from randomized controlled trials, although limited, indicates that exogenous testosterone, both oral and nonoral formulations, has a positive effect on sexual function, primarily desire, arousal, and orgasmic response, in women after spontaneous or surgically induced menopause. Data are inadequate to support recommending testosterone use for any other indication, including preserving or increasing bone mineral density, reducing hot flashes, increasing lean body mass, or improving well-being. Hirsutism and acne have been associated with testosterone therapy, but the actual risks are not well defined. It is not known whether testosterone therapy increases the risk of breast cancer, cardiovascular disease, or thromboembolic events. There are few data regarding the safety and efficacy of testosterone therapy in women not using concomitant estrogen therapy or for the use of testosterone therapy for longer than 6 months. Clinically available laboratory assays do not accurately detect testosterone concentrations at the values typically found in women, and no testosterone level has been clearly linked to a clinical syndrome of hypoandrogenism or testosterone insufficiency. Postmenopausal women with decreased sexual desire associated with personal distress and with no other identifiable cause may be candidates for testosterone therapy. Testosterone treatment without

  17. A case of hyperpigmentation and acanthosis nigricans by testosterone injections.

    PubMed

    Karadag, As; Kavala, M; Demir, Ft; Turkoğlu, Z; Kartal, I; Zemheri, E

    2014-12-01

    Drug-related skin disorders may occur in many different ways. Despite pigmentary changes being less important for morbidity, these changes precipitate depressed mood and reduce self-confidence. Testosterone is a steroid hormone from the androgen group and primarily used for the treatment of hypogonadism in males. Testosterone replacement can cause skin problems like acne, hair loss, redness, pain, or infection at the injection site. The study was conducted on a 49-year-old man with adult onset idiopathic hypogonadotropic hypogonadism, which is an acquired form of isolated gonadotropin-releasing hormone deficiency. He was presented with lack of energy and decreased sexual function 10 years ago and was given an oil-based injectable blend of four esterized testosterone compounds as hormone replacement treatment in a urology polyclinic. He was referred to our polyclinic by endocrinologist because of progressive hyperpigmentation marked on his face and oral mucosa. In the present study, we report the first testosterone therapy-related facial and oral mucosal hyperpigmentation and acanthosis nigricans in the same patient. © The Author(s) 2014.

  18. Controversies in testosterone replacement therapy: testosterone and cardiovascular disease

    PubMed Central

    Hwang, Kathleen; Miner, Martin

    2015-01-01

    The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism. PMID:25652628

  19. Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters.

    PubMed

    Yassin, Aksam; Nettleship, Joanne E; Talib, Raidh A; Almehmadi, Yousef; Doros, Gheorge

    2016-01-01

    Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function - erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.

  20. Estrogen, testosterone, and gender differences.

    PubMed

    Dluzen, Dean E

    2005-08-01

    The purpose of this report is to gain some current perspective on the definition, bases, and trends for research associated with gender differences. To accomplish this goal an analysis on the number of citations from a 1994-2004 Medline search with the terms estrogen, testosterone, gender differences, sex differences as well as the combinations of these terms was performed. Other combinations of terms included separate searches of estrogen, testosterone, and their combination within males or females, and an analysis of gender and sex differences with the terms human and animal. The salient results from this survey include: (1) An overall greater ratio of estrogen:testosterone citations when these terms were searched alone or in combination with gender differences; (2) an overall greater ratio of testosterone:estrogen citations when these terms were combined with sex differences or conducted separately within males or females, although this trend was shifting toward decreased testosterone and increased estrogen citation numbers toward the latter years of the survey; (3) a trend for increasing numbers of estrogen and gender differences citations over the period of the survey; (4) a clear indication for the term gender differences to be associated with the search term human; and (5) a very small number of citations when the terms estrogen and testosterone were combined. Interpretations and implications of these results are discussed.

  1. Lower urinary tract symptoms improve with testosterone replacement therapy in men with late-onset hypogonadism: 5-year prospective, observational and longitudinal registry study.

    PubMed

    Yassin, Dany-Jan; El Douaihy, Yousef; Yassin, Aksam A; Kashanian, James; Shabsigh, Ridwan; Hammerer, Peter G

    2014-08-01

    Many men with "late-onset hypogonadism" (LOH) experience lower urinary tract symptoms (LUTS) that can be distressing and may decrease quality of life. LUTS often appear in men when testosterone levels begin to decline, which could be a significant association. We investigated whether testosterone replacement could alleviate LUTS in men with LOH. Two hundred and sixty-one hypogonadal patients (mean age 59.5 years) presenting with erectile dysfunction, having also been evaluated for LUTS, received a single testosterone undecanoate injection at day 1, at week 6 and quarterly thereafter. Parameters, including International Prostate Symptom Score (IPSS), post-voiding residual urine volume, transrectal ultrasound, prostate volume and prostate-specific antigen were measured at each treatment visit. Two hundred and fifty-nine patients were included in the full analysis set. These were subsequently divided into weight losers (L ≥ 5 % weight loss at last visit from baseline) and non-losers (NL). t test analyses were used to compare the IPSS means of these subgroups. The potentially confounding effect on IPSS of using the phosphodiesterase-5 inhibitor (PDE5i) vardenafil was also accounted for. Mean IPSS showed a significant decrease with time following initiation of testosterone treatment (p < 0.05). No significant differences were observed in either IPSS between L and NL groups or in mean IPSS between vardenafil users and non-users. Testosterone replacement is associated with improvements in LUTS which are not confounded by weight loss or PDE5i. The mechanisms of this association require further investigation.

  2. Fetal testosterone and empathy.

    PubMed

    Knickmeyer, Rebecca; Baron-Cohen, Simon; Raggatt, Peter; Taylor, Kevin; Hackett, Gerald

    2006-03-01

    In animals, fetal testosterone (fT) plays a central role in organizing the brain and in later social behavior. In humans, exposure to atypical levels of prenatal androgens may result in masculine behavior and ability patterns. Normal inter-individual variation in fT levels has also been correlated with later sex-typed behavior. In the current study, 38 children (24 male, 14 female), whose fT was analyzed in amniotic fluid, were followed up at age 4. They were asked to describe cartoons with 2 moving triangles whose interactions with each other suggested social relationships and psychological motivations. Females used more mental and affective state terms to describe the cartoons than males. fT was not associated with the frequency of mental or affective state terms. Females also used more intentional propositions than males. fT was negatively correlated with the frequency of intentional propositions, taking sex differences into account. fT was also negatively correlated with the frequency of intentional propositions when males were examined separately. Males used more neutral propositions than females. fT was directly correlated with the frequency of neutral propositions, taking sex differences into account. This relationship was not seen when males and females were examined separately. These findings implicate fT in human social development. The relevance of our findings to the 'extreme male brain' theory of autism is also discussed.

  3. Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadal elderly men: real-life experience from an observational registry study.

    PubMed

    Yassin, A A; Nettleship, J; Almehmadi, Y; Salman, M; Saad, F

    2016-09-01

    Subnormal levels of testosterone are associated with significant negative health consequences, with higher risks of all-cause and cardiovascular mortality. The numbers of studies reporting on the benefits of normalisation of testosterone is increasing but longer-term data on (elderly) men receiving testosterone treatment are almost nonexistent. In this single-centre, cumulative, prospective, registry study, 115 hypogonadal men (mean age 59.05 years) received injections with testosterone undecanoate in 12-week intervals for up to 10 years. Waist circumference, body weight and mean BMI dropped progressively with statistical significance versus previous year for 7 years and, respectively, 8 years for weight and body mass index. Similarly, fasting glucose displayed a significant decrease after the first year continuing to decrease thereafter. A decline in HbA1c , from 6.4% to 5.6% (mean <6%), was observed from year 2 on, together with a decrease in the ratio of triglycerides:high-density lipoprotein (HDL), a surrogate marker of insulin resistance, with an increase in HDL levels. The total cholesterol:HDL ratio and non-HDL cholesterol declined significantly. A decrease was also observed in systolic and diastolic blood pressure, with a decrease in levels of the inflammation marker C-reactive protein. No major adverse cardiovascular events were observed throughout the study.

  4. Testosterone, thrombophilia, thrombosis.

    PubMed

    Glueck, Charles J; Friedman, Joel; Hafeez, Ahsan; Hassan, Atif; Wang, Ping

    2014-10-01

    We assessed previously undiagnosed thrombophilia-hypofibrinolysis in 11 testosterone (T)-taking men, five of whom developed deep venous thrombosis (DVT), four pulmonary embolism, one spinal cord infarction, and one osteonecrosis 3.5 months (median) after starting T gel (50-160 mg/day) or T intramuscular (50-250 mg/week). In the order of referral because of thrombosis after starting T, thrombophilia-hypofibrinolysis was studied in 11 men, and, separately, in two control groups without thrombosis - 44 healthy normal male controls and 39 healthy men taking T. Nine men had DVT or DVT-pulmonary embolism after 3.5 months (median) on T, one spinal cord infarction after 5 days on T, and one had osteonecrosis (knee and then hip osteonecrosis after 6 and 18 months on T). Four of the 11 men (36%) had high factor VIII (≥150%) vs. one of 42 (2%) controls (P = 0.005), and vs. one of 25 (4%) T-controls, (P = 0.023). Of the 11 men, two (18%) had factor V Leiden heterozygosity vs. none of 44 controls, (P = 0.04) and vs. none of 39 T-controls(P = 0.045). Of the 11 men, three had 4G4G plasminogen activator inhibitor-1 homozygosity, one prothrombin G20210A heterozygosity, one low protein S, and one high factor XI. When T was continued, second DVT-pulmonary embolism recurred in three of 11 men despite adequate anticoagulation. T interacts with thrombophilia-hypofibrinolysis leading to thrombosis. Men sustaining DVT-pulmonary embolism-osteonecrosis on T should be studied for thrombophilia. Continuation of T in thrombophilic men appears to be contraindicated because of recurrent thrombosis despite adequate anticoagulation. Before starting T, to prevent T-associated thrombosis, we recommend measures of factor V Leiden, factor VIII, and the prothrombin gene.

  5. TESTOSTERONE AND SPORT: CURRENT PERSPECTIVES

    PubMed Central

    Wood, Ruth I.; Stanton, Steven J.

    2011-01-01

    Testosterone and other anabolic-androgenic steroids enhance athletic performance in men and women. As a result, exogenous androgen is banned from most competitive sports. However, due to variability in endogenous secretion, and similarities with exogenous testosterone, it has been challenging to establish allowable limits for testosterone in competition. Endogenous androgen production is dynamically regulated by both exercise and winning in competition. Furthermore, testosterone may promote athletic performance, not only through its long-term anabolic actions, but also through rapid effects on behavior. In women, excess production of endogenous testosterone due to inborn disorders of sexual development (DSD) may convey a competitive advantage. For many years, female competitors have been subject to tests of sexual genotype and phenotype known as gender verification. Although gender verification has not identified any normal man competing as a woman, this process has identified women athletes with DSD. As understanding of DSD has expanded in recent years, women with DSD are increasingly able to continue athletic competition. PMID:21983229

  6. Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone.

    PubMed

    Dias, Jenny Pena; Veldhuis, Johannes D; Carlson, Olga; Shardell, Michelle; Chia, Chee W; Melvin, Denise; Egan, Josephine M; Basaria, Shehzad

    2017-04-01

    Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men. This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone. Thirty-seven men, ≥65years with total testosterone <350ng/dL were randomized to 5g transdermal testosterone gel (TT), 1mg oral aromatase inhibitor (AI) or placebo daily for 12months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6months. At 3months, mean GH and in IGF-1 were similar between the three groups. At 6months, IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo (P=0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P=0.04; AI-group, P=0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P=0.0018) compared to placebo while it remained unchanged in the AI-group (P=0.059). In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Testosterone and weight loss: the evidence

    PubMed Central

    Traish, Abdulmaged M.

    2014-01-01

    Purpose of review The purpose of this article is to examine the contemporary data linking testosterone therapy in overweight and obese men with testosterone deficiency to increased lean body mass, decreased fat mass, improvement in overall body composition and sustained weight loss. This is of paramount importance because testosterone therapy in obese men with testosterone deficiency represents a novel and a timely therapeutic strategy for managing obesity in men with testosterone deficiency. Recent findings Long-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, marked reduction in waist circumference and BMI and improvement in body composition. Further, testosterone therapy ameliorates components of the metabolic syndrome. The aforementioned improvements are attributed to improved mitochondrial function, increased energy utilization, increased motivation and vigor resulting in improved cardio-metabolic function and enhanced physical activity. Summary The implication of testosterone therapy in management of obesity in men with testosterone deficiency is of paramount clinical significance, as it produces sustained weight loss without recidivism. On the contrary, alternative therapeutic approaches other than bariatric surgery failed to produce significant and sustained outcome and exhibit a high rate of recidivism. These findings represent strong foundations for testosterone therapy in obese men with testosterone deficiency and should spur clinical research for better understanding of usefulness of testosterone therapy in treatment of underlying pathophysiological conditions of obesity. PMID:25105998

  8. Testosterone, thrombophilia, thrombosis.

    PubMed

    Freedman, Joel; Glueck, Charles J; Prince, Marloe; Riaz, Rashid; Wang, Ping

    2015-05-01

    We screened previously undiagnosed thrombophilia (V Leiden-prothrombin mutations, Factors VIII and XI, homocysteine, and antiphospholipid antibody [APL] syndrome) in 15 men and 2 women with venous thromboembolism (VTE) or osteonecrosis 7 months (median) after starting testosterone therapy (TT), gel (30-50 mg/d), intramuscular (100-400 mg/wk), or human chorionic gonadotropin (HCG) (6000 IU/wk). Thrombophilia was studied in 2 healthy control groups without thrombosis (97 normal controls, 31 subjects on TT) and in a third control group (n = 22) with VTE, not on TT. Of the 17 cases, 76% had ≥1 thrombophilia vs 19% of 97 normal controls (P < 0.0001), vs 29% of 31 TT controls (P = 0.002). Cases differed from normal controls by Factor V Leiden (12% vs 0%, P = 0.021), by high Factor VIII (>150%) (24% vs 7%, P = 0.058), by high homocysteine (29% vs 5%, P = 0.007), and from both normal and TT controls for APL syndrome (18% vs 2%, P = 0.023, vs 0%, P = 0.04). Despite adequate anticoagulation with TT continued after the first deep venous thrombosis-pulmonary embolus (DVT-PE), 1 man sustained 3 DVT-PEs 5, 8, and 11 months later and a second man had 2 DVT-PEs 1 and 2 months later. Of the 10 cases with serum T measured on TT, 6 (60%) had supranormal T (>800 ng/dL) and of 9 with estradiol measured on TT, 7 (78%) had supranormal levels (>42.6 pg/mL). TT interacts with thrombophilia leading to thrombosis. TT continuation in thrombophilic men is contraindicated because of recurrent thrombi despite anticoagulation. Screening for thrombophilia before starting TT should identify subjects at high risk for VTE with an adverse the risk to benefit ratio for TT.

  9. Testosterone replacement therapy and prostate health.

    PubMed

    Polackwich, A Scott; Ostrowski, Kevin A; Hedges, Jason C

    2012-12-01

    There is an emerging evolution in the understanding of the relationship between the prostate and testosterone. It has long been generally believed that with testosterone replacement therapy (TRT), increasing serum testosterone levels led to prostatic growth and worsening of voiding dysfunction and associated complications. A new theory, the Saturation Model of Testosterone and its effect on the Prostate has gained attention. This theory suggests that the prostate's response to increasing levels of serum testosterone reaches a limit beyond which there is minimal effect. This model predicts that testosterone replacement therapy occurs above this saturation point, and replacing testosterone to eugonadal levels should not worsen prostate related benign disease. We evaluated the recent published data, with an emphasis on clinical studies done within the last 3 years, for the effects of testosterone supplementation on benign prostatic disease.

  10. TV Ads Help Drive Testosterone Supplement Sales

    MedlinePlus

    ... news/fullstory_164208.html TV Ads Help Drive Testosterone Supplement Sales Study found link between ads airing, ... TV ads have helped spur a boom in testosterone treatments, convincing many men that they need hormone ...

  11. Testosterone replacement in older men and women.

    PubMed

    Morley, J E

    2001-01-01

    This article examines in detail the present state of the art concerning androgen deficiency in aging males. There is increasing evidence that testosterone replacement in hypogonadal older males can result in an improvement in quality of life. The major effects of testosterone are on libido, muscles, bone, and cognition. Less information is available concerning the role of testosterone in postmenopausal women, but testosterone replacement may have a role to play in treating disorders of libido and the sarcopenia that occurs at menopause.

  12. Gender-Typed Play and Amniotic Testosterone

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

    2005-01-01

    Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

  13. Gender-Typed Play and Amniotic Testosterone

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

    2005-01-01

    Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

  14. Cortisol and testosterone increase financial risk taking and may destabilize markets

    PubMed Central

    Cueva, Carlos; Roberts, R. Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N.; Herbert, Joe; Rustichini, Aldo

    2015-01-01

    It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders’ financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways. PMID:26135946

  15. Cortisol and testosterone increase financial risk taking and may destabilize markets.

    PubMed

    Cueva, Carlos; Roberts, R Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N; Herbert, Joe; Rustichini, Aldo

    2015-07-02

    It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders' financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways.

  16. Effects of ciprofloxacin on testosterone and cortisol concentrations in healthy males.

    PubMed Central

    Waite, N M; Edwards, D J; Arnott, W S; Warbasse, L H

    1989-01-01

    Several inhibitors of oxidative drug metabolism inhibit the synthesis of endogenous compounds such as testosterone and cortisol. Since ciprofloxacin is a potent inhibitor of the metabolism of a number of drugs, we studied its effect on serum testosterone and cortisol concentrations in eight healthy male subjects. Blood samples were collected over a 12-h period under baseline conditions and following the first and final doses of ciprofloxacin (500 mg orally every 12 h for 4 days). No significant differences in concentrations or area under the concentration-time curve were found when baseline values were compared with those observed for either testosterone or cortisol after ciprofloxacin administration. These results suggest that ciprofloxacin is unlikely to have either antiandrogenic side effects or clinical utility in lowering testosterone or cortisol concentration. PMID:2610498

  17. [Testosterone and atherosclerosis in males during andropause].

    PubMed

    Medraś, M; Jankowska, E

    1999-04-01

    Nowadays besides the commonly accepted atherogenic risk factors a special emphasis is laid on the significance of testosterone in atherogenesis in men which physiologic deficit during "andropause" is able to promote this pathology. An elevated estradiol:testosterone ratio seems to be an independent risk factor of atheromatous heart complications. There is a proved positive correlation between free testosterone, total testosterone, dihydrotestosterone and HDL-cholesterol, apoA1 apolipoprotein. The relationship between LDL-cholesterol, VLDL-cholesterol, total cholesterol and total and free testosterone seems to be unanimous, but in certain studies the beneficial influence of testosterone on the mentioned lipids has been observed. The discussed hormone is also functionally connected with coagulation and fibrynolisis; a positive correlation was found between endogenous testosterone and tPA-Fx and a negative correlation between testosterone and PAI-1, fibrinogen, D-dimers, alpha 2-antiplasmin. Testosterone is a functional regulator of the vascular tonus and influences on reological properties of microcirculation (the application of testosterone infusion into canine coronary arteries causes the dilatation of main and the small vessels, through NO syntetase induction and ATP-dependent K(+)- channel activation). A statistically significant positive correlation between testosterone and insulin has been stated (an elevated oestradiol:testosterone ratio is connected with the insulin resistance). Additionally a negative relationship between testosterone and android obesity has been observed. Although nowadays there are more and more facts proving the benefits of the retaining the proper testosterone levels in aging men, the final influence of the testosterone supplementary therapy on atherogenesis is not solved.

  18. Encapsulation of testosterone by chitosan nanoparticles.

    PubMed

    Chanphai, P; Tajmir-Riahi, H A

    2017-05-01

    The loading of testosterone by chitosan nanoparticles was investigated, using multiple spectroscopic methods, thermodynamic analysis, TEM images and modeling. Thermodynamic parameters showed testosterone-chitosan bindings occur mainly via H-bonding and van der Waals contacts. As polymer size increased more stable steroid-chitosan conjugates formed and hydrophobic contact was also observed. The loading efficacy of testosterone-nanocarrier was 40-55% and increased as chitosan size increased. Testosterone encapsulation markedly alters chitosan morphology. Chitosan nanoparticles are capable of transporting testosterone in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Testosterone replacement therapy for older men

    PubMed Central

    Borst, Stephen E; Mulligan, Thomas

    2007-01-01

    Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and with poor cognitive performance. Testosterone replacement in older men has produced benefits, but not consistently so. The inconsistency may arise from differences in the dose and duration of testosterone treatment, as well as selection of the target population. Generally, studies reporting anabolic responses to testosterone have employed higher doses of testosterone for longer treatment periods and have targeted older men whose baseline circulating bioavailable testosterone levels were low. Most studies of testosterone replacement have reported anabolic that are modest compared to what can be achieved with resistance exercise training. However, several strategies currently under evaluation have the potential to produce greater anabolic effects and to do so in a safe manner. At this time, testosterone therapy can not be recommended for the general population of older men. Older men who are hypogonadal are at greater risk for the catabolic effects associated with a number of acute and chronic medical conditions. Future research is likely to reveal benefits of testosterone therapy for some of these special populations. Testosterone therapy produces a number of adverse effects, including worsening of sleep apnea, gynecomastia, polycythemia and elevation of PSA. Efficacy and adverse effects should be assessed frequently throughout the course of therapy. PMID:18225456

  20. Testosterone administration in women with anorexia nervosa.

    PubMed

    Miller, K K; Grieco, K A; Klibanski, A

    2005-03-01

    Anorexia nervosa (AN) is complicated by severe bone loss, cognitive function deficits, and a high prevalence of major depression. We hypothesized that bone formation would increase and depressive symptoms and spatial cognition would improve with short-term physiological testosterone administration. We randomized 33 women with AN and relative testosterone deficiency to transdermal testosterone (Intrinsa, Procter and Gamble Pharmaceuticals, Cincinnati, OH), 150 mug, 300 mug, or placebo, for 3 wk. At baseline, free testosterone correlated with L4 bone density (r = 0.51, P < 0.001), body mass index (r = 0.39, P = 0.02), depressive symptoms (r = -0.44, P = 0.02), and spatial cognition (r = 0.45, P = 0.04). C-terminal propeptide of type 1 collagen levels were higher during testosterone administration than placebo (P = 0.03). The change in propeptide of type 1 collagen correlated with change in free testosterone over 3 wk (r = 0.50, P = 0.02). Osteocalcin and bone-specific alkaline phosphatase did not change. Depressed patients receiving testosterone improved from severely depressed to moderately depressed; the placebo group was unchanged (P = 0.02). Spatial cognition improved in the testosterone group, compared with placebo (P = 0.0015). Therefore, short-term low-dose testosterone may improve depressive symptoms and spatial cognition in women with AN. Low-dose testosterone may also prevent decreased bone formation in AN, but because testosterone did not affect all markers of bone formation studied, further data are needed.

  1. Is testosterone replacement therapy in males with hypogonadism cost-effective? An analysis in Sweden.

    PubMed

    Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira

    2014-01-01

    Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering

  2. Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone: an observational study.

    PubMed

    Haider, Ahmad; Saad, Farid; Doros, Gheorghe; Gooren, Louis

    2014-01-01

    Treatment of obesity with diet and exercise may have short-term success but longer-term maintenance of weight loss is less successful. Obesity is associated with a reduction of serum testosterone, and, vice versa, a reduction in serum testosterone is associated with obesity and features of the metabolic syndrome. To investigate whether restoring serum testosterone to normal in hypo-gonadal obese men is beneficial with regard to weight loss and improvement of the metabolic syndrome. A prospective registry accumulated to 181 men over five years (mean serum testosterone 10.06±1.3 nmol/L (N>12.1), body mass index (BMI) ≥30 kg/m2. Of these men, 72 had diabetes mellitus type 2. All received parenteral testosterone undecanoate 1000 mg/12 weeks for up to five years. Waist circumference (cm) decreased from 111.2±7.54 to 100.46±7.1, weight (kg) from 114.71±11.59 to 93.2±8.49, BMI (kg/m2) from 36.72±3.72 to 30.2±2.59 (all variables statistically significant vs. baseline (p<0.0001) and each year compared to the previous year (p<0.0001)). In the 72 diabetic men, waist circumference (cm) decreased from 112.93±7.16 to 101.48±7.24, weight (kg) from 116.94±11.62 to 94.42±9.42, BMI (kg/m2) from 37.71±3.5 to 30.95±2.69 (all variables statistically significant vs. baseline (p<0.0001) and each year compared to the previous year (p<0.0001)). In all men serum glucose, HbA1c, lipid profiles and blood pressure improved significantly. Testosterone treatment as assessed by hemoglobin, hematocrit, serum prostate specific antigen (PSA) and occurrence of prostate cancer was acceptably safe. Normalizing serum testosterone in obese hypogonadal men, also in those with diabetes type 2, improved their metabolic state. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. All rights reserved.

  3. A multi-institutional observational study of testosterone levels after testosterone pellet (Testopel(®)) insertion.

    PubMed

    McCullough, Andrew R; Khera, Mohit; Goldstein, Irwin; Hellstrom, Wayne J G; Morgentaler, Abraham; Levine, Laurence A

    2012-02-01

    Implantable testosterone pellets were approved by the Food and Drug Administration in 1972 for the treatment of testosterone deficiency syndrome (TDS). Clinical use of this testosterone delivery modality has been limited until its recent reintroduction (Testopel(®) , Slate Pharmaceuticals, Durham, NC, USA). Six academic institutions collaborated and combined their databases to more fully characterize serum testosterone levels after the pellet implantations. To assess the time-dependent serum testosterone levels after subcutaneous testosterone pellets in clinical practice for the treatment of TDS. Data were retrospectively pooled and analyzed from data in six academic institutions. Variables included patient age, total testosterone concentrations before and after implantation, the number of testosterone pellets implanted, and the time from implantation to measurement of serum testosterone concentrations. Three hundred eighty men undergoing 702 insertions were included for analysis using JMP (version 4.0.4; SAS Institute, Cary, NC, USA). Main outcome measures were postimplantation total testosterone levels and investigator-reported adverse events. Testosterone levels as a function of the number of pellets implanted and time from implantation were assessed. Implantation of six to ≥10 testosterone pellets (450 to ≥750 mg) increased total testosterone into the therapeutic range at 1 month postimplantation and sustained therapeutic levels (>300) for 4-6 months. Higher pellet numbers (10-12 pellets) were associated with higher, more consistent, and longer maintenance of testosterone levels within the therapeutic range. Four extrusions and three hematomas were reported early in our experience; other investigator-reported adverse events were generally mild to moderate in nature and transient in duration. No subjects required analgesics. Testosterone pellets (Testopel(®) , Slate Pharmaceuticals) provide sustained levels of testosterone for at least 4 months and up to 6

  4. Testosterone perturbs epidermal permeability barrier homeostasis.

    PubMed

    Kao, J S; Garg, A; Mao-Qiang, M; Crumrine, D; Ghadially, R; Feingold, K R; Elias, P M

    2001-03-01

    Although there are no known gender-related differences in permeability barrier function in adults, estrogens accelerate whereas testosterone retards barrier development in fetal skin, and male fetuses demonstrate slower barrier development than female littermates. Moreover, prenatal administration of the androgen receptor antagonist, flutamide, equalizes developmental rates in male and female fetuses. Therefore, we evaluated the effects of changes in testosterone on barrier homeostasis in adult murine and human skin. Hypogonadal mice (whether by castration or by treatment with systemic flutamide) displayed significantly faster barrier recovery at 3, 6, and 12 h than did controls, and testosterone replacement slowed barrier recovery in castrated mice. Moreover, testosterone directly effects the skin, as topical flutamide also accelerated barrier recovery in normal male mice. These findings appear to be of physiologic significance, since prepubertal male mice (age 5 wk) displayed accelerated barrier recovery in comparison with adult postpubertal (11 wk) males. These studies also appear to be relevant for humans, as a hypopituitary human subject demonstrated repeated changes in barrier recovery in parallel with peaks and nadirs in serum testosterone levels during intermittent testosterone replacement. Mechanistic studies showed that differences in epidermal lipid synthesis do not account for the testosterone-induced functional alterations. Instead, epidermal lamellar body (LB) formation and secretion both decrease, resulting in decreased extracellular lamellar bilayers in testosterone-replete animals. These studies demonstrate that fluctuations in testosterone modulate barrier function, and that testosterone repletion can have negative consequences for permeability barrier homeostasis.

  5. Testosterone: use, misuse and abuse.

    PubMed

    Handelsman, David J

    2006-10-16

    Testosterone is among the oldest drugs in medicine. It has a long efficacy and safety record for its prime role of androgen replacement therapy in men with androgen deficiency. Testosterone and synthetic analogue androgens have also been used in pharmacological androgen therapy (PAT) to produce androgenic effects on marrow, muscle or bone. Although PAT is increasingly being superseded by newer, more expensive drugs, androgens remain cost-effective in many older applications. Androgen misuse is the systematic over-prescribing for unproven medical indications. Misuse is increasingly evident for male ageing ("andropause") and some other clinical conditions. Further trials for new indications for androgens require reliable safety data, but rising costs may make it increasingly attractive to circumvent the need for evidence by promoting off-label mass marketing. Androgen abuse is the illicit self-administration of often massive doses of androgens for non-medical purposes - notably power sports and body building. In parallel with effective detection reducing androgen abuse in elite sports, more focus is needed on non-sporting cosmetic, recreational and occupational androgen abuse. Despite ongoing androgen misuse and abuse, testosterone remains under-prescribed for younger men with classical androgen deficiency that frequently remains undiagnosed.

  6. Testosterone therapy and prostate cancer

    PubMed Central

    Pastuszak, Alexander W.; Rodriguez, Katherine M.; Nguyen, Taylor M.

    2016-01-01

    The use of exogenous testosterone to treat hypogonadism in the men with a history of prostate cancer (CaP) remains controversial due to fears of cancer recurrence or progression. Due to the detrimental impact of hypogonadism on patient quality of life, recent work has examined the safety of testosterone therapy (TTh) in men with a history of CaP. In this review, we evaluate the literature with regards to the safety of TTh in men with a history of CaP. TTh results in improvements in quality of life with little evidence of biochemical recurrence or progression in men with a history of CaP, or de novo cancer in unaffected men. An insufficient amount of evidence is currently available to truly demonstrate the safe use of TTh in men with low risk CaP. In men with high-risk cancer, more limited data suggest that TTh may be safe, but these findings remain inconclusive. Despite the historic avoidance of TTh in men with a history of CaP, the existing body of evidence largely supports the safe and effective use of testosterone in these men, although additional study is needed before unequivocal safety can be demonstrated. PMID:28078223

  7. Fulfilling Desire: Evidence for negative feedback between men’s testosterone, sociosexual psychology, and sexual partner number

    PubMed Central

    Puts, David A.; Pope, Lauramarie E.; Hill, Alexander K.; Cárdenas, Rodrigo A.; Welling, Lisa L. M.; Wheatley, John R.; Breedlove, S. Marc

    2015-01-01

    Across human societies and many nonhuman animals, males have greater interest in uncommitted sex (more unrestricted sociosexuality) than do females. Testosterone shows positive associations with male-typical sociosexual behavior in nonhuman animals. Yet, it remains unclear whether the human sex difference in sociosexual psychology (attitudes and desires) is mediated by testosterone, whether any relationships between testosterone and sociosexuality differ between men and women, and what the nature of these possible relationships might be. In studies to resolve these questions, we examined relationships between salivary testosterone concentrations and sociosexual psychology and behavior in men and women. We measured testosterone in all men in our sample, but only in those women taking oral contraception (OC-using women) in order to reduce the influence of ovulatory cycle variation in ovarian hormone production. We found that OC-using women did not differ from normally-ovulating women in sociosexual psychology or behavior, but that circulating testosterone mediated the sex difference in human sociosexuality and predicted sociosexual psychology in men but not OC-using women. Moreover, when sociosexual psychology was controlled, men’s sociosexual behavior (number of sexual partners) was negatively related to testosterone, suggesting that testosterone drives sociosexual psychology in men and is inhibited when those desires are fulfilled. This more complex relationship between androgen and male sexuality may reconcile some conflicting prior reports. PMID:25644313

  8. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  9. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  10. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  11. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  12. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  13. Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective.

    PubMed

    Mosli, Hala H; Esmat, Ahmed; Atawia, Reem T; Shoieb, Sherif M; Mosli, Hisham A; Abdel-Naim, Ashraf B

    2015-10-23

    Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight &prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone-induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.

  14. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    PubMed Central

    Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

    2016-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

  15. Testosterone Regulates Bone Response to Inflammation

    PubMed Central

    Steffens, J. P.; Herrera, B. S.; Coimbra, L. S.; Stephens, D. N.; Rossa, C.; Spolidorio, L. C.; Kantarci, A.; Van Dyke, T. E.

    2015-01-01

    This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48 h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1β expression was increased in the L group (p < 0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function. PMID:24526374

  16. Suppression of human spermatogenesis by testosterone implants.

    PubMed

    Handelsman, D J; Conway, A J; Boylan, L M

    1992-11-01

    Hormonally induced azoospermia is an effective, reversible form of male contraception; however, some men treated with weekly im testosterone enanthate (TE) injections fail to become azoospermic. As weekly injections cause widely fluctuating and supraphysiological testosterone levels, we tested the hypothesis that more stable, physiological testosterone levels would consistently produce azoospermia. Using a depot testosterone formulation which provides stable, physiological range testosterone levels for up to 6 months, we studied nine men before and after insertion of six 200 mg testosterone implants under the abdominal wall skin and compared the results with 38 men treated in a previous study with weekly im injections of 200 mg TE. Testosterone implants suppressed sperm output to near-azoospermia between the second to fourth postimplant months returning to normal by the sixth postimplant month. The fall in sperm output at the first month was greater after testosterone implants than TE injections (58% vs. 17%, P = 0.011) but similar proportions of men became azoospermic (5/9 vs. 25/38) or severely oligozoospermic (< 1 million/ml; 9/9 vs. 37/38). Plasma testosterone and estradiol levels remained mostly within the eugonadal range after implants but were markedly supraphysiological during TE injections. Both treatments suppressed immunoreactive LH and FSH to undetectable levels by ultrasensitive fluoroimmunoassay. Sex hormone-binding globulin levels were decreased and PRL levels increased by TE injections but neither was changed by testosterone implants. Prostate-specific antigen demonstrated a small rise of marginal significance (P = 0.065) after testosterone implants. Fewer men experienced acne after implants (0/9 vs. 25/38, p = 0.0004). Therefore a depot testosterone preparation with quasi-zero-order release demonstrates higher dose efficiency with similar (but not uniform) efficacy at inducing azoospermia but may cause fewer androgenic side-effects than weekly TE

  17. Delivering enhanced testosterone replacement therapy through nanochannels.

    PubMed

    Ferrati, Silvia; Nicolov, Eugenia; Bansal, Shyam; Zabre, Erika; Geninatti, Thomas; Ziemys, Arturas; Hudson, Lee; Ferrari, Mauro; Goodall, Randal; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

    2015-02-18

    Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Testosterone suppresses oxidative stress in human neutrophils.

    PubMed

    Marin, Douglas Popp; Bolin, Anaysa Paola; dos Santos, Rita de Cassia Macedo; Curi, Rui; Otton, Rosemari

    2010-07-01

    The in vitro effect of testosterone on human neutrophil function was investigated. Blood neutrophils from healthy male subjects were isolated and treated with 10 nM, 0.1 and 10 microM testosterone for 24 h. As compared with untreated cells, the testosterone treatment produced a significant decrease of superoxide production as indicated by the measurement of extra- and intracellular superoxide content. An increment in the production of nitric oxide was observed at 0.1 and 10 microM testosterone concentrations, whereas no effect was found for 10 nM. Intracellular calcium mobilization was significantly increased at 10 nM, whereas it was reduced at 10 microM testosterone. There was an increase in phagocytic capacity at 10 nM and a decrease of microbicidal activity in neutrophils treated with testosterone at 10 microM. Glutathione reductase activity was increased by testosterone treatment, whereas no effect was observed in other antioxidant enzyme activities. An increase in the content of thiol groups was observed at all testosterone concentrations. Lipid peroxidation in neutrophils evaluated by levels of TBARS was decreased at 10 nM and 0.1 microM testosterone. These results indicate the antioxidant properties of testosterone in neutrophils as suggested by reduction of superoxide anion production, and lipid peroxidation, and by the increase in nitric oxide production, glutathione reductase activity and the content of thiol groups. Therefore, the plasma levels of testosterone are important regulators of neutrophil function and so of the inflammatory response.

  19. Testosterone Plasma Concentration is Associated with Insulin Resistance in Male Hypertensive Patients.

    PubMed

    Schianca, Gian Piero Carnevale; Fra, Gian Paolo; Brustia, Fabio; Bellan, Mattia; Pirovano, Alice; Gualerzi, Alessandro; Gentile, Michela; Gibbin, Antonello; Menegatti, Mirta; Bartoli, Ettore; Pirisi, Mario

    2017-03-01

    Background: Low testosterone levels are a common finding among men with Type 2 Diabetes Mellitus (T2DM) and are inversely related to insulin resistance. Whether this relationship holds true in patients with hypertension, but normal glucose tolerance or prediabetes, is unclear. Methods: We recruited 87 male outpatients with essential arterial hypertension, aged 35-70 years. Anthropometric data were collected, an Oral Glucose Tolerance Test (OGTT) performed, and the homeostasis model assessment of insulin resistance (HOMA-IR) score calculated. Follicle-Stimulating Hormone, Luteinizing Hormone, testosterone, Sex Hormone-Binding-Globulin and free-testosterone were measured. The concentrations of sex hormones were compared between normoglucotolerant, prediabetic and diabetic patients. Non-parametric tests were applied as appropriate to verify differences among groups, while multiple linear regression was used to predict the variability of testosterone and free-testosterone. Results: Total serum testosterone concentration was significantly lower in T2DM in comparison to normoglucotolerant subjects (p<0.01) and was inversely related to body mass index (r=- 0.25, p<0.01), waist circumference (r=- 0.27, p<0.01), pre and post-OGTT plasma glucose (r=- 0.4, p<0.0001 and r=- 0.29, p<0.01, respectively), pre and post-OGTT plasma insulin (r=- 0.42, p<0.0001 and r=- 0.42, p<0.0001) and HOMA-IR (r=- 0.46, p<0.0001). Similar associations were observed for free testosterone; HOMA-IR was related to testosterone and free-testosterone even in patients with normal glucose tolerance (r=- 0.47, p<0.01 and r=- 0.34, p<0.05, respectively). At multivariate analysis HOMA-IR was the only variable associated to testosterone (p<0.001) and free-testosterone (p<0.05) plasma concentration. Conclusions: In males with hypertension, the link between insulin sensitivity and hypothalamic-pituitary-gonadal axis is maintained along the entire spectrum of glucose tolerance.

  20. Relationship Between Testosterone and Erectile Dysfunction

    PubMed Central

    Rajfer, Jacob

    2000-01-01

    Although erectile function is clearly androgen dependent, is it just as clear at what level of testosterone erectile dysfunction (ED) begins? Does the decline in testosterone that occurs with aging always produce ED? Are exogenous androgens the answer to ED? The answers range from clear to complex. PMID:16985751

  1. Andropause. Testosterone replacement therapy for aging men.

    PubMed Central

    Bain, J.

    2001-01-01

    OBJECTIVE: To review the rationale for treating symptomatic aging men whose testosterone levels are mildly reduced or low-normal with testosterone replacement therapy. QUALITY OF EVIDENCE: Large-scale multicentre prospective studies on the value of treating andropausal men with hormone therapy do not exist because the whole area of hormone therapy is barely 10 years old. Evidence presented is based on physiologic studies, particularly studies in which treatment has been assessed. These were largely uncontrolled open studies. Studies to date report positive responses to testosterone treatment with very few serious side effects. MAIN MESSAGE: Physicians should consider hypoandrogenism if male patients complain of loss of libido, erectile dysfunction, weakness, fatigue, lethargy, loss of motivation, or mood swings. Less obvious associations with reduced levels of testosterone are anemia and osteoporosis. The main cause of reduced testosterone production is primary gonadal insufficiency, but secondary causes, such as hypothalamic-pituitary disease, should be considered. Evidence shows that most men treated with testosterone will feel better about themselves and their lives. CONCLUSION: Andropause is a term of convenience describing a complex of symptoms in aging men who have low testosterone levels. Physicians should be aware of its existence, should consider ordering tests for men who have symptoms, and should treat carefully selected patients whose serum testosterone levels are low. PMID:11212438

  2. Testosterone deficiency: myth, facts, and controversy.

    PubMed

    Miner, Martin; Barkin, Jack; Rosenberg, Matt T

    2014-06-01

    Testosterone deficiency (TD) afflicts approximately 30% of men ages 40-79 years, with an increase in prevalence strongly associated with aging and common medical conditions including obesity, diabetes, and hypertension. There appears to be a strong relationship between TD and metabolic syndrome, though the relationship is not certain to be causal. Several studies have suggested that repletion of testosterone in deficient men with these comorbidities may indeed reverse or delay their progression. While testosterone repletion has been largely thought of in a sexual realm, we discuss its potential role in general men's health concerns: metabolic, body composition, and its association with decreased all-cause mortality. Recent guidelines and studies have suggested variable prevalence statistics and expanded uses of testosterone repletion in certain populations with both biochemical and clinical signs of testosterone deficiency. Yet, this is not done without risk. A recent randomized placebo-controlled trial of testosterone repletion in elderly frail men with limited mobility has suggested potential negative cardiovascular risks in this older, sicker group of men. Two more recent retrospective studies of variable clinical design and interpretation suggest testosterone poses an increased cardiovascular risk in older men than 65 years and younger men with heart disease. This review examines these and other studies, with practical recommendations for the diagnosis of testosterone deficiency and repletion in middle aged and older men, including an analysis of treatment modalities and areas of concern and uncertainty.

  3. Testosterone, Marital Quality, and Role Overload

    ERIC Educational Resources Information Center

    Booth, Alan; Johnson, David R.; Granger, Douglas A.

    2005-01-01

    In a sample of established working- and middle-class families with school-aged children (N= 307 wives and 307 husbands), neither husbands nor wives testosterone showed a direct connection with marital quality. In contrast, the association between husbands' testosterone and positive and negative marital quality (as evaluated by both spouses) was…

  4. [Testosterone--effects, metabolism and genetic determination].

    PubMed

    Schmidtová, E

    2008-01-01

    Testosterone (C19H28O2), the main testicular hormone, is 19-carbonic steroid substance with -OH group in position 17. Precursor for its synthesis is cholesterol, or possibly androstendione released by adrenal cortex. Testosterone is produced in smooth endoplasmatic reticulum of Leydig cells of testes. Apart from testes it is also produced in adrenal cortex, liver, kidneys, in fat and muscle tissue, even though in smaller extent--around 5% (Bidlingmaier, F. et al., 1986). Approximately 4-9 mg (13.9-31.2 nmol/l) of testosterone is daily produced in healthy men. Absolute majority, around 99% from overall plasmatic testosterone is bound to albumin, erythrocytes, but mainly to sex hormone binding globulin (SHBG) (Diver, M.J. et al., 2003). Only small proportion (1-2%) of testosterone circulates as free fraction (Ostatníková, D., 2003). Production and secretion of the main androgen in testes is regulated by well known and accepted axis of hypothalamus, hypophysis and testes. Testosterone and its metabolite dihydrotestosterone can influence the expression of genes, development of masculine type of habitus and behavior, acting via androgen receptor (AR) (Zitzmann, M. and Nieschlag, E., 2003). Testosterone can affect also via its metabolites, whose production is conditioned by enzymes. In peripheral tissues is testosterone converted via aromatase to estradiol and via 5alpha-reductase to dihydrotestosterone (Weber, K.S. et al., 1999).

  5. Testosterone, Marital Quality, and Role Overload

    ERIC Educational Resources Information Center

    Booth, Alan; Johnson, David R.; Granger, Douglas A.

    2005-01-01

    In a sample of established working- and middle-class families with school-aged children (N= 307 wives and 307 husbands), neither husbands nor wives testosterone showed a direct connection with marital quality. In contrast, the association between husbands' testosterone and positive and negative marital quality (as evaluated by both spouses) was…

  6. Effects of varicocelectomy on serum testosterone

    PubMed Central

    Whelan, Patrick

    2016-01-01

    Varicocele is most often surgically repaired due to male infertility, however, has recently been linked to low serum testosterone. This paper serves to review the current literature regarding varicocele and its subsequent repair on serum testosterone. Twenty-eight human studies were identified with fifteen showing improved serum testosterone after repair. The majority of the studies that demonstrated improvement had preoperative testosterone levels that were low or below normal. Additionally, multiple well-designed studies with control groups not undergoing surgical repair demonstrated significant difference between groups. This improvement was less observed in studies with normal preoperative serum testosterone. A majority of these patients studied were presenting for infertility. It remains to be determined if these findings can be reproduced in men without infertility. The findings suggest that microsurgical varicocele repair can improve serum testosterone in men with low levels preoperatively in appropriately counseled men. It remains to be seen whether varicocele repair can help prevent the development of low testosterone in the future or which patients are at risk of developing low testosterone due to varicocele. PMID:28078218

  7. The appropriateness and persistence of testosterone replacement therapy in Ontario.

    PubMed

    Martins, Diana; Yao, Zhan; Tadrous, Mina; Shah, Baiju R; Juurlink, David N; Mamdani, Muhammad M; Gomes, Tara

    2017-02-01

    To examine the concordance between testosterone replacement therapy (TRT) use and established reimbursement criteria, as well as compare the persistence of use among available formulations (injectable, oral, topical gel, transdermal patch) among elderly men in Ontario, Canada. We conducted a retrospective cohort study of men aged 66 years or older in Ontario newly treated with testosterone between 1 January 2009 and 31 December 2012 using linked health administrative data. Continuous use was defined on the basis of prescription refills issued within 180 days of the preceding prescription. We studied men who received at least two consecutive TRT prescriptions. We estimated the prevalence of hypogonadism, human immunodeficiency virus, specialist visits and lab tests for serum testosterone prior to initiation of TRT to investigate concordance with prescribing criteria. We also performed a Kaplan-Meier analysis to test for differences in the median time to discontinuation among formulations. Among the 4797 men who received at least two TRT prescriptions, only 38.7% met the reimbursement criteria for use prior to initiating therapy. The median time to discontinuation differed significantly among formulations and was longest among recipients of oral TRT products (383 days), and lower for recipients of topical gels (319 days), injectable (283 days) and transdermal patches (160 days; Log-rank test p < 0.001). A large proportion of older men in Ontario do not appear to meet reimbursement criteria prior to commencing therapy, and many discontinue TRT within a year of initiation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

    PubMed

    Regis, Lucas; Planas, Jacques; Carles, Joan; Maldonado, Xavier; Comas, Inma; Ferrer, Roser; Morote, Juan

    2017-01-01

    The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. [Testosterone deficiency, metabolic syndrome and diabetes mellitus].

    PubMed

    Fernández-Miró, Mercè; Chillarón, Juan J; Pedro-Botet, Juan

    2016-01-15

    Testosterone deficiency in adult age is associated with a decrease in libido, energy, hematocrit, muscle mass and bone mineral density, as well as with depression. More recently, testosterone deficiency has also been associated with various components of the metabolic syndrome, which in turn is associated with a five-fold increase in the risk of cardiovascular disease. Low testosterone levels are associated with increased insulin resistance, increase in fat mass, low HDL cholesterol, higher triglyceride levels and hypertension. Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and/or metabolic syndrome has shown reductions in insulin resistance, total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters.

  10. Testosterone Replacement Therapy and the Cardiovascular System.

    PubMed

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  11. Testosterone induces off-line perceptual learning.

    PubMed

    Wright, Nicholas D; Edwards, Thomas; Fleming, Stephen M; Dolan, Raymond J

    2012-12-01

    Perceptual learning operates on distinct timescales. How different neuromodulatory systems impact on learning across these different timescales is poorly understood. Here, we test the causal impact of a novel influence on perceptual learning, the androgen hormone testosterone, across distinct timescales. In a double-blind, placebo- controlled, cross-over study with testosterone, subjects undertook a simple contrast detection task during training sessions on two separate days. On placebo, there was no learning either within training sessions or between days, except for a fast, rapidly saturating, improvement early on each testing day. However, testosterone caused "off-line" learning, with no learning seen within training sessions, but a marked performance improvement over the days between sessions. This testosterone-induced learning occurred in the absence of changes in subjective confidence or introspective accuracy. Our findings show that testosterone influences perceptual learning on a timescale consistent with an influence on "off-line" consolidation processes.

  12. Testosterone

    MedlinePlus

    ... ovary syndrome Precocious puberty Prolactinoma Testicular cancer Testicular failure Review Date 2/3/2016 Updated by: Brent Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, Seattle, WA. Also reviewed by David ...

  13. Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men

    PubMed Central

    Olubodun, Joel O; Ochs, Hermann R; von Moltke, Lisa L; Roubenoff, Ronenn; Hesse, Leah M; Harmatz, Jerold S; Shader, Richard I; Greenblatt, David J

    2003-01-01

    Aims The influence of ageing on the pharmacokinetics of zolpidem, an extensively prescribed hypnotic medication, was evaluated in healthy human volunteers. Methods A series of 16 elderly (age: 61–85 years) and 24 young (age: 22–42 years) volunteers received single 5 mg oral doses of zolpidem tartrate. Serum zolpidem concentrations were determined by HPLC with fluorescence detection in samples drawn during 8 h after dosage. The effect of testosterone on zolpidem biotransformation was evaluated in vitro using human liver microsomes. Possible induction of CYP3A protein expression and function was studied in cultured human hepatocytes. Results Among men, apparent oral clearance of zolpidem was decreased in elderly compared to young subjects (3.8 vs 11.0 ml min−1 kg−1, P < 0.01), Cmax was increased (93 vs 40 ng ml−1, P < 0.01), and half-life increased (2.7 vs 1.5 h, P < 0.03). Among women, zolpidem oral clearance was decreased in the elderly (3.0 vs 5.8 ml min−1 kg−1, P < 0.02), Cmax increased (108 vs 60 ng ml−1, P < 0.001), with no difference in t1/2 (2.3 vs 2.4 h). Among male subjects, free serum testosterone concentrations were lower in the elderly (10.5 vs 19.0 pg ml−1, P < 0.01), and were significantly correlated with zolpidem clearance (r2 = 0.46, P < 0.001). Multiple regression analysis indicated a greater relative contribution of serum testosterone than age to the oral clearance of zolpidem among men. In human liver microsomes, co-incubation of zolpidem (10 µm) with varying concentrations of testosterone produced activation of biotransformation of zolpidem to its principal hydroxylated metabolite. Maximum activation was achieved at equimolar concentrations of testosterone (10 µm). However, testosterone did not induce immunoactive CYP3A4 expression or catalytic function in cultured human hepatocytes. Conclusions The increased Cmax and lower oral clearance of zolpidem in the elderly are consistent with recommendations of lower clinical doses of

  14. Testosterone ethosomes for enhanced transdermal delivery.

    PubMed

    Ainbinder, Denize; Touitou, Elka

    2005-01-01

    Physiological decrease in testosterone levels in men with age causes various changes with clinical significance. Recent testosterone replacement therapy is based mainly on transdermal nonpatch delivery systems. These products have the drawback of application on extremely large areas to achieve required hormone blood levels. The objective of the present study was to design and test a testosterone nonpatch formulation using ethosomes for enhanced transdermal absorption. The ethosomal formulation was characterized by transmission electron microscopy and dynamic light scattering for structure and size distribution and by ultracentrifugation for entrapment capacity. To evaluate the feasibility of this delivery system to enhance testosterone permeation through the skin, first the systemic absorption in rats was compared with a currently used gel (AndroGel). Further, theoretical estimation of testosterone blood concentration following ethosomal application in men was made. For this purpose, in vitro permeation experiments through human skin were performed to establish testosterone skin permeation values. In the design of these experiments, testosterone solubility in various solutions was measured and the effect of the receiver medium on the skin barrier function was assessed by confocal laser scanning microscopy. Theoretical estimation shows that testosterone human plasma concentration value in the upper part of the physiological range could be achieved by application of the ethosomal formulation on an area of 40 cm(2). This area is about 10 times smaller than required with current nonpatch formulations. Our work shows that the ethosomal formulation could enhance testosterone systemic absorption and also be used for designing new products that could solve the weaknesses of the current testosterone replacement therapies.

  15. Effect of zinc and selenium supplementation on serum testosterone and plasma lactate in cyclist after an exhaustive exercise bout.

    PubMed

    Shafiei Neek, Leila; Gaeini, Abas Ali; Choobineh, Siroos

    2011-12-01

    Zinc and selenium are essential minerals and have roles for more than 300 metabolic reactions in the body. The purpose of this study was to investigate how exhaustive exercise affects testosterone levels and plasma lactate in cyclists who were supplemented with oral zinc and selenium for 4 weeks. For this reason, 32 male road cyclists were selected equally to four groups: PL group, placebo; Zn group, zinc supplement (30 mg/day); Se group, selenium supplement (200 μg/day); and Zn-Se group, zinc-selenium supplement. After treatment, free, total testosterone, and lactate levels of subjects were determined before and after exhaustive exercise. Resting total, free testosterone, and lactate levels did not differ significantly between groups, and were increased by exercise (P > 0.05). Serum total testosterone levels in Zn group were higher than in Se group after exercise (P < 0.05). Serum-free testosterone levels in the Zn group were higher than the other groups (P < 0.05).There was an insignificant difference between levels of lactate in the four groups after exercise (P > 0.05). The results showed that 4-week simultaneous and separately zinc and selenium supplementation had no significant effect on resting testosterone and lactate levels of subjects who consume a zinc and selenium sufficient diet. It might be possible that the effect of zinc supplementation on free testosterone depends on exercise.

  16. SB223412, a neurokinin-3 receptor-selective antagonist, suppresses testosterone secretion in male guinea pigs.

    PubMed

    Nakamura, Sho; Ito, Yoshiko; Yamamoto, Koki; Takahashi, Chudai; Dai, Mingdao; Tanahashi, Miyu; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Oishi, Shinya; Maeda, Kei-Ichiro; Matsuda, Fuko

    2017-10-15

    Guinea pigs are important zoo animals and have been recommended for animal-assisted activities or therapy, however there are problems concerning testosterone inducing aggressive or sexual behaviors in male guinea pigs. Testicular testosterone secretion is regulated by pulsatile gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) release in mammals. The mechanism generating GnRH/LH pulses is thought to be governed by kisspeptin neurons, which coexpress neurokinin B (NKB) and dynorphin A (Dyn), in the arcuate nucleus (ARC). Kisspeptin neurons in the ARC are frequently referred to as KNDy neurons. The purpose of this study was to examine whether the antagonization of NKB-neurokinin-3 receptor (NK3R) signaling can manipulate testosterone secretion in male guinea pigs. A single subcutaneous administration or 7 days of oral administration of an NK3R-selective antagonist, SB223412 (50 mg/body), significantly decreased plasma testosterone levels in male guinea pigs. In vitro binding assays confirmed that SB223412 has a high affinity to guinea pig NK3R. These results suggest that SB223412 could be used as an orally-available compound to suppress testosterone levels in male guinea pigs. Double labeling in situ hybridization of kisspeptin and either NKB or Dyn showed that kisspeptin-expressing neurons contained NKB (77.9%) or Dyn (62.3%) in the ARC, suggesting the presence of KNDy neurons in the ARC of guinea pigs. In conclusion, the present study shows that SB223412 could be a candidate compound to suppress testosterone secretion in male guinea pigs for controlling sexual and aggressive behaviors in the species. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial.

    PubMed

    Ng Tang Fui, Mark; Prendergast, Luke A; Dupuis, Philippe; Raval, Manjri; Strauss, Boyd J; Zajac, Jeffrey D; Grossmann, Mathis

    2016-10-07

    Whether testosterone treatment has benefits on body composition over and above caloric restriction in men is unknown. We hypothesised that testosterone treatment augments diet-induced loss of fat mass and prevents loss of muscle mass. We conducted a randomised double-blind, parallel, placebo controlled trial at a tertiary referral centre. A total of 100 obese men (body mass index ≥ 30 kg/m(2)) with a total testosterone level of or below 12 nmol/L and a median age of 53 years (interquartile range 47-60) receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of 10-weekly intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). The main outcome measures were the between-group difference in fat and lean mass by dual-energy X-ray absorptiometry, and visceral fat area (computed tomography). A total of 82 men completed the study. At study end, compared to controls, cases had greater reductions in fat mass, with a mean adjusted between-group difference (MAD) of -2.9 kg (-5.7 to -0.2; P = 0.04), and in visceral fat (MAD -2678 mm(2); -5180 to -176; P = 0.04). Although both groups lost the same lean mass following VLED (cases -3.9 kg (-5.3 to -2.6); controls -4.8 kg (-6.2 to -3.5), P = 0.36), cases regained lean mass (3.3 kg (1.9 to 4.7), P < 0.001) during weight maintenance, in contrast to controls (0.8 kg (-0.7 to 2.3), P = 0.29) so that, at study end, cases had an attenuated reduction in lean mass compared to controls (MAD 3.4 kg (1.3 to 5.5), P = 0.002). While dieting men receiving placebo lost both fat and lean mass, the weight loss with testosterone treatment was almost exclusively due to loss of body fat. clinicaltrials.gov, identifier NCT01616732 , registration date: June 8, 2012.

  18. Testosterone and cardiovascular disease in men

    PubMed Central

    Morris, Paul D; Channer, Kevin S

    2012-01-01

    Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ‘Perspectives' article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ‘cause' versus ‘effect' controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease. PMID:22522504

  19. Testosterone and reproductive effort in male primates.

    PubMed

    Muller, Martin N

    2016-09-08

    Considerable evidence suggests that the steroid hormone testosterone mediates major life-history trade-offs in vertebrates, promoting mating effort at the expense of parenting effort or survival. Observations from a range of wild primates support the "Challenge Hypothesis," which posits that variation in male testosterone is more closely associated with aggressive mating competition than with reproductive physiology. In both seasonally and non-seasonally breeding species, males increase testosterone production primarily when competing for fecund females. In species where males compete to maintain long-term access to females, testosterone increases when males are threatened with losing access to females, rather than during mating periods. And when male status is linked to mating success, and dependent on aggression, high-ranking males normally maintain higher testosterone levels than subordinates, particularly when dominance hierarchies are unstable. Trade-offs between parenting effort and mating effort appear to be weak in most primates, because direct investment in the form of infant transport and provisioning is rare. Instead, infant protection is the primary form of paternal investment in the order. Testosterone does not inhibit this form of investment, which relies on male aggression. Testosterone has a wide range of effects in primates that plausibly function to support male competitive behavior. These include psychological effects related to dominance striving, analgesic effects, and effects on the development and maintenance of the armaments and adornments that males employ in mating competition.

  20. Testosterone, cortisol, and human competition.

    PubMed

    Casto, Kathleen V; Edwards, David A

    2016-06-01

    Testosterone and cortisol figure prominently in the research literature having to do with human competition. In this review, we track the history of this literature, concentrating particularly on major theoretical and empirical contributions, and provide commentary on what we see as important unresolved issues. In men and women, athletic competition is typically associated with an increase in testosterone (T) and cortisol (C). Hormone changes in response to non-athletic competition are less predictable. Person (e.g., power motivation, mood, aggressiveness, social anxiety, sex, and baseline levels of T and C) and context (e.g., whether a competition is won or lost, the closeness of the competition, whether the outcome is perceived as being influenced by ability vs. chance, provocations) factors can influence hormone responses to competition. From early on, studies pointed to a positive relationship between T and dominance motivation/status striving. Recent research, however, suggests that this relationship only holds for individuals with low levels of C - this is the core idea of the dual-hormone hypothesis, and it is certain that the broadest applications of the hypothesis have not yet been realized. Individuals differ with respect to the extent to which they embrace competition, but the hormonal correlates of competitiveness remain largely unexplored. Although rapid increases in both T and C associated with competition are likely adaptive, we still know very little about the psychological benefits of these hormonal changes. Administration studies have and will continue to contribute to this inquiry. We close with a discussion of what, we think, are important methodological and mechanistic issues for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Testosterone and aggressive behavior in man.

    PubMed

    Batrinos, Menelaos L

    2012-01-01

    Atavistic residues of aggressive behavior prevailing in animal life, determined by testosterone, remain attenuated in man and suppressed through familial and social inhibitions. However, it still manifests itself in various intensities and forms from; thoughts, anger, verbal aggressiveness, competition, dominance behavior, to physical violence. Testosterone plays a significant role in the arousal of these behavioral manifestations in the brain centers involved in aggression and on the development of the muscular system that enables their realization. There is evidence that testosterone levels are higher in individuals with aggressive behavior, such as prisoners who have committed violent crimes. Several field studies have also shown that testosterone levels increase during the aggressive phases of sports games. In more sensitive laboratory paradigms, it has been observed that participant's testosterone rises in the winners of; competitions, dominance trials or in confrontations with factitious opponents. Aggressive behavior arises in the brain through interplay between subcortical structures in the amygdala and the hypothalamus in which emotions are born and the prefrontal cognitive centers where emotions are perceived and controlled. The action of testosterone on the brain begins in the embryonic stage. Earlier in development at the DNA level, the number of CAG repeats in the androgen receptor gene seems to play a role in the expression of aggressive behavior. Neuroimaging techniques in adult males have shown that testosterone activates the amygdala enhancing its emotional activity and its resistance to prefrontal restraining control. This effect is opposed by the action of cortisol which facilitates prefrontal area cognitive control on impulsive tendencies aroused in the subcortical structures. The degree of impulsivity is regulated by serotonin inhibiting receptors, and with the intervention of this neurotransmitter the major agents of the neuroendocrine

  2. Effects of Testosterone Treatment in Older Men.

    PubMed

    Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R; Matsumoto, Alvin M; Stephens-Shields, Alisa J; Cauley, Jane A; Gill, Thomas M; Barrett-Connor, Elizabeth; Swerdloff, Ronald S; Wang, Christina; Ensrud, Kristine E; Lewis, Cora E; Farrar, John T; Cella, David; Rosen, Raymond C; Pahor, Marco; Crandall, Jill P; Molitch, Mark E; Cifelli, Denise; Dougar, Darlene; Fluharty, Laura; Resnick, Susan M; Storer, Thomas W; Anton, Stephen; Basaria, Shehzad; Diem, Susan J; Hou, Xiaoling; Mohler, Emile R; Parsons, J Kellogg; Wenger, Nanette K; Zeldow, Bret; Landis, J Richard; Ellenberg, Susan S

    2016-02-18

    Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was

  3. Effects of Testosterone Treatment in Older Men

    PubMed Central

    Snyder, P.J.; Bhasin, S.; Cunningham, G.R.; Matsumoto, A.M.; Stephens-Shields, A.J.; Cauley, J.A.; Gill, T.M.; Barrett-Connor, E.; Swerdloff, R.S.; Wang, C.; Ensrud, K.E.; Lewis, C.E.; Farrar, J.T.; Cella, D.; Rosen, R.C.; Pahor, M.; Crandall, J.P.; Molitch, M.E.; Cifelli, D.; Dougar, D.; Fluharty, L.; Resnick, S.M.; Storer, T.W.; Anton, S.; Basaria, S.; Diem, S.J.; Hou, X.; Mohler, E.R.; Parsons, J.K.; Wenger, N.K.; Zeldow, B.; Landis, J.R.; Ellenberg, S.S.

    2016-01-01

    BACKGROUND Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. METHODS We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials — the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. RESULTS Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy–Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. CONCLUSIONS In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or

  4. The role of testosterone in social interaction.

    PubMed

    Eisenegger, Christoph; Haushofer, Johannes; Fehr, Ernst

    2011-06-01

    Although animal researchers established the role of testosterone as a 'social hormone' decades ago, the investigation of its causal influence on human social behaviors has only recently begun. Here, we review and discuss recent studies showing the causal effects of testosterone on social interactions in animals and humans, and outline the basic neurobiological mechanisms that might underlie these effects. Based on these recent findings, we argue that the role of testosterone in human social behavior might be best understood in terms of the search for, and maintenance of, social status. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Testosterone patches for female sexual dysfunction.

    PubMed

    2009-03-01

    There is some suggestion of a link between sexual dysfunction in postmenopausal women and low circulating concentrations of testosterone.1 This underlies the development of a new transdermal testosterone patch (black triangle down Intrinsa - Procter & Gamble) that has recently been licensed in the UK for the treatment of women who have hypoactive sexual desire disorder (HSDD) following a menopause induced by surgery (i.e. bilateral salpingooophorectomy and hysterectomy) and who are receiving concomitant oestrogen replacement therapy.2 Here we discuss the diagnosis of HSDD, as well as the evidence for using transdermal testosterone patches in women in whom this diagnosis is made.

  6. Testosterone replacement therapy and voiding dysfunction

    PubMed Central

    Baas, Wesley

    2016-01-01

    Testosterone replacement therapy (TRT) represents an increasing popular treatment option for men with late-onset hypogonadism (LOH). Because of unsubstantiated beliefs of testosterone’s effect on the prostate, the FDA has recently placed a warning on testosterone products, stating that TRT may worsen benign prostatic hyperplasia (BPH). Within this review article we have demonstrated the current understanding of the physiology of testosterone and its relationship with prostatic and lower urinary tract physiology. The current evidence suggests that not only does TRT not worsen lower urinary tract symptoms (LUTS), but that hypogonadism itself is an important risk factor for LUTS/BPH. PMID:28078221

  7. Andropause or male menopause? Rationale for testosterone replacement therapy in older men with low testosterone levels.

    PubMed

    Cunningham, Glenn R

    2013-01-01

    To provide rationale for testosterone replacement therapy (TRT) in older men with low testosterone levels and symptoms consistent with testosterone deficiency. The relevant literature was reviewed using PubMed. Cross-sectional and longitudinal population-based studies indicate that total and free testosterone levels fall with aging, and they may be accompanied by symptoms consistent with androgen deficiency. Testosterone treatment of younger men with very low testosterone levels and hypothalamic, pituitary, or testicular disease is associated with improvements in symptoms, body composition, bone density, and hematocrit/hemoglobin. Studies evaluating testosterone treatment of older men with low testosterone levels are limited, but they suggest some increase in fat free mass, some decrease in fat mass, and some increase in bone density of the lumbar spine and femoral neck. The Testosterone Trial should provide definitive information regarding the potential benefits of TRT in men ≥65 years of age. If efficacy is confirmed, we will still need more information regarding the risks of TRT in older men.

  8. Testosterone therapy in men with testosterone deficiency: Are we beyond the point of no return?

    PubMed Central

    2016-01-01

    Although testosterone therapy in men with testosterone deficiency was introduced in the early 1940s, utilization of this effective treatment approach in hypogonadal men is met with considerable skepticism and resistance. Indeed, for decades, the fear that testosterone may cause prostate cancer has hampered clinical progress in this field. Nevertheless, even after considerable knowledge was acquired that this fear is unsubstantiated, many in the medical community remain hesitant to utilize this therapeutic approach to treat men with hypogonadism. As the fears concerning prostate cancer have subsided, a new controversy regarding use of testosterone therapy and increase in cardiovascular disease was introduced. Although the new controversy was based on one ill-fated clinical trial, one meta-analysis with studies that utilized unapproved formulation in men with liver cirrhosis, and two retrospective studies with suspect or nonvalidated statistical methodologies and database contaminations, the flames of such controversy were fanned by the lay press and academics alike. In this review we discuss the adverse effect of testosterone deficiency and highlight the numerous proven benefits of testosterone therapy on men's health and debunk the myth that testosterone therapy increases cardiovascular risk. Ultimately, we believe that there is considerable scientific and clinical evidence to suggest that testosterone therapy is safe and effective with restoration of physiological levels in men with testosterone deficiency, irrespective of its etiology. PMID:27847912

  9. Second to fourth digit ratio, adult testosterone level and testosterone deficiency.

    PubMed

    García-Cruz, Eduardo; Huguet, Jorge; Piqueras, Marta; Ribal, María J; Alcaraz, Antonio

    2012-01-01

    The ratio of the second and fourth finger lengths (2D/4D) is related to intrauterine exposure to testosterone. The relationship between 2D/4D and adult hormonal pattern is controversial. The aim of our study was to determine if there was a relationship between adult serum testosterone levels and the 2D/4D ratio. We prospectively recruited 204 consecutive patients referred for transrectal prostate biopsy between January 2008 and June 2009. The same physician performed clinical examinations, 2D/4D measurements and the transrectal biopsy in all cases. Cut-off points of 231 and 346 ng/dL testosterone (8 and 12 nmol/L) were used. 2D/4D determination was done with a vernier calliper on the left hand. The hormonal profile (testosterone and sexual hormone binding globulin) of the patients was determined between 7.00 am and 11.00 am. Age, weight, height, body mass index, toxic habits, digital rectal examination, prostate-specific antigen and 2D and 4D measurements were recorded prospectively. The mean age was 67 ± 7 years and the mean testosterone level was 413 ± 18 ng/dL (14.33 ± 0.62 nmol/L). The percentages of patients with testosterone <231 ng/dL (8 nmol/L) and testosterone <346 ng/dL (12 nmol/L) were 6.1 and 30.6 respectively. Univariate analysis showed that low 2D/4D ratios were related to higher levels of testosterone (B=-741.98; β=-0.165, P= 0.045) and also with low prevalence of biochemical hypogonadism (testosterone <346 ng/dL). Mean 2D/4D ratio in patients with testosterone >346 ng/dL was lower than in patients with testosterone <346 ng/dL (2D/4D 0.97 ± 0.037 vs 0.99 ± 0.043 depending on their hormonal status, P= 0.05). High 2D/4D ratio was associated with low testosterone serum levels (P= 0.046). The 2D/4D ratio is related to adult testosterone levels and the presence of testosterone deficiency syndrome. Patients with high 2D/4D ratios have lower testosterone levels and higher risk of testosterone deficiency syndrome. © 2011 THE AUTHORS. BJU INTERNATIONAL

  10. Testosterone inhibits trust but promotes reciprocity.

    PubMed

    Boksem, Maarten A S; Mehta, Pranjal H; Van den Bergh, Bram; van Son, Veerle; Trautmann, Stefan T; Roelofs, Karin; Smidts, Ale; Sanfey, Alan G

    2013-11-01

    The steroid hormone testosterone has been associated with behavior intended to obtain or maintain high social status. Although such behavior is typically characterized as aggressive and competitive, it is clear that high social status is achieved and maintained not only through antisocial behavior but also through prosocial behavior. In the present experiment, we investigated the impact of testosterone administration on trust and reciprocity using a double-blind randomized control design. We found that a single dose of 0.5 mg of testosterone decreased trust but increased generosity when repaying trust. These findings suggest that testosterone may mediate different types of status-seeking behavior. It may increase competitive, potentially aggressive, and antisocial behavior when social challenges and threats (i.e., abuse of trust and betrayal) need to be considered; however, it may promote prosocial behavior in the absence of these threats, when high status and good reputation may be best served by prosocial behavior.

  11. Serum Testosterone Levels in Sex Offenders.

    ERIC Educational Resources Information Center

    Gurnani, Prem D.; Dwyer, Margretta

    1986-01-01

    Reports that with the increase in diagnosis of offenders across the nation, physicians and psychiatric personnel need to be aware of low testosterone as a possible indicator of hypo-sexuality and possible concurrent offending behavior. (Author/ABB)

  12. [Testosterone and bone: indications and limitations].

    PubMed

    Stoll, Delphine; Puder, Jardena J; Lamy, Olivier

    2011-06-15

    Osteoporosis incidence increases exponentially with age in men and hypogonadism represents a risk factor. Sex steroids levels are correlated to bone mineral density and to fracture prevalence. Most studies demonstrate an improvement in bone mineral density in men with hypogonadism as a result of testosterone therapy. Nevertheless there are no data evaluating the effect of testosterone therapy on fractures in men. Approximately 20% of men older than 60 have a total testosterone level lower than the lower limit of the reference range but there is no true consensus on the definition of hypogonadism in older men. In older men we recommend to treat only if total morning testosterone levels are < 8 nmol/l or even < 6,9 nmol/l on several occasions in the absence of any reversible illness and if there is no contraindication for treatment.

  13. Serum Testosterone Levels in Sex Offenders.

    ERIC Educational Resources Information Center

    Gurnani, Prem D.; Dwyer, Margretta

    1986-01-01

    Reports that with the increase in diagnosis of offenders across the nation, physicians and psychiatric personnel need to be aware of low testosterone as a possible indicator of hypo-sexuality and possible concurrent offending behavior. (Author/ABB)

  14. Testosterone abolishes implicit subordination in social anxiety.

    PubMed

    Terburg, David; Syal, Supriya; Rosenberger, Lisa A; Heany, Sarah J; Stein, Dan J; Honk, Jack van

    2016-10-01

    Neuro-evolutionary theories describe social anxiety as habitual subordinate tendencies acquired through a recursive cycle of social defeat and submissive reactions. If so, the steroid hormone testosterone might be of therapeutic value, as testosterone is a main force behind implicit dominance drive in many species including humans. We combined these two theories to investigate whether the tendency to submit to the dominance of others is an implicit mechanism in social anxiety (Study-1), and whether this can be relieved through testosterone administration (Study-2). Using interactive eye-tracking we demonstrate that socially anxious humans more rapidly avert gaze from subliminal angry eye contact (Study-1). We replicate this effect of implicit subordination in social anxiety in an independent sample, which is subsequently completely abolished after a single placebo-controlled sublingual testosterone administration (Study-2). These findings provide crucial evidence for hormonal and behavioral treatment strategies that specifically target mechanisms of dominance and subordination in social anxiety.

  15. Diagnosis and management of testosterone deficiency

    PubMed Central

    McBride, James A; Carson, Culley C; Coward, Robert M

    2015-01-01

    Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD. PMID:25532575

  16. Diagnosis and management of testosterone deficiency.

    PubMed

    McBride, James A; Carson, Culley C; Coward, Robert M

    2015-01-01

    Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.

  17. Diagnosing and managing low serum testosterone.

    PubMed

    Rivas, Ana Marcella; Mulkey, Zachary; Lado-Abeal, Joaquin; Yarbrough, Shannon

    2014-10-01

    Measuring testosterone levels became easier in the 1970s, and it wasn't long before levels were being checked in men across all age groups. At that time, several authors reported an age-associated decline of serum testosterone levels beginning in the fourth or fifth decades of life. Other studies found that the decline in testosterone with age might be more related to comorbidities that develop in many aging men. Aggressive marketing campaigns by pharmaceutical companies have led to increased awareness of this topic, and primary care physicians are seeing more patients who are concerned about "low T." Unfortunately, testosterone replacement therapy has not been straightforward. Many men with low testosterone levels have no symptoms, and many men with symptoms who receive treatment and reach goal testosterone levels have no improvement in their symptoms. The actual prevalence of hypogonadism has been estimated to be 39% in men aged 45 years or older presenting to primary care offices in the United States. As the US population ages, this number is likely to increase. This article, targeted to primary care physicians, reviews the concept of late-onset hypogonadism, describes how to determine the patients who might benefit from therapy, and offers recommendations regarding the workup and initiation of treatment.

  18. Effect of low-dose testosterone treatment on androgen regulated proteins prostate specific antigen and sex hormone binding globulin in short prepubertal boys: lack of initiation of puberty.

    PubMed

    Gupta, M K; Brown, D C; Faiman, C; Kelnar, C J H; Wu, F C W

    2003-01-01

    The efficacy of testosterone undecanoate (TU) treatment in constitutional delay of growth (CHD) is well recognized. We investigated its role in initiating puberty. Sera taken prior to, just after 6 months on and after 6 months off treatment with TU (20 mg daily) were analyzed from eight boys and compared to results from eight boys receiving placebo. Prostate specific antigen (PSA) and sex hormone binding globulin (SHBG), sleep-entrained pulsatility and mean overnight luteinizing hormone (mLH), and morning testosterone (T) levels were measured. Free androgen index (FAI) was calculated. Testicular volume (TV) and growth parameters were assessed. During treatment, there was a significant increase in height velocity in boys taking TU vs placebo (mean +/- SD: 5.7 +/- 2.0 vs 3.2 +/- 0.9 cm/year, p = 0.008) but no significant differences were observed in regard to LH pulsatility, mLH, T, SHBG, FAI, PSA and TV values. PSA was detectable in four patients (two each in the TU and placebo groups) at 6 months off treatment indicating pubertal progression. Among the hormones measured, only pretreatment mLH levels were significantly higher in the PSA-positive patients compared to 12 PSA-negative patients (mean +/- SEM: 1.5 +/- 0.39 vs 0.37 +/- 0.06 IU/l, p < 0.001). In conclusion, TU treatment shows no significant effect on initiation or advancement of puberty despite its resultant growth acceleration. Among the hormonal changes studied, mLH levels were the earliest indicator of pubertal initiation.

  19. Inhibition of testosterone-induced hyperplasia of the prostate of sprague-dawley rats by pumpkin seed oil.

    PubMed

    Gossell-Williams, M; Davis, A; O'Connor, N

    2006-01-01

    The oil from the pumpkin (Cucurbita pepo) seed is claimed to be useful in the management of benign prostatic hyperplasia. This investigation seeks to examine the effect of pumpkin seed oil on testosterone-induced hyperplasia of the prostate of rats. Hyperplasia was induced by subcutaneous administration of testosterone (0.3 mg/100 g of body weight) for 20 days. Simultaneous oral administration of either pumpkin seed oil (2.0 and 4.0 mg/100 g of body weight) or corn oil (vehicle) was also given for 20 days. The weights of the rats were recorded weekly, and the influence of testosterone and pumpkin seed oil on the weight gain of the rats was examined. On day 21, rats were sacrificed, and the prostate was removed, cleaned, and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. Neither testosterone nor pumpkin seed oil had any significant influence on the weight gain of the rats. Testosterone significantly increased prostate size ratio (P < .05), and this induced increase was inhibited in rats fed with pumpkin seed oil at 2.0 mg/100 g of body weight. The protective effect of pumpkin seed oil was significant at the higher pumpkin seed oil dose (P < .02). We conclude pumpkin seed oil can inhibit testosterone-induced hyperplasia of the prostate and therefore may be beneficial in the management of benign prostatic hyperplasia.

  20. Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats

    PubMed Central

    Chin, Kok-Yong; Ima-Nirwana, Soelaiman

    2014-01-01

    Background Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a testosterone-deficient osteoporotic rat model. Methods Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined. Results There were significant degenerative changes in structural indices in the orchidectomized group (P<0.05), but no significant changes in dynamic indices, bone remodeling markers, or gene expression (P>0.05) when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05) and significantly increased expression of bone formation genes (P<0.05). Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05). Conclusion AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration. PMID:25120355

  1. Effects of methotrexate on serum testosterone level in sleep deprived male Wistar rats.

    PubMed

    Akindele, O O; Kunle-Alabi, O T; Oghenetega, B O; Adeyemi, D H; Raji, Y

    2015-06-01

    Sleep deprivation has been reported to decrease testosterone levels but the mechanism remains unclear. Studies have shown that sleep deprivation increases interleukin 1 beta (IL-1β), a pro-inflammatory cytokine and that increased IL-1β levels cause reductions in Leydig cell production of testosterone. This study was therefore designed to determine the effects of methotrexate, an IL-1β blocker on serum testosterone levels in sleep deprived male Wistar rats. Twenty male Wistar rats were randomly assigned into four groups (n = 5); group I (Control) received the vehicle (1% tween 80 solution); group II (methotrexate) received 0.5 mg/kg body weight methotrexate; group III (SD) was sleep deprived and received the vehicle; group IV (SD+Methotrexate) was sleep deprived and received 0.5 mg/kg body weight methotrexate. Sleep deprivation was induced using the modified multiple platform technique for 14 days. Treatments were administered twice weekly by oral gavage for 14 days. Blood was collected on day 14 and serum was obtained for analyses of testosterone, LH and FSH levels. IL-1β level and histology of the testis were also determined. Data were expressed as Mean ± SEM and analysed using ANOVA. p < 0.05 was considered significant. Serum testosterone levels were significantly decreased while testicular IL-1β was increased in SD and SD+Methotrexate compared with Control. FSH and LH levels were not significantly different among the groups. Results of this study suggest that reduction in serum testosterone level in sleep deprived rats is not dependent on increased level of IL-1β.

  2. Reflexive testosterone release: a model system for studying the nongenomic effects of testosterone upon male behavior.

    PubMed

    Nyby, John G

    2008-05-01

    Male mammals of many species exhibit reflexive testosterone release in mating situations. In house mice (Mus musculus), the dramatic robustness of such release, occurring primarily in response to a novel female, suggests some function. The resulting testosterone elevations typically peak during copulatory behavior and may serve to activate transitory motivational and physiological responses that facilitate reproduction. However, such a function requires that testosterone be working through either nongenomic, or very quick genomic, mechanisms. The first part of the review describes reflexive sex hormone release in house mice. The second part summarizes research implicating testosterone's fast actions in affecting anxiety, reward, learning, analgesia, and penile reflexes in rodents, all of which could optimize male mating success. The review concludes with a speculative model of how spontaneous and reflexive hormone release might interact to regulate reproductive behavior and why mice appear to be an ideal species for examining testosterone's quick effects.

  3. Testosterone replacement therapy: improved sexual desire and erectile function in men with type 2 diabetes following a 30-week randomized placebo-controlled study.

    PubMed

    Hackett, G; Cole, N; Saghir, A; Jones, P; Strange, R C; Ramachandran, S

    2017-09-01

    Although testosterone replacement treatment (TRT) can improve sexual function in many hypogonadal (HG) men with type 2 diabetes (T2DM), some show either no improvement or only in a limited number of domains. Indeed, it is often difficult for the clinician to offer an indication of the likely efficacy of TRT as little data exist on the proportion of TRT-treated men who will demonstrate improvement in domains such as sexual desire (SxD) and erectile function (EF). We describe in men with T2DM: firstly, the likelihood of improved sexual desire (SxD) and erectile function (EF) following TRT at various time points, and secondly, if probability of SxD change predicted likelihood of subsequent EF change. During a 30-week randomized controlled study of testosterone undecanoate (TU), 199 T2DM men with HG (189 men completing) identified from primary care registers (placebo (P): 107, TU: 92) were stratified using baseline total testosterone (TT)/free testosterone (FT) into Mild (TT 8.1-12 nmol/L or FT 0.18-0.25 nmol/L) and Severe HG groups (TT ≤8 nmol/L and FT ≤0.18 nmol/L) and placebo (P)- and TU-treated groups. Associations between TU, SxD and EF were investigated using chi-square and logistic regression analysis. The proportion of men with improved SxD after 6 weeks and EF improvement after 30 weeks was significantly higher following TU treatment compared to P, this particularly evident in Severe HG men. Changes in SxD and EF were significantly associated in all groups. Logistic regression showed that SxD change at 6 weeks predicted of EF change after 30 weeks. Our study confirms TRT leads to changes in SxD and EF at different time points and suggests SxD and EF changes are related. SxD change after 6 weeks predicting EF change at 30 weeks is possibly a useful clinical finding. © 2017 American Society of Andrology and European Academy of Andrology.

  4. Testosterone, cardiovascular risk, and hormonophobia.

    PubMed

    Morgentaler, Abraham

    2014-06-01

    A public outcry against testosterone (T) therapy has suddenly occurred based on two reports suggesting treatment was associated with increased cardiovascular (CV) risks. To analyze scientific and social bases for concerns regarding T therapy. Analysis of recent articles regarding CV risks with T and comparison with events surrounding publication of results of the Women's Health Initiative in 2002. In the first study, the percentage of individuals with an adverse event was lower by half in men who received T compared with untreated men (10.1% vs. 21.2%). However, an opposite conclusion was reached via complex statistics. The second study reported minor increased rate of nonfatal myocardial infarction (MI) up to 90 days after receiving a T prescription compared with the prior 12 months. However, there was no control group, so it is unknown whether this MI rate was increased, reduced, or unchanged compared with untreated men. Neither study provided substantive evidence of risk, yet these were lauded as proof of dangers, despite a substantial literature to the contrary. Similar events followed the publication of the Women's Health Initiative in 2002 when a media frenzy over increased risks with female hormone replacement therapy obscured the fact that the reported excess risk was clinically meaningless, at two events per 1,000 person-years. Stakeholders driving concerns regarding hormone risks are unlikely to be clinicians with real-world patient experience. The use of weak studies as proof of danger indicates that cultural (i.e., nonscientific) forces are at play. Negative media stories touting T's risks appear fueled by antipharma sentiment, anger against aggressive marketing, and antisexuality. This stance is best described as "hormonophobia." As history shows, evidence alone may be insufficient to alter a public narrative. The true outrage is that social forces and hysteria have combined to deprive men of a useful treatment without regard for medical science.

  5. Testosterone, territoriality, and the 'home advantage'.

    PubMed

    Neave, Nick; Wolfson, Sandy

    2003-02-01

    The consistently better performance seen by teams in various sporting contexts when playing at home is referred to as the 'home advantage'. Various explanations have been put forward to account for this robust phenomenon, though none has yet focussed on possible hormonal factors. In an initial study, we showed that salivary testosterone levels in soccer players were significantly higher before a home game than an away game.In a second study involving a different group of soccer players, this finding was replicated over two home games, two away games, and three training sessions. Perceived rivalry of the opposing team was important as testosterone levels were higher before playing an 'extreme' rival than a 'moderate' rival. Self-reported measures of mood in both studies were not linked to testosterone level. The present results corroborate and extend earlier findings on the relationships between testosterone, territoriality, and dominance in human competitive encounters and further suggest an important role for testosterone in the home advantage seen in various team sports.

  6. Prenatal Testosterone and Preschool Disruptive Behavior Disorders.

    PubMed

    Roberts, Bethan A; Martel, Michelle M

    2013-11-01

    Disruptive Behaviors Disorders (DBD), including Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD), are fairly common and highly impairing childhood behavior disorders that can be diagnosed as early as preschool. Prenatal exposure to testosterone may be particularly relevant to these early-emerging DBDs that exhibit a sex-biased prevalence rate favoring males. The current study examined associations between preschool DBD symptom domains and prenatal exposure to testosterone measured indirectly via right 2D:4D finger-length ratios. The study sample consisted of 109 preschool-age children between ages 3 and 6 (64% males;72% with DBD) and their primary caregivers. Primary caregivers completed a semi-structured interview (i.e., Kiddie Disruptive Behavior Disorder Schedule), as well as symptom questionnaires (i.e., Disruptive Behavior Rating Scale, Peer Conflict Scale); teachers and/or daycare providers completed symptom questionnaires and children provided measures of prenatal testosterone exposure, measured indirectly via finger-length ratios (i.e., right 2D:4D). Study results indicated a significant association of high prenatal testosterone (i.e., smaller right 2D:4D) with high hyperactive-impulsive ADHD symptoms in girls but not boys, suggesting that the effect may be driven by, or might only exist in, girls. The present study suggests that prenatal exposure to testosterone may increase risk for early ADHD, particularly hyperactivity-impulsivity, in preschool girls.

  7. Prenatal Testosterone and Preschool Disruptive Behavior Disorders

    PubMed Central

    Roberts, Bethan A.; Martel, Michelle M.

    2013-01-01

    Disruptive Behaviors Disorders (DBD), including Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD), are fairly common and highly impairing childhood behavior disorders that can be diagnosed as early as preschool. Prenatal exposure to testosterone may be particularly relevant to these early-emerging DBDs that exhibit a sex-biased prevalence rate favoring males. The current study examined associations between preschool DBD symptom domains and prenatal exposure to testosterone measured indirectly via right 2D:4D finger-length ratios. The study sample consisted of 109 preschool-age children between ages 3 and 6 (64% males;72% with DBD) and their primary caregivers. Primary caregivers completed a semi-structured interview (i.e., Kiddie Disruptive Behavior Disorder Schedule), as well as symptom questionnaires (i.e., Disruptive Behavior Rating Scale, Peer Conflict Scale); teachers and/or daycare providers completed symptom questionnaires and children provided measures of prenatal testosterone exposure, measured indirectly via finger-length ratios (i.e., right 2D:4D). Study results indicated a significant association of high prenatal testosterone (i.e., smaller right 2D:4D) with high hyperactive-impulsive ADHD symptoms in girls but not boys, suggesting that the effect may be driven by, or might only exist in, girls. The present study suggests that prenatal exposure to testosterone may increase risk for early ADHD, particularly hyperactivity-impulsivity, in preschool girls. PMID:25598567

  8. Testosterone replacement therapy in obese males.

    PubMed

    Drewa, Tomasz; Olszewska-Słonina, Dorota; Chlosta, Piotr

    2011-01-01

    Controversy surrounds testosterone replacement therapy in obese ageing due to no generally accepted lower limits of normal testosterone level and high prevalence of hypogonadal symptoms in the ageing male population and the non-specific nature of these symptoms. Late onset hypogonadism is a clinical and biochemical syndrome associated with advancing age, often coexisting with obesity and metabolic syndrome. High fat and carbohydrates (fructose) consumption is responsible for development of obesity and metabolic syndrome which is one of risk factors for hypogonadism in older men. High fructose intake has been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Obesity and lack of physical activity negatively influence testosterone level. Low testosterone level should be regarded as an effect of obesity, but reverse relationship has not been proved yet. The management of late-onset hypogonadism symptoms has to be treated by a change of a life style and prevented with healthy nutrition and physical activity. The question related to rational indications for testosterone replacement therapy in obese males seems to be still actual.

  9. Competition, testosterone, and adult neurobehavioral plasticity.

    PubMed

    Losecaat Vermeer, A B; Riečanský, I; Eisenegger, C

    2016-01-01

    Motivation in performance is often measured via competitions. Winning a competition has been found to increase the motivation to perform in subsequent competitions. One potential neurobiological mechanism that regulates the motivation to compete involves sex hormones, such as the steroids testosterone and estradiol. A wealth of studies in both nonhuman animals and humans have shown that a rise in testosterone levels before and after winning a competition enhances the motivation to compete. There is strong evidence for acute behavioral effects in response to steroid hormones. Intriguingly, a substantial testosterone surge following a win also appears to improve an individual's performance in later contests resulting in a higher probability of winning again. These effects may occur via androgen and estrogen pathways modulating dopaminergic regions, thereby behavior on longer timescales. Hormones thus not only regulate and control social behavior but are also key to adult neurobehavioral plasticity. Here, we present literature showing hormone-driven behavioral effects that persist for extended periods of time beyond acute effects of the hormone, highlighting a fundamental role of sex steroid hormones in adult neuroplasticity. We provide an overview of the relationship between testosterone, motivation measured from objective effort, and their influence in enhancing subsequent effort in competitions. Implications for an important role of testosterone in enabling neuroplasticity to improve performance will be discussed. © 2016 Elsevier B.V. All rights reserved.

  10. RigiScan data under long-term testosterone therapy: improving long-term blood circulation of penile arteries, penile length and girth, erectile function, and nocturnal penile tumescence and duration.

    PubMed

    Canguven, Onder; Talib, Raidh A; El-Ansari, Walid; Shamsoddini, Ahmed; Salman, Mahmoud; Al-Ansari, Abdulla

    2016-12-01

    Late-onset hypogonadism (LOH) presents with low serum testosterone (TT) levels and sexual and nonsexual symptoms. Erectile dysfunction affects a man's self-esteem and as a result partner relationship and quality of life. To investigate the andrological clinical profile outcomes of testosterone therapy (TTh) in men (n = 88) with symptomatic LOH complaints and symptoms. Erectile function was assessed using the International Index of Erectile Function-5 questionnaire at baseline and at 6 and 12 months of TTh. In addition, penile length was measured at baseline and 12 months. We also evaluated nocturnal penile tumescence (NPT, using RigiScan) and blood flow of cavernous arteries (penile Doppler ultrasonography) at baseline and 12 months of TT. Eighty-eight LOH men (Mage 51.1 years) with erectile dysfunction, all with serum TT <10.4 nmol/L before TTh. Patients received intramuscular long-acting testosterone undecanoate for 12 months. Following TTh, in all patients, serum TT levels were restored within 3 months to normal levels. Compared with baseline values, erectile function significantly improved at 6 (mean score increase 1.95) and 12 months (mean score increase 2.16). No significant changes in penile length were observed. NPT significantly improved at 12 months in terms of both the frequency (mean increase 1.27 times) and duration of rigidity (mean increase 5.12 min). As regards the blood flow of the cavernous arteries, we observed a significant improvement (decrease of 1.16 cm/s) and end diastolic velocity of the penile arteries. TTh in men with LOH resulted in improvement of the erectile function, NPT, and to some extent the blood flow of the cavernous arteries.

  11. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan H.; Allen, Zachariah A.; Wallner, Kent E.

    2012-01-01

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response

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

    PubMed

    Enatsu, N; Miyake, H; Haraguchi, T; Chiba, K; Fujisawa, M

    2016-12-01

    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 12 months after the treatment with dutasteride. Patients were divided into two groups based on changes in serum testosterone after 1 month: Group A (>20% increase; n = 33) or Group B (<20% increase; n = 29). Serum free-testosterone levels were 20.4% higher after 1 month 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 12 months, 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 12 months, 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.

  13. Annatto Tocotrienol Improves Indices of Bone Static Histomorphometry in Osteoporosis Due to Testosterone Deficiency in Rats

    PubMed Central

    Chin, Kok-Yong; Abdul-Majeed, Saif; Mohd. Fozi, Nur Farhana; Ima-Nirwana, Soelaiman

    2014-01-01

    This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent. PMID:25389899

  14. Exogenous Testosterone, Finasteride and Castration Effects on Testosterone, Insulin, Zinc and Chromium in Adult Male Rats

    PubMed Central

    Yousofvand, Namdar; Zarei, Fatemeh; Ghanbari, Ali

    2013-01-01

    Background: Although effects of trace elements on secretion of sex steroids and insulin have been studied, the effects of these hormones on serum level of trace elements have been rarely investigated. The aim of the present study was to evaluate the effect of testosterone and finasteride administration and castration on serum levels of testosterone, insulin, zinc and chromium. Methods: Male adult rats (n = 32) were divided into 4 groups (n = 8). Group 1, control; Group 2, castration, castration was done at the first day of the study; Group 3, finasteride (20 mg/kg/day, dissolved in drinking water) and Group 4, testosterone (5 mg/kg/day, i.p.). At the end of the period of the study (35 days), serum testosterone, insulin, zinc and chromium levels were determined in the blood samples collected directly from the right atrium of the heart of the animals. Results: The data indicated that the serum levels of testosterone, insulin and zinc were significantly increased (P<0.01) in testosterone-administrated and finasteride groups, but the level of chromium was decreased in both groups (P<0.01). Castrated group had the lowest serum levels of testosterone, insulin and zinc (P<0.05). Also, the levels of serum chromium in this group were increased. Conclusion: The study demonstrates that testosterone and finasteride increases insulin and zinc levels and decreases chromium levels in the serum of male adult rats. According to these data, it seems that testosterone may affect glucose cycle through effect on serum insulin levels and trace elements such as zinc and chromium. PMID:23279835

  15. Exogenous testosterone, finasteride and castration effects on testosterone, insulin, zinc and chromium in adult male rats.

    PubMed

    Yousofvand, Namdar; Zarei, Fatemeh; Ghanbari, Ali

    2013-01-01

    Although effects of trace elements on secretion of sex steroids and insulin have been studied, the effects of these hormones on serum level of trace elements have been rarely investigated. The aim of the present study was to evaluate the effect of testosterone and finasteride administration and castration on serum levels of testosterone, insulin, zinc and chromium. Male adult rats (n = 32) were divided into 4 groups (n = 8). Group 1, control; Group 2, castration, castration was done at the first day of the study; Group 3, finasteride (20 mg/kg/day, dissolved in drinking water) and Group 4, testosterone (5 mg/kg/day, i.p.). At the end of the period of the study (35 days), serum testosterone, insulin, zinc and chromium levels were determined in the blood samples collected directly from the right atrium of the heart of the animals. The data indicated that the serum levels of testosterone, insulin and zinc were significantly increased (P<0.01) in testosterone-administrated and finasteride groups, but the level of chromium was decreased in both groups (P<0.01). Castrated group had the lowest serum levels of testosterone, insulin and zinc (P<0.05). Also, the levels of serum chromium in this group were increased. The study demonstrates that testosterone and finasteride increases insulin and zinc levels and decreases chromium levels in the serum of male adult rats. According to these data, it seems that testosterone may affect glucose cycle through effect on serum insulin levels and trace elements such as zinc and chromium.

  16. Gender moderates the relationship between testosterone and marital interaction.

    PubMed

    Cohan, Catherine L; Booth, Alan; Granger, Douglas A

    2003-03-01

    Higher testosterone levels are related to assertiveness and dominance. Given the relevance of those behavioral correlates to spouses' daily transactions, links between testosterone levels and marital interaction were explored among 92 newlywed couples. Marital problem-solving and social support transactions were assessed, and saliva was collected and assayed for testosterone. Whether marital behavior was related to husbands' and wives' testosterone levels was examined. The link between spouses' testosterone and their behavior was contingent on the partner's testosterone levels. Husbands exhibited more adaptive problem-solving behaviors and social support provision when husbands and wives were concordant for lower testosterone levels. In contrast, wives exhibited more adaptive support provision when spouses had discordant testosterone levels such that wives had higher levels and husbands had lower levels.

  17. Testosterone Therapy May Have Benefits, but Risks Too

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163696.html Testosterone Therapy May Have Benefits, But Risks Too While ... 21, 2017 TUESDAY, Feb. 21, 2017 (HealthDay News) -- Testosterone treatment can boost bone density and reduce anemia ...

  18. Effects of in vivo testosterone manipulation on ovarian morphology, follicular development, and follicle yolk testosterone in the homing pigeon.

    PubMed

    Goerlich, Vivian C; Dijkstra, Cor; Groothuis, Ton G G

    2010-07-01

    To date, our understanding of the function of testosterone in female reproductive physiology is only marginal although there are indications that testosterone is involved in modulating follicular recruitment, growth, atresia, and ovulation. Studies elevating testosterone in breeding female birds have, in most instances, found detrimental effects, such as delayed clutch initiation or decreased clutch size. In our previous study, testosterone treatment of female homing pigeons delayed clutch initiation without diminishing fecundity. In this study, we explore whether the observed effect might have been caused by testosterone influencing follicle maturation or ovulation. We implanted mature female pigeons with testosterone prior to pairing, which resulted in constant elevation of circulating testosterone concentrations within the physiological range. We killed females after they had laid the first egg and measured ovarian and follicular development. Ovarian mass and pre-hierarchical yolky follicles were not affected by the treatment; however, testosterone females produced smaller and lighter preovulatory follicles. High plasma testosterone levels at oviposition or a strong temporal increase in testosterone were negatively related to mass and diameter of second follicles. We proposed that sustained elevation of testosterone delays follicular maturation, potentially via negative feedback on the hypothalamo-pituitary-gonadal axis. Furthermore, to gain better insight into the regulation of yolk hormone acquisition, we measured testosterone concentrations in the preovulatory follicles. We found no differences between treatment groups but follicle yolk contained much higher levels of testosterone than yolk of un-incubated eggs, suggesting that hormone measurements performed after oviposition do not correctly reflect maternal allocation.

  19. Skin permeation of testosterone and its ester derivatives in rats.

    PubMed

    Kim, M K; Lee, C H; Kim, D D

    2000-04-01

    To establish the optimum conditions for improving the transdermal delivery of testosterone, we studied the relationship between the lipophilicity of testosterone ester derivatives and the rat skin permeation rate of testosterone. We performed a rat skin permeation study of testosterone and its commercially available ester derivatives, testosterone hemisuccinate, testosterone propionate and testosterone-17beta-cypionate, using an ethanol/water co-solvent system. The aqueous solubility and rat skin permeation rate of each drug, saturated in various compositions of an ethanol/water system, was determined at 37 degrees C. The aqueous solubility of testosterone and its ester derivatives increased exponentially as the volume fraction of ethanol increased up to 100% (v/v). The stability of testosterone propionate in both the skin homogenate and the extract was investigated to observe the enzymatic degradation during the skin permeation process. Testosterone propionate was found to be stable in the isotonic buffer solution and in the epidermis-side extract for 10h at 37 degrees C. However, in the skin homogenate and the dermis-side extract testosterone propionate rapidly degraded producing testosterone, implying that testosterone propionate rapidly degraded to testosterone during the skin permeation process. The steady-state permeation rates of testosterone in the ethanol/water systems increased exponentially as the volume fraction of ethanol increased, reaching the maximum value (2.69+/-0.69 microg cm(-2)h(-1)) at 70% (v/v) ethanol in water, and then decreasing with further increases in the ethanol volume fraction. However, in the skin permeation study with testosterone esters saturated in 70% (v/v) ethanol in water system, testosterone esters were hardly detected in the receptor solution, probably due to the rapid degradation to testosterone during the skin permeation process. Moreover, a parabolic relationship was observed between the permeation rate of testosterone and

  20. Testosterone nasal gel (Natesto) for hypogonadism.

    PubMed

    2015-05-11

    In one study, Natesto nasal gel administered intranasally 3 times daily was effective in raising low serum testosterone levels into the normal range in patients with hypogonadism. Whether patients will find this method of administration more acceptable than an intramuscular injection every 2-4 weeks or once-daily application to the skin remains to be determined. Based on the lack of convincing evidence of benefit in older men and concerns about its safety, the FDA has warned against using testosterone to treat hypogonadism due solely to aging.

  1. Off label therapies for testosterone replacement

    PubMed Central

    DiGiorgio, Lorenzo

    2016-01-01

    The incidence of hypogonadism has been steadily increasing over the last few years. Exogenous testosterone has been the standard treatment for hypogonadal men, but is associated with suppression of spermatogenesis as well as other possible adverse effects. There are other medications, currently considered “off label” for androgen replenishment, that exert their effect through modulation of the hypothalamic-gonadal axis. These medications increase endogenous testosterone levels and offer a different therapeutic approach. This review will focus on these alternative (off-label) therapies for androgen replacement in men. PMID:28078215

  2. Testosterone metabolism and its testosterone-dependent activation in the uropygial gland of quail.

    PubMed

    Floch, J Y; Morfin, R F; Daniel, J Y; Floch, H H

    1988-01-01

    The in vitro metabolism in the uropygial gland of the male quail results into large yields of 5 beta-reduced and/or 17 alpha-hydroxylated metabolites. This metabolism was studied in glands of sexually quiescent quails five days after a single intra-muscular injection of testosterone to the birds. This treatment led to an increased production of inactive metabolites (epitestosterone and its 5 beta-reduced metabolites) and to a decrease of unmetabolized testosterone. Thus testosterone controls its own metabolism and by this way means to modulate its action in the uropygial gland of quail.

  3. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  4. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  5. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  6. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  7. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  8. Testosterone metabolism in the uropygial gland of the quail.

    PubMed

    Floch, J Y; Morfin, R; Picart, D; Daniel, J Y; Floch, H H

    1985-05-01

    The metabolism of testosterone in the uropygial gland of the quail principally results in the production of 17 alpha, 5 beta derivatives. Moreover, an unusually small amount of testosterone is converted to 5 alpha-dihydrotestosterone. These results question the role played by intracellular 5 alpha-reduction in the response of the gland to testosterone stimulation.

  9. Testosterone deficiency syndrome: benefits, risks, and realities associated with testosterone replacement therapy.

    PubMed

    Hassan, Jacob; Barkin, Jack

    2016-02-01

    Testosterone deficiency syndrome, which has sometimes been termed age-related or late-onset hypogonadism, is a syndrome characterized by both clinical manifestations as well as a biochemical deficiency of testosterone. This condition is associated with considerable morbidity and mortality, accounting for billions of dollars in health care costs. There is some evidence that suggests that restoring testosterone levels in these individuals may help to manage or delay progression of the associated morbidities. Furthermore, despite controversies in the literature and media, testosterone replacement has proven to be quite safe in most men with minimal if any adverse effects when dosing to achieve the eugonadal range. It is nevertheless very important for clinicians to be aware of the possible risks and contraindications of treatment to ensure proper patient selection and appropriate monitoring.

  10. Techniques to measure testosterone in the elderly.

    PubMed

    Klee, G G; Heser, D W

    2000-01-01

    In today's clinical and research settings, there is an unfortunate lack of consistency for the term "measuring testosterone status." This term is often used to refer to a measure of biologic androgen activity rather than the specific measurement of the chemical concentration of the testosterone steroid molecule. Even the measurements of chemical concentrations show considerable methodologic differences. This is true for measurements in elderly men, as well as in other populations, including women. All of the current methods for measuring total testosterone have limitations, especially with regard to low concentrations. In addition, unresolved questions concerning the active form of the hormone preclude definitive determination of which form of testosterone and which other androgen hormones are best suited for measuring androgen activity. When measurement techniques are compared, the numbers correlate with each other but certainly do not represent the same value. There is a need for a consensus as to which forms of hormones should be measured to best assess androgen status, and there is a need to standardize the procedures used to measure these hormones.

  11. Testosterone and Aggression: Berthold, Birds and Beyond

    PubMed Central

    Soma, K. K.

    2010-01-01

    Berthold’s classic study of domesticated roosters in 1849 demonstrated that testicular secretions are necessary for the normal expression of aggressive behaviour. Although this conclusion is undoubtedly correct, field studies of wild songbirds have yielded important modifications and limitations of Berthold’s original hypothesis. For example, studies of the North American song sparrow (Melospiza melodia) during the breeding season reveal that not only does testosterone increase aggression, but aggressive interactions also increase plasma testosterone levels. Furthermore, in winter, nonbreeding song sparrows have low plasma testosterone levels but are very aggressive, and castration of nonbreeding song sparrows does not decrease aggression. Interestingly, an aromatase inhibitor (fadrozole) does decrease male aggression in the nonbreeding season, and the effects of fadrozole can be rescued with oestradiol. In winter, dehydroepiandrosterone (DHEA) from the periphery can be metabolised within the brain to supply oestradiol to specific neural circuits. Additionally, oestradiol might be synthesised de novo from cholesterol entirely within the brain. These mechanisms may have evolved to avoid the ‘costs’ of circulating testosterone in the nonbreeding season. Recent studies in tropical birds, hamsters, and humans suggest that these neuroendocrine mechanisms are important for the control of aggression in many vertebrate species. PMID:16774503

  12. Pharmacology of testosterone replacement therapy preparations

    PubMed Central

    Shoskes, Jennifer J.; Wilson, Meghan K.

    2016-01-01

    The goal of testosterone replacement therapy (TRT) is to return serum testosterone levels to within physiologic range and improve symptoms in hypogonadal men. Some of the symptoms aimed to improve upon include decreased libido, erectile dysfunction, infertility, hot flashes, depressed mood, and loss of muscle mass or hair. Clinical use of testosterone for replacement therapy began approximately 70 years ago. Over the decades, numerous preparations and formulations have been developed primarily focusing on different routes of delivery and thus pharmacokinetics (PKs). Currently the routes of delivery approved for use by the United States Food and Drug Administration encompasses buccal, nasal, subdermal, transdermal, and intramuscular (IM). Many factors must be considered when a clinician is choosing the most correct formulation for a patient. As this decision depends highly on the patient, active patient participation is important for effective selection. The aim of this review is to describe and compare all testosterone preparations currently available and approved by the United States Food and Drug Administration. Areas of focus will include pharmacology, PKs, adverse effects, and specifics related to individual delivery routes. PMID:28078214

  13. Wide variability in laboratory reference values for serum testosterone.

    PubMed

    Lazarou, Stephen; Reyes-Vallejo, Luis; Morgentaler, Abraham

    2006-11-01

    The laboratory determination of testosterone levels consistent with a diagnosis of hypogonadism is complicated by the availability of multiple testosterone assays and varying reference ranges. To assess current laboratory practices regarding availability of testosterone assays and use of reference values. A telephone survey of 12 academic, 12 community medical laboratories, and one national laboratory. Types of androgen assays offered and determination of reference values. All of the academic and eight of the community centers performed total testosterone testing. Free testosterone was performed in-house by six of the 12 academic and one community center. Testing for bioavailable testosterone, free androgen index, and percent free testosterone was performed in-house by no more than two centers. There were eight and four different assays used for total and free testosterone, respectively. One national laboratory offered equilibrium dialysis measurement of free testosterone. Of the 25 labs, there were 17 and 13 different sets of reference values for total and free testosterone, respectively. The low reference value for total testosterone ranged from 130 to 450 ng/dL (350% difference), and the upper value ranged from 486 to 1,593 ng/dL (325% difference). Age-adjusted reference values were applied in four centers for total testosterone and in seven labs for free testosterone. All reference values were based on a standard statistical model without regard for clinical aspects of hypogonadism. Twenty-three of the 25 lab directors responded that clinically relevant testosterone reference ranges would be preferable to current standards. Laboratory reference values for testosterone vary widely, and are established without clinical considerations.

  14. Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats.

    PubMed

    Yang, Bi-Cheng; Jin, Li-Li; Yang, Yi-Fang; Li, Kun; Peng, Dan-Ming

    2014-07-01

    Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape pollen is an apicultural product that is composed of nutritionally valuable and biologically active substances. The aim of the present study was to investigate the protective effect of rape pollen supercritical CO2 fluid extract (SFE-CO2) in BPH development using a testosterone-induced BPH rat model. BPH was induced in the experimental groups by daily subcutaneous injections of testosterone for a period of 30 days. Rape pollen SFE-CO2 was administered daily by oral gavage concurrently with the testosterone injections. Animals were sacrificed at the scheduled termination and the prostates were weighed and subjected to histopathological examination. Testosterone, dihydrotestosterone (DHT), 5α-reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced animals exhibited an increase in prostate weight with increased testosterone, DHT, 5α-reductase and COX-2 expression levels. However, rape pollen SFE-CO2 treatment resulted in significant reductions in the prostate index and testosterone, DHT, 5α-reductase and COX-2 levels compared with those in BPH-induced animals. Histopathological examination also demonstrated that rape pollen SFE-CO2 treatment suppressed testosterone-induced BPH. These observations indicate that rape pollen SFE-CO2 inhibits the development of BPH in rats and these effects are closely associated with reductions in DHT, 5α-reductase and COX-2 levels. Therefore, the results of the present study clearly indicate that rape pollen SFE-CO2 extract may be a useful agent in BPH treatment.

  15. Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats

    PubMed Central

    YANG, BI-CHENG; JIN, LI-LI; YANG, YI-FANG; LI, KUN; PENG, DAN-MING

    2014-01-01

    Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape pollen is an apicultural product that is composed of nutritionally valuable and biologically active substances. The aim of the present study was to investigate the protective effect of rape pollen supercritical CO2 fluid extract (SFE-CO2) in BPH development using a testosterone-induced BPH rat model. BPH was induced in the experimental groups by daily subcutaneous injections of testosterone for a period of 30 days. Rape pollen SFE-CO2 was administered daily by oral gavage concurrently with the testosterone injections. Animals were sacrificed at the scheduled termination and the prostates were weighed and subjected to histopathological examination. Testosterone, dihydrotestosterone (DHT), 5α-reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced animals exhibited an increase in prostate weight with increased testosterone, DHT, 5α-reductase and COX-2 expression levels. However, rape pollen SFE-CO2 treatment resulted in significant reductions in the prostate index and testosterone, DHT, 5α-reductase and COX-2 levels compared with those in BPH-induced animals. Histopathological examination also demonstrated that rape pollen SFE-CO2 treatment suppressed testosterone-induced BPH. These observations indicate that rape pollen SFE-CO2 inhibits the development of BPH in rats and these effects are closely associated with reductions in DHT, 5α-reductase and COX-2 levels. Therefore, the results of the present study clearly indicate that rape pollen SFE-CO2 extract may be a useful agent in BPH treatment. PMID:24944593

  16. Oxytocin, testosterone, and human social cognition.

    PubMed

    Crespi, Bernard J

    2016-05-01

    I describe an integrative social-evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co-opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness-enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness-reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self-oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under-developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively 'hyper-developed' social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint

  17. Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective

    PubMed Central

    Mosli, Hala H.; Esmat, Ahmed; Atawia, Reem T.; Shoieb, Sherif M.; Mosli, Hisham A.; Abdel-Naim, Ashraf B.

    2015-01-01

    Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight & prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone–induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation. PMID:26492952

  18. Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

    PubMed

    Ponzetto, Federico; Mehl, Florence; Boccard, Julien; Baume, Norbert; Rudaz, Serge; Saugy, Martial; Nicoli, Raul

    2016-01-01

    The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control

  19. Transmucosal delivery of testosterone in rabbits using novel bi-layer mucoadhesive wax-film composite disks.

    PubMed

    Jay, Steven; Fountain, William; Cui, Zhengrong; Mumper, Russell J

    2002-09-01

    Testosterone exhibits very low oral bioavailability because of its low aqueous solubility and extensive first-pass metabolism. The purpose of this study was to develop a novel bi-layer mucoadhesive wax-film composite (WFC), and to test the relative bioavailability of testosterone via the buccal route in rabbits. The release rate of testosterone from optimal WFCs (3/8-in. diameter) per unit surface area was 5.6 microg x cm(2) x mL(-1) x min(-1) and was zero-order. Bi-layer WFCs (average weight of 14 +/- 2.6 mg and thickness of 186 +/- 34 microns) containing 4 mg of testosterone were applied to the buccal pouch of anesthetized New Zealand white rabbits. Rabbits (n = 3) injected intravenously had C(max) and area under the curve values of 1200 +/- 46 ng/mL, and 48,227 +/- 12,995 ng x min/mL, respectively. Rabbits (n = 3) dosed via the buccal pouch had C(max), T(max), and area under the curve values of 127 +/- 13 ng/mL, 200 +/- 35 min, and 24,221 +/- 1543 ng x min/mL. The relative bioavailability for rabbits treated with the WFC was 50.2 +/- 3.2% with a coefficient of variation of 6.4%. It was concluded that these bi-layer mucoadhesive WFCs disks could deliver physiologically relevant amounts of insoluble drugs such as testosterone across the buccal mucosa.

  20. Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism.

    PubMed

    Giagulli, V A; Carbone, M D; Ramunni, M I; Licchelli, B; De Pergola, G; Sabbà, C; Guastamacchia, E; Triggiani, V

    2015-11-01

    The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol

  1. Effect of Exercise Training and Testosterone Replacement on Skeletal Muscle Wasting in Patients With Heart Failure With Testosterone Deficiency.

    PubMed

    Dos Santos, Marcelo R; Sayegh, Ana L C; Bacurau, Aline V N; Arap, Marco A; Brum, Patrícia C; Pereira, Rosa M R; Takayama, Liliam; Barretto, Antônio C P; Negrão, Carlos E; Alves, Maria Janieire de Nazaré Nunes

    2016-05-01

    To examine whether combined testosterone replacement and exercise training (ET) therapies would potentiate the beneficial effects of isolated therapies on neurovascular control and muscle wasting in patients with heart failure (HF) with testosterone deficiency. From January 10, 2010, through July 25, 2013, 39 male patients with HF, New York Heart Association functional class III, total testosterone level less than 249 ng/dL (to convert to nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L were randomized to training (4-month cycloergometer training), testosterone (intramuscular injection of testosterone undecylate for 4 months), and training + testosterone groups. Muscle sympathetic nerve activity was measured using microneurography, forearm blood flow using plethysmography, body composition using dual X-ray absorptiometry, and functional capacity using cardiopulmonary test. Skeletal muscle biopsy was performed in the vastus lateralis. Muscle sympathetic nerve activity decreased in ET groups (training, P<.01; training + testosterone, P<.01), whereas no changes were observed in the testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean mass increased in ET groups (training, P<.01; training + testosterone, P<.01), whereas lean mass decreased in the testosterone group (P<.01). The response of cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in the training + testosterone group as compared with the isolated testosterone group. Our findings provide evidence for a superior effect of combined ET and testosterone replacement therapies on muscle sympathetic nerve activity, muscle wasting, and functional capacity in patients with HF with testosterone deficiency. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  2. Testosterone and its dimers alter tRNA morphology.

    PubMed

    Chanphai, P; Agudelo, D; Vesper, A R; Bérubé, G; Tajmir-Riahi, H A

    2017-02-05

    The morphology of tRNA was studied upon conjugation with testosterone and its aliphatic and aromatic dimers, using multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling. Structural analysis showed that testosterone binds tRNA through A62, A64, C60, C61, C63, G51, U50 and U59 bases. The binding affinity was testosterone dimer-aromatic>testosterone dimer-aliphatic>testosterone. The steroid loading efficacy was 35-45%. Transmission electron microscopy showed major changes in tRNA morphology upon testosterone interaction with an increase in the diameter of the tRNA aggregate, indicating encapsulation of testosterone by tRNA. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The effect of pomegranate fruit extract on testosterone-induced BPH in rats.

    PubMed

    Ammar, Amr E; Esmat, Ahmed; Hassona, Mohammed D H; Tadros, Mariane G; Abdel-Naim, Ashraf B; Guns, Emma S Tomlinson

    2015-05-01

    Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in the pathology of BPH. Pomegranate contains a variety of polyphenolic compounds that have been studied in a medley of diseases for their anti-oxidant, anti-inflammatory and pro-apoptotic properties. Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on the development of BPH using a testosterone-induced BPH model in rats. A total of 48 rats were randomly divided into six groups of eight, one group served as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four groups, three of them received PFE by oral gavage daily at doses of 25, 50, and 100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg without induction of BPH. PFE at a dose of 100 mg/kg was the most effective in decreasing testosterone-induced increase in prostate weight, prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68% respectively and in preventing the accompanying histological changes. In the BPH model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and 0.88 of the control group values respectively, and significantly increased MDA by >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values respectively, whereas MDA was significantly decreased by 72% compared with the testosterone treated group. In addition to this, at the range of doses studied, PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index. The current findings elucidate the effectiveness of PFE in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its anti-oxidant, anti-inflammatory, and pro-apoptotic properties. © 2015 Wiley Periodicals, Inc.

  4. Genetic Determinants of Serum Testosterone Concentrations in Men

    PubMed Central

    Maggio, Marcello; Coviello, Andrea D.; Ferrucci, Luigi; Heier, Margit; Hofman, Albert; Holliday, Kate L.; Jansson, John-Olov; Kähönen, Mika; Karasik, David; Karlsson, Magnus K.; Kiel, Douglas P.; Liu, Yongmei; Ljunggren, Östen; Lorentzon, Mattias; Lyytikäinen, Leo-Pekka; Meitinger, Thomas; Mellström, Dan; Melzer, David; Miljkovic, Iva; Nauck, Matthias; Nilsson, Maria; Penninx, Brenda; Pye, Stephen R.; Vasan, Ramachandran S.; Reincke, Martin; Rivadeneira, Fernando; Tajar, Abdelouahid; Teumer, Alexander; Uitterlinden, André G.; Ulloor, Jagadish; Viikari, Jorma; Völker, Uwe; Völzke, Henry; Wichmann, H. Erich; Wu, Tsung-Sheng; Zhuang, Wei Vivian; Ziv, Elad; Wu, Frederick C. W.; Raitakari, Olli; Eriksson, Anna; Bidlingmaier, Martin; Harris, Tamara B.; Murray, Anna; de Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender; Vandenput, Liesbeth; Haring, Robin

    2011-01-01

    Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. PMID:21998597

  5. Testosterone levels and fecundity in the hermaphroditic aquatic snail Lymnaea stagnalis exposed to testosterone and endocrine disruptors.

    PubMed

    Giusti, Arnaud; Ducrot, Virginie; Joaquim-Justo, Célia; Lagadic, Laurent

    2013-08-01

    Endocrine disruptors are known to alter endogenous free and esterified levels of androgenic and estrogenic steroid hormones in aquatic mollusks. The origin of steroids in these animals, however, remains controversial. In the present study, free and esterified testosterone concentrations were measured in the hermaphroditic aquatic gastropod Lymnaea stagnalis exposed to molecules known for their androgenic (testosterone and tributyltin), anti-androgenic (cyproterone-acetate), and estrogenic (chlordecone) properties, by reference to their mode of action in vertebrates. In parallel, snail oviposition and fecundity were followed over a 21-d exposure period. Testosterone exposure resulted in increased esterified testosterone levels, whereas free testosterone concentrations remained stable. In contrast, cyproterone-acetate significantly increased the free form of testosterone with no changes in the esterified form, whereas chlordecone showed a tendency to reduce (though not significantly) esterified testosterone concentrations without changing free testosterone levels. Finally, tributyltin did not alter testosterone homeostasis. The production of egg clutches and eggs was significantly reduced only in the snails exposed to the highest concentrations of chlordecone (19.6 µg/L) and tributyltin (94.2 ng Sn/L). Overall, the present study demonstrates that uptake of testosterone from the exposure medium occurs in L. stagnalis. Moreover, it shows that cyproterone-acetate and, to a lesser extent, chlordecone can alter endogenous testosterone levels in this freshwater snail. However, the relationship between hormonal changes and snail reproduction has not been established. Environ Toxicol Chem 2013;32:1740-1745. © 2013 SETAC.

  6. Testosterone metabolism in the estuarine mysid neomysis integer (Crustacea; Mysidacea): identification of testosterone metabolites and endogenous vertebrate-type steroids.

    PubMed

    Verslycke, Tim; De Wasch, Katia; De Brabander, Hubert F; Janssen, Colin R

    2002-04-01

    Testosterone metabolism by Neomysis integer (Crustacea; Mysidacea) was assessed to obtain initial data on its metabolic capacity. N. integer were exposed to both testosterone and [(14)C]testosterone. Identification of testosterone metabolites and endogenous steroids was performed using thin-layer chromatography and liquid chromatography with multiple mass spectrometry. Endogenous production of testosterone in mysids was detected for the first time. N. integer were exposed to testosterone and metabolized administered testosterone extensively. At least 11 polar testosterone metabolites (R(f,metabolite) < R(f,testosterone)), androstenedione, dihydrotestosterone, and testosterone were produced in vivo by N. integer. A sex-specific testosterone metabolism was also observed, although this observation requires further confirmation. The anabolic steroid beta-boldenone was also identified for the first time in invertebrates. The metabolic pathway leading to the formation of beta-boldenone remains unknown, since the steroidal precursor androstadienedione could not be detected. These results reveal interesting similarities in enzyme systems in invertebrate and vertebrate species. Alterations in steroid hormone metabolism may be used as a new biomarker for the effects of endocrine disruptors in invertebrates.

  7. Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone

    PubMed Central

    Budoff, Matthew J.; Ellenberg, Susan S.; Lewis, Cora E.; Mohler, Emile R.; Wenger, Nanette K.; Bhasin, Shalender; Barrett-Connor, Elizabeth; Swerdloff, Ronald S.; Stephens-Shields, Alisa; Cauley, Jane A.; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Gill, Thomas M.; Matsumoto, Alvin M.; Molitch, Mark E.; Nakanishi, Rine; Nezarat, Negin; Matsumoto, Suguru; Hou, Xiaoling; Basaria, Shehzad; Diem, Susan J.; Wang, Christina; Cifelli, Denise; Snyder, Peter J.

    2017-01-01

    IMPORTANCE Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. OBJECTIVE To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. DESIGN, SETTING, AND PARTICIPANTS Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. INTERVENTION Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES The primary outcome was non calcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). RESULTS Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81%were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95%CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased

  8. Physiological levels of testosterone kill salmonid leukocytes in vitro

    USGS Publications Warehouse

    Slater, C.H.; Schreck, C.B.

    1997-01-01

    Adult spring chinook salmon (Oncorhynchus tshawytscha) elaborate high plasma concentrations of testosterone during sexual maturation, and these levels of testosterone have been shown to reduce the salmonid immune response in vitro. Our search for the mechanism of testosterone's immunosuppressive action has led to the characterization of an androgen receptor in salmonid leukocytes. In the present study we examined the specific effects that testosterone had on salmonid leukocytes. Direct counts of viable leukocytes after incubation with and without physiological levels of testosterone demonstrate a significant loss of leukocytes in cultures exposed to testosterone. At least 5 days of contact with testosterone was required to produce significant immunosuppression and addition of a 'conditioned media' (supernatant from proliferating lymphocytes not exposed to testosterone) did not reverse the immunosuppressive effects of testosterone. These data lead us to conclude that testosterone may exert its immunosuppressive effects by direct action on salmonid leukocytes, through the androgen receptor described, and that this action leads to the death of a significant number of these leukocytes.

  9. Testosterone-Related Cortical Maturation Across Childhood and Adolescence

    PubMed Central

    Nguyen, Tuong-Vi; McCracken, James; Ducharme, Simon; Botteron, Kelly N.; Mahabir, Megan; Johnson, Wendy; Israel, Mimi; Evans, Alan C.; Karama, Sherif

    2013-01-01

    Neuroendocrine theories of brain development hold testosterone as the predominant factor mediating sex-specific cortical growth and the ensuing lateralization of hemispheric function. However, studies to date have focussed on prenatal testosterone rather than pubertal changes in testosterone. Yet, animal studies have shown a high density of androgen-sensitive receptors in multiple key cortical areas, and puberty is known to coincide with both a significant rise in testosterone and the emergence of behavioral sex differences, suggesting peripubertal influences of testosterone on brain development. Here, we used linear mixed models to examine sex-specific cortical maturation associated with changes in testosterone levels in a longitudinal sample of developmentally healthy children and adolescents. A significant “sex by age by testosterone” interaction on cortical thickness (CTh) involving widespread areas of the developing brain was found. Testosterone levels were associated with CTh changes in regions of the left hemisphere in males and of the right hemisphere in females. In both sexes, the relationship between testosterone and CTh varied across the age span. These findings show the association between testosterone and CTh to be complex, highly dynamic, and to vary, depending on sex and age; they also suggest sex-related hemispheric lateralization effects of testosterone in humans. PMID:22617851

  10. The TRPM8 Protein Is a Testosterone Receptor

    PubMed Central

    Asuthkar, Swapna; Demirkhanyan, Lusine; Sun, Xiaohui; Elustondo, Pia A.; Krishnan, Vivek; Baskaran, Padmamalini; Velpula, Kiran Kumar; Thyagarajan, Baskaran; Pavlov, Evgeny V.; Zakharian, Eleonora

    2015-01-01

    Testosterone is a key steroid hormone in the development of male reproductive tissues and the regulation of the central nervous system. The rapid signaling mechanism induced by testosterone affects numerous behavioral traits, including sexual drive, aggressiveness, and fear conditioning. However, the currently identified testosterone receptor(s) is not believed to underlie the fast signaling, suggesting an orphan pathway. Here we report that an ion channel from the transient receptor potential family, TRPM8, commonly known as the cold and menthol receptor is the major component of testosterone-induced rapid actions. Using cultured and primary cell lines along with the purified TRPM8 protein, we demonstrate that testosterone directly activates TRPM8 channel at low picomolar range. Specifically, testosterone induced TRPM8 responses in primary human prostate cells, PC3 prostate cancer cells, dorsal root ganglion neurons, and hippocampal neurons. Picomolar concentrations of testosterone resulted in full openings of the purified TRPM8 channel in planar lipid bilayers. Furthermore, acute applications of testosterone on human skin elicited a cooling sensation. Our data conclusively demonstrate that testosterone is an endogenous and highly potent agonist of TRPM8, suggesting a role of TRPM8 channels well beyond their well established function in somatosensory neurons. This discovery may further imply TRPM8 channel function in testosterone-dependent behavioral traits. PMID:25480785

  11. ALPK1 affects testosterone mediated regulation of proinflammatory cytokines production.

    PubMed

    Kuo, Tzer-Min; Yeh, Kun-Tu; Hsu, Hui-Ting; Chiang, Shang-Lun; Chang, Jan-Gowth; Huang, Chung-Ming; Tu, Hung-Pin; Liu, Chiu-Shong; Ko, Ying-Chin

    2015-11-01

    Alpha-protein kinase 1, also known as alpha-kinase 1 (ALPK1), is associated with chronic kidney disease (CKD), myocardial infarction, gout and type 2 diabetes mellitus (DM). In addition to having an inductive effect on the proinflammatory cytokines in monocytic THP1 cells, ALPK1 is expressed abundantly in the mouse testes. Low testosterone levels are commonly associated with arthritis, CKD, type 2 DM, cardiovascular disease and inflammation. The testosterone's anti-inflammatory effect has been demonstrated to reduce proinflammatory cytokines and adhesion molecules. In this study, we found that ALPK1 transgenic mice showed lower levels of testosterone in both the testes and the serum. Decreasing endogenous ALPK1 enhanced testosterone levels and transcripts of testosterone-regulated genes (P450scc, 3beta-HSD, P450C17, 17beta-HSD, StAR, and INSL3) in TM3 Leydig cells. In contrast, increasing testosterone decreased ALPK1 in both TM3 and monocytic THP1 cells. This decrease was accompanied by a reduction of the proinflammatory cytokines. Increased ALPK1 levels attenuated the testosterone effects in THP1 cells. Finally, we also found that ALPK1 increased the release of TNF-alpha and TGF-beta1 in the human embryonic kidney 293 cells, while testosterone inhibited ALPK1 in the primary kidney cells. Taken together, this data suggests that the balance between ALPK1 and testosterone plays a critical role in the testosterone-mediated inhibition of proinflammatory cytokines.

  12. Increased testosterone to cortisol ratio in psychopathy

    PubMed Central

    Glenn, Andrea L.; Raine, Adrian; Schug, Robert A.; Gao, Yu; Granger, Douglas A.

    2011-01-01

    Only a few studies have examined hormones in psychopathy and results have been mixed. It has been suggested that since hormone systems are highly interconnected, it may be important to examine multiple systems simultaneously to gain a clearer picture of how hormones work together to predispose for a certain construct. In the present study, we attempt to clarify the role of the hormones cortisol and testosterone in psychopathy by examining both hormones in a community sample of 178 adults demonstrating a wide range of psychopathy scores. Results showed that psychopathy scores were associated with an increased ratio of testosterone (baseline) to cortisol responsivity to a stressor. Psychopathy was not associated with either of these measures independently, or with baseline cortisol levels. These findings suggest that these highly interconnected hormone systems may work in concert to predispose to psychopathy. PMID:21133509

  13. Effects of gendered behavior on testosterone in women and men.

    PubMed

    van Anders, Sari M; Steiger, Jeffrey; Goldey, Katherine L

    2015-11-10

    Testosterone is typically understood to contribute to maleness and masculinity, although it also responds to behaviors such as competition. Competition is crucial to evolution and may increase testosterone but also is selectively discouraged for women and encouraged for men via gender norms. We conducted an experiment to test how gender norms might modulate testosterone as mediated by two possible gender→testosterone pathways. Using a novel experimental design, participants (trained actors) performed a specific type of competition (wielding power) in stereotypically masculine vs. feminine ways. We hypothesized in H1 (stereotyped behavior) that wielding power increases testosterone regardless of how it is performed, vs. H2 (stereotyped performance), that wielding power performed in masculine but not feminine ways increases testosterone. We found that wielding power increased testosterone in women compared with a control, regardless of whether it was performed in gender-stereotyped masculine or feminine ways. Results supported H1 over H2: stereotyped behavior but not performance modulated testosterone. These results also supported theory that competition modulates testosterone over masculinity. Our findings thus support a gender→testosterone pathway mediated by competitive behavior. Accordingly, cultural pushes for men to wield power and women to avoid doing so may partially explain, in addition to heritable factors, why testosterone levels tend to be higher in men than in women: A lifetime of gender socialization could contribute to "sex differences" in testosterone. Our experiment opens up new questions of gender→testosterone pathways, highlighting the potential of examining nature/nurture interactions and effects of socialization on human biology.

  14. Effects of gendered behavior on testosterone in women and men

    PubMed Central

    van Anders, Sari M.; Steiger, Jeffrey; Goldey, Katherine L.

    2015-01-01

    Testosterone is typically understood to contribute to maleness and masculinity, although it also responds to behaviors such as competition. Competition is crucial to evolution and may increase testosterone but also is selectively discouraged for women and encouraged for men via gender norms. We conducted an experiment to test how gender norms might modulate testosterone as mediated by two possible gender→testosterone pathways. Using a novel experimental design, participants (trained actors) performed a specific type of competition (wielding power) in stereotypically masculine vs. feminine ways. We hypothesized in H1 (stereotyped behavior) that wielding power increases testosterone regardless of how it is performed, vs. H2 (stereotyped performance), that wielding power performed in masculine but not feminine ways increases testosterone. We found that wielding power increased testosterone in women compared with a control, regardless of whether it was performed in gender-stereotyped masculine or feminine ways. Results supported H1 over H2: stereotyped behavior but not performance modulated testosterone. These results also supported theory that competition modulates testosterone over masculinity. Our findings thus support a gender→testosterone pathway mediated by competitive behavior. Accordingly, cultural pushes for men to wield power and women to avoid doing so may partially explain, in addition to heritable factors, why testosterone levels tend to be higher in men than in women: A lifetime of gender socialization could contribute to “sex differences” in testosterone. Our experiment opens up new questions of gender→testosterone pathways, highlighting the potential of examining nature/nurture interactions and effects of socialization on human biology. PMID:26504229

  15. Testosterone Replacement Therapy: The Emperor's New Clothes.

    PubMed

    Sansone, Andrea; Sansone, Massimiliano; Lenzi, Andrea; Romanelli, Francesco

    2017-02-01

    The mean age of the world population has steadily increased in the last decades, as a result of increased life expectancy and reduced birth rate. Global aging has led to a greater worldwide cost for healthcare: hormonal alterations contribute to the pathogenesis of several conditions and might cause a significant reduction in the perceived sense of well-being. Menopause is archetypal of hormonal alterations occurring during aging: in males, sex hormones do not decrease abruptly, yet testosterone levels decrease steadily and continuously during aging, ultimately resulting in late-onset hypogonadism. Treatment of this condition might mitigate most symptoms; however, testosterone replacement therapy (TRT) should be prescribed only in selected patients and it should not be considered as an antiaging treatment. In recent years, different authors have questioned health risks associated with testosterone treatment; while position statements from many scientific societies seem to be reassuring, the Food and Drug Administration has issued a warning in regard to the possible side effects of this therapy. We aim to review recent controversies and discoveries in regard to TRT.

  16. Transdermal testosterone replacement therapy in men.

    PubMed

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.

  17. Transdermal testosterone replacement therapy in men

    PubMed Central

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  18. Reflexive Testosterone Release: A Model System for Studying the Nongenomic Effects of Testosterone Upon Male Behavior

    PubMed Central

    Nyby, John G.

    2008-01-01

    Male mammals of many species exhibit reflexive testosterone release in mating situations. In house mice (Mus musculus), the dramatic robustness of such release, occurring primarily in response to a novel female, suggests some function. The resulting testosterone elevations typically peak during copulatory behavior and may serve to activate transitory motivational and physiological responses that facilitate reproduction. However, such a function requires that testosterone be working through either nongenomic, or very quick genomic, mechanisms. The first part of the review describes reflexive sex hormone release in house mice. The second part summarizes research implicating testosterone’s fast actions in affecting anxiety, reward, learning, analgesia, and penile reflexes in rodents, all of which could optimize male mating success. The review concludes with a speculative model of how spontaneous and reflexive hormone release might interact to regulate reproductive behavior and why mice appear to be an ideal species for examining testosterone’s quick effects. PMID:17976710

  19. Current approaches to erectile dysfunction and testosterone deficiency.

    PubMed

    Wespes, E

    2010-12-01

    Androgens are essential for the development of the penis and it is well known that testosterone play a critical role in the physiology of erectile function. From animal studies, testosterone insufficiency disrupts cellular-signaling pathways and induces pathologic alterations in penile tissues leading to erectile dysfunction. In human, the testosterone threshold for maintaining erection is low which explains the reason why some contracted men still have an erection due to the androgens produced by the adrenal gland. Testosterone alone can improve erectile function in hypogonadic patients. Associated with PDE5-I, testosterone supplementation is a treatment for the hypogonadic patients non responders to therapy. The article reviews the different aspects of the testosterone role in the pathophysiology of erection.

  20. Testosterone deficiency, insulin-resistant obesity and cognitive function.

    PubMed

    Pintana, Hiranya; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2015-08-01

    Testosterone is an androgenic steroid hormone, which plays an important role in the regulation of male reproduction and behaviors, as well as in the maintenance of insulin sensitivity. Several studies showed that testosterone exerted beneficial effects in brain function, including preventing neuronal cell death, balancing brain oxidative stress and antioxidant activity, improving synaptic plasticity and involving cognitive formation. Although previous studies showed that testosterone deficiency is positively correlated with cognitive impairment and insulin-resistant obesity, several studies demonstrated contradictory findings. Thus, this review comprehensively summarizes the current evidence from in vitro, in vivo and clinical studies of the relationship between testosterone deficiency and insulin-resistant obesity as well as the correlation between either insulin-resistant obesity or testosterone deficiency and cognitive impairment. Controversial reports and the mechanistic insights regarding the roles of testosterone in insulin-resistant obesity and cognitive function are also presented and discussed.

  1. Testosterone, cortisol, and psychopathic traits in men and women.

    PubMed

    Welker, Keith M; Lozoya, Elianna; Campbell, Jocelyn A; Neumann, Craig S; Carré, Justin M

    2014-04-22

    Cortisol and testosterone are theorized to independently and jointly influence antisocial behaviors. The current research examined the independent and interactive effects of baseline testosterone and cortisol on individual differences in psychopathic traits in a relatively large non-clinical sample (N=237). Participants completed the Self-Report Psychopathy - Short Form (SRP; Paulhus, Neumann, & Hare, in press) and provided saliva samples. Analyses indicated that testosterone and cortisol were positively correlated with psychopathic traits in men, but beyond these effects, cortisol moderated the relationship between testosterone and psychopathy in men. The relationship between testosterone and psychopathy within men was positive when cortisol levels were high, but negative when cortisol levels were low. These results have implications for work surrounding the dual hormone hypothesis and suggest that nonclinical variability in psychopathy can be predicted by baseline testosterone and cortisol. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Brain imaging reveals that engagement of descending inhibitory pain pathways in healthy women in a low endogenous estradiol state varies with testosterone.

    PubMed

    Vincent, Katy; Warnaby, Catherine; Stagg, Charlotte J; Moore, Jane; Kennedy, Stephen; Tracey, Irene

    2013-04-01

    The combined oral contraceptive pill (COCP) has been implicated in the development of a number of chronic pain conditions. Modern COCP formulations produce a low endogenous estradiol, low progesterone environment similar to the early follicular phase of the natural menstrual cycle, with a variable effect on serum androgen levels. We used behavioural measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli in healthy women, in both a natural and COCP-induced low endogenous estradiol state, to investigate whether alterations in central pain processing may underlie these observations in COCP users. Although COCP users overall did not require lower temperatures to obtain a fixed pain intensity, alterations in the brain response to these stimuli were observed. In a subgroup of COCP users with significantly reduced serum testosterone, however, lower temperatures were required. Region-of-interest analysis revealed that within key regions of the descending pain inhibitory system, activity in response to noxious stimulation varied with serum testosterone levels in both groups of women. Of particular interest, in COCP users, activity in the rostral ventromedial medulla increased with increasing testosterone and in those women with low testosterone, was significantly reduced compared to controls. These findings suggest that, in a low endogenous estradiol state, testosterone may be a key factor in modulating pain sensitivity via descending pathways. Specifically, failure to engage descending inhibition at the level of the rostral ventromedial medulla may be responsible for the reduction in temperature required by COCP users with low circulating testosterone.

  3. Testosterone biases the amygdala toward social threat approach

    PubMed Central

    Radke, Sina; Volman, Inge; Mehta, Pranjal; van Son, Veerle; Enter, Dorien; Sanfey, Alan; Toni, Ivan; de Bruijn, Ellen R. A.; Roelofs, Karin

    2015-01-01

    Testosterone enhances amygdala reactions to social threat, but it remains unclear whether this neuroendocrine mechanism is relevant for understanding its dominance-enhancing properties; namely, whether testosterone biases the human amygdala toward threat approach. This pharmacological functional magnetic-resonance imaging study shows that testosterone administration increases amygdala responses in healthy women during threat approach and decreases it during threat avoidance. These findings support and extend motivational salience models by offering a neuroendocrine mechanism of motivation-specific amygdala tuning. PMID:26601187

  4. Pharmacokinetics of testosterone cream applied to scrotal skin.

    PubMed

    Iyer, R; Mok, S F; Savkovic, S; Turner, L; Fraser, G; Desai, R; Jayadev, V; Conway, A J; Handelsman, D J

    2017-03-23

    Scrotal skin is thin and has high steroid permeability, but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p < 0.0001) increase in serum testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p < 0.0001), but not dose-dependent, increase in concentration reaching a peak concentration of 1.2 ng/mL (4.1 nm) at 4.9 h which was delayed by 2 h after peak serum testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route.

  5. Testosterone Replacement Therapy on the Natural History of Prostate Disease.

    PubMed

    Moore, Aaron; Butcher, Michael J; Köhler, Tobias S

    2015-08-01

    The physiology of testosterone production and action are closely related to prostatic disease. An understanding of the natural history of testosterone and prostate growth and development is needed in order to understand this complex relationship. Lower urinary tract symptoms (LUTS), benign prostatic hyperplasia (BPH), prostate cancer, and sexual function are common disorders for which testosterone is thought to play a role. Proposed in this review are some theories as to how testosterone interacts to potentially ameliorate these conditions. Further research is needed, but we feel our proposed points are valid given the review of the literature.

  6. The nanochannel delivery system for constant testosterone replacement therapy.

    PubMed

    Ferrati, Silvia; Nicolov, Eugenia; Zabre, Erika; Geninatti, Thomas; Shirkey, Beverly A; Hudson, Lee; Hosali, Sharath; Crawley, Michael; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

    2015-06-01

    The goal of testosterone replacement is to provide long-term physiological supplementation at sufficient levels to mitigate the symptoms of hypogonadism. The objective of this work is to determine if the implantable nanochannel delivery system (nDS) can present an alternative delivery strategy for the long-term sustained and constant release of testosterone. A formulation of common testosterone esters (F1) was developed to enable nanochannel delivery of the low water soluble hormone. In vivo evaluation of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels by liquid chromatography/mass spectrometry and a multiplex assay, respectively, in castrated Sprague-Dawley rats implanted with nDS-F1 implants or polymeric pellets was performed over a 6-month period. The percent of testosterone concentrations observed that fell within the normal range of testosterone levels for each animal was calculated and used to compare the study groups. Sustain release of testosterone in vivo for over 6 months. The subcutaneous release of F1 from nDS implants exhibited sustained in vivo release kinetics and attained stable clinically relevant plasma testosterone levels. Plasma LH and FSH levels were significantly diminished in nDS-F1 implant-treated animals, confirming biological activity of the released testosterone. In conclusion, we demonstrate that nDS-F1 implants represents a novel approach for the treatment of male hypogonadism. Further studies will be performed in view of translating the technology to clinical use. © 2015 International Society for Sexual Medicine.

  7. Mouse Spermatogenesis Requires Classical and Nonclassical Testosterone Signaling.

    PubMed

    Toocheck, Corey; Clister, Terri; Shupe, John; Crum, Chelsea; Ravindranathan, Preethi; Lee, Tae-Kyung; Ahn, Jung-Mo; Raj, Ganesh V; Sukhwani, Meena; Orwig, Kyle E; Walker, William H

    2016-01-01

    Testosterone acts though the androgen receptor in Sertoli cells to support germ cell development (spermatogenesis) and male fertility, but the molecular and cellular mechanisms by which testosterone acts are not well understood. Previously, we found that in addition to acting through androgen receptor to directly regulate gene expression (classical testosterone signaling pathway), testosterone acts through a nonclassical pathway via the androgen receptor to rapidly activate kinases that are known to regulate spermatogenesis. In this study, we provide the first evidence that nonclassical testosterone signaling occurs in vivo as the MAP kinase cascade is rapidly activated in Sertoli cells within the testis by increasing testosterone levels in the rat. We find that either classical or nonclassical signaling regulates testosterone-mediated Rhox5 gene expression in Sertoli cells within testis explants. The selective activation of classical or nonclassical signaling pathways in Sertoli cells within testis explants also resulted in the differential activation of the Zbtb16 and c-Kit genes in adjacent spermatogonia germ cells. Delivery of an inhibitor of either pathway to Sertoli cells of mouse testes disrupted the blood-testis barrier that is essential for spermatogenesis. Furthermore, an inhibitor of nonclassical testosterone signaling blocked meiosis in pubertal mice and caused the loss of meiotic and postmeiotic germ cells in adult mouse testes. An inhibitor of the classical pathway caused the premature release of immature germ cells. Collectively, these observations indicate that classical and nonclassical testosterone signaling regulate overlapping and distinct functions that are required for the maintenance of spermatogenesis and male fertility.

  8. "Mitochondrial Eve", "Y Chromosome Adam", testosterone, and human evolution.

    PubMed

    Howard, James Michael

    2002-01-01

    I suggest primate evolution began as a consequence of increased testosterone in males which increased aggression and sexuality, therefore, reproduction and success. With time, negative effects of excessive testosterone reduced spermatogenesis and started a decline of the group. Approximately 30-40 million years ago, the gene DAZ (Deleted in AZoospermia) appeared on the Y chromosome, increased spermatogenesis, and rescued the early primates from extinction. (Note: DAZ is considered by some to specifically, positively affect spermatogenesis; others suggest it has no effect on spermatogenesis.) Hominid evolution continued with increasing testosterone. The advent of increased testosterone in females of Homo erectus (or Homo ergaster) increased the female-to-male body size ratio, and eventually produced another era of excessive testosterone. Excessive testosterone caused a reduction in population size (bottleneck) that produced the "Mitochondrial Eve" (ME) mechanism. (Only certain females continued during the bottleneck to transmit their mitochondrial DNA.) That is, the ME mechanism culminated, again, in excessive testosterone and reduced spermatogenesis in the hominid line. Approximately 50,000 to 200,000 years ago, a "doubling" of the DAZ gene occurred on the Y chromosome in hominid males which rescued the hominid line with increased spermatogenesis in certain males. This produced the "Y Chromosome Adam" event. The doubling of DAZ allowed further increases in testosterone in hominids that resulted in the increased size and development of the brain. Modern humans periodically fluctuate between the positive and negative consequences of increased levels of testosterone, currently identifiable as the secular trend, increased infections, and reduced spermatogenesis.

  9. Serum testosterone levels in non-dosed females after secondary exposure to 1.62% testosterone gel: effects of clothing barrier on testosterone absorption.

    PubMed

    Stahlman, Jodi; Britto, Margaret; Fitzpatrick, Sherahe; McWhirter, Cecilia; Testino, Samuel A; Brennan, John J; Zumbrunnen, Troy L

    2012-02-01

    To evaluate secondary exposure of testosterone transferred to females from a male partner, dosed with 1.62% testosterone gel after direct skin-to-skin contact with the application site, and to investigate the effect of wearing a t-shirt on testosterone transfer. Across three studies, a total of 72 healthy males applied 5.0 g 1.62% testosterone gel to their abdomen alone, upper arms/shoulders alone, or a combination of their upper arms/shoulders and abdomen (single dose or once daily for 7 days). Male-female contact occurred 2 or 12 hours after testosterone gel application, with males either wearing or not wearing a t-shirt. There were 15 minutes of supervised contact with the application site between the male and his female partner. Blood samples were collected over a 24 hour period in females for assessment of serum testosterone levels at baseline and after contact. Pharmacokinetic parameters included C(max) (maximum serum concentration), AUC(0-24) (area under the serum concentration-time curve from 0-24 hours), and C(av) (time-averaged concentration over the 24-hour period post-contact). Subjects were monitored for adverse events. CLINICAL TRIAL REGISTRATION NCT NUMBERS: Study 1 was not registered (first subject enrolled 8 March 2007); Study 2: 00998933; Study 3, 01130298. Testosterone levels (C(av) and C(max)) in females increased 86-185% from baseline after direct abdominal skin contact, although C(av) levels remained within female eugonadal range. Testosterone concentrations returned to baseline within 48 hours after last skin contact. A t-shirt barrier reduced testosterone transfer by approximately 40-48% when 5.0 g of testosterone gel was applied to the abdomen alone. A t-shirt barrier prevented transfer when 5.0 g of testosterone gel was applied to the upper arms and shoulders or to a combination of the upper arms and shoulders and the abdomen (C(max) and C(av) increased by approximately 5-11%). No major safety events were observed during the studies

  10. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis.

    PubMed

    Cui, Y; Zong, H; Yan, H; Zhang, Y

    2014-06-01

    Testosterone replacement therapy (TRT) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome. Urologists have been concerned about the possibility of TRT causing prostate cancer. The aim of this study was to assess the relationship between TRT and prostate cancer. A literature review was performed to identify all published, randomized controlled trials (RCTs) of testosterone treatment for hypogonadism. The search included the MEDLINE, Embase and the Cochrane Controlled Trials Register databases. Fixed-effect model was chosen for homogeneous studies; otherwise, a random-effect model was used. Inconsistency was quantified by using the I2 statistic, which tests the proportion of heterogeneity across studies. Results of 22 RCTs involving a total of 2351 patients were analyzed. Eleven RCTs were short-term (<12 months) and 11 were long-term (12-36 months) comparisons of TRT with a placebo; TRT was administered transdermally, orally or by injection. Respective odds ratio (OR) and 95% confidence interval (CI) values for injection, transdermal administration and oral administration of short-term TRT were as follows: prostate cancer: 0.39 (0.06-2.45), 1.10 (0.26-4.65) and no oral; biopsy: 5.28 (0.24-113.87), 2.11 (0.32-13.73) and no oral; and prostate nodule: 1.01 (0.13-7.60), no injection and oral. Respective OR and 95% CI values for injection, transdermal administration and oral administration of long-term TRT were as follows: prostate cancer: 2.09 (0.18-24.73), 3.06 (0.12-76.70) and 0.19 (0.01-4.03); biopsy: 2.09 (0.18-24.73), 3.65 (0.88-15.20) and 0.97 (0.13-7.03); and prostate nodule: 3.13 (0.12-80.68), 1.00 (0.06-16.41) and 0.97 (0.13-7.03). Though for some routes of administration and some end points, the OR associated with testosterone administration were >1 indicating increased risk, none of these reached or even approached statistical significance (all P>0.10), which was consistent with the results of subgroup analyses

  11. Effects of human serum on transport of testosterone and estradiol into rat brain.

    PubMed

    Pardridge, W M; Mietus, L J; Frumar, A M; Davidson, B J; Judd, H L

    1980-07-01

    The effect in vivo of the plasma proteins in human serum on the transport of [3H]testosterone (T), [3H]-dihydrotestosterone (DHT), and [3H]estradiol (E2) through the brain capillary wall, i.e., the blood-brain barrier, was studied in anesthetized rats using a tissue-sampling-single-injection technique, In the absence of plasma proteins, approximately 90% of plasma T, DHT, or E2 was transported into brain on a single pass after a bolus carotid injection of labeled hormone. Serum was obtained from 57 patients in seven different clinical conditions: pregnancy, oral contraceptive use, thin and obese postmenopausal, follicular phase female, hirsutism, and normal male; the level (mean +/- SD) of sex hormone-binding globulin (SHBG) varied from 17 +/- 5 nM (hirsutism) to 323 +/- 83 nM (pregnancy). When the carotid injection solution was made 67% serum, the amount of T, DHT, or E2 transported into brain was inhibited in proportion to the concentration of SHBG. Among the patient groups, an overall linear inverse correlation between the mean SHBG level and the mean extraction of unidirectional influx of testosterone (r = 0.99) and estradiol (r = 0.98) was observed. These studies indicate that a) the undirectional clearance by brain of both testosterone and estradiol is inversely related to the SHBG level and b) the fraction of hormone transported into brain greatly exceeds the free (dialyzable) moiety and is essentially equal to the albumin-bound fraction of plasma testosterone or estradiol.

  12. Effects of coconut oil on testosterone-induced prostatic hyperplasia in Sprague-Dawley rats.

    PubMed

    de Lourdes Arruzazabala, María; Molina, Vivian; Más, Rosa; Carbajal, Daisy; Marrero, David; González, Víctor; Rodríguez, Eduardo

    2007-07-01

    Benign prostatic hyperplasia (BPH) is the benign uncontrolled growth of the prostate gland, leading to difficulty with urination. Saw palmetto lipid extracts (SPLE), used to treat BPH, have been shown to inhibit prostate 5a-reductase, and some major components, such as lauric, myristic and oleic acids also inhibit this enzyme. Coconut oil (CO) is also rich in fatty acids, mainly lauric and myristic acids. We investigated whether CO prevents testosterone-induced prostate hyperplasia (PH) in Sprague-Dawley rats. Animals were distributed into seven groups (10 rats each). A negative control group were injected with soya oil; six groups were injected with testosterone (3 mg kg(-1)) to induce PH: a positive control group, and five groups treated orally with SPLE (400 mg kg(-1)), CO or sunflower oil (SO) (400 and 800 mg kg(-1)). Treatments were given for 14 days. Rats were weighed before treatment and weekly thereafter. Rats were then killed and the prostates were removed and weighed. CO (400 and 800 mg kg(-1)), SPLE (400 mg kg(-1)) and SO at 800 mg kg(-1), but not at 400 mg kg(-1), significantly reduced the increase in prostate weight (PW) and PW:body weight (BW) ratio induced by testosterone (% inhibition 61.5%, 82.0%, 43.8% and 28.2%, respectively). Since CO and SPLE, but not SO, contain appreciable concentrations of lauric and myristic acids, these results could be attributed to this fact. In conclusion, this study shows that CO reduced the increase of both PW and PW:BW ratio, markers of testosterone-induced PH in rats.

  13. Tissue engineered testicular prostheses with prolonged testosterone release.

    PubMed

    Raya-Rivera, Atlantida M; Baez, Carlos; Atala, Anthony; Yoo, James J

    2008-08-01

    Bilateral anorchia, either congenital or acquired, often requires testicular prostheses placement and testosterone supplementation. Several types of testosterone compounds and various modes of hormone delivery are currently used clinically, however, their pharmacokinetic properties are not ideal. In this study, we explored the possibility of creating hormone releasing testicular prostheses that could continuously supply and maintain physiologic levels of testosterone in vivo over time. Chondrocytes, harvested from bovine articular cartilage, were seeded on testicular shaped polymer scaffolds at a concentration of 100 x 10(6) ml(-1). The scaffolds were maintained in a bioreactor for 4 weeks to form cartilage tissue. Subsequently, testosterone enanthate (100 microg) was injected into the central hollow space of each testicular prosthesis, and maintained for 40 weeks in culture. A sample of the medium was collected every 2 days for testosterone assays. Another group of ex vivo engineered testicular prostheses was implanted into the scrotal space of castrated athymic mice (n = 10). Intratesticular injection of testosterone enanthate was made into each prosthesis at a concentration of 100 microg. Control groups consisted of animals with castration only (n = 8) and sham operations (n = 5). Testosterone levels were measured prior and 2 weeks after castration, 1 day after testosterone administration, and weekly up to 14 weeks. The engineered testicular prostheses were retrieved at sacrifice for histomorphological and immunocytochemical analyses. Milky white cartilage testicular protheses were formed by 4 weeks. The ex vivo prostheses showed an initial burst effect of testosterone followed by a broad plateau for 16 weeks (>500 ng/dl) and a decreased level of testosterone until 40 weeks. The testosterone levels were physiologic throughout 40 weeks and the entire testosterone released was calculated as 60% of the injected volume. The circulating testosterone levels in the

  14. Free testosterone: clinical utility and important analytical aspects of measurement.

    PubMed

    Shea, Jennifer L; Wong, Pui-Yuen; Chen, Yu

    2014-01-01

    Testosterone, the most abundant androgen in men, is a steroid hormone that is synthesized predominantly by the testes. In women, minor amounts are synthesized in the ovaries. Androgen precursors are also produced and secreted from the adrenal glands in both sexes, where they undergo peripheral conversion to testosterone. Circulating concentrations are approximately 15-25 times higher in adult men compared to women. Maintenance of these levels is necessary for development and maintenance of secondary sexual characteristics, libido, growth, prevention of osteoporosis, and most importantly in men, spermatogenesis. Most testosterone circulates tightly bound to sex hormone-binding globulin (SHBG) or weakly bound to albumin. A minor amount circulates as free testosterone, and it is believed that this is the metabolically active fraction. Measurement of free testosterone is important in the diagnosis of many diseases, most importantly disorders of androgen deficiency in men (i.e., hypogonadism) and androgen excess in women (i.e., polycystic ovary syndrome and hirsutism). Many methodologies are available for free testosterone measurement including the reference methods (equilibrium dialysis and ultrafiltration), analog immunoassay, and calculated free testosterone based on measurement of total testosterone, SHBG, and albumin. Moreover, measurement of bioavailable testosterone, a combination of albumin-bound and free testosterone, also has clinical utility and can be measured by selective protein precipitation or calculation. In this review, the advantages and limitations of each of these methods will be discussed in the context of clinical utility and implementation into a routine hospital laboratory. Furthermore, up and coming methodologies for free testosterone measurement, including liquid chromatography-tandem mass spectrometry, will also be discussed.

  15. Testosterone and social and reproductive behaviour in Aphelocoma jays.

    PubMed

    Vleck; Brown

    1999-11-01

    When there is a direct relationship between testosterone level and payoff in reproductive success through aggression, testosterone levels should be elevated. Elevated testosterone, however, has fitness costs, particularly a decreased tendency to display parental care. Thus the pattern of testosterone secretion in males should vary with the social and mating system. Western scrub-jays, Aphelocoma californica woodhouseii, form monogamous pairs on territories during the breeding season. Mexican jays, A. ultramarina, live in large, stable groups and up to five females within a group attempt nesting each spring. In both species, testosterone levels rose rapidly in March and peak levels did not differ. Elevated testosterone levels were only observed for about 3 weeks in the monogamous western scrub-jay, but were observed into May in Mexican jays, a reflection of prolonged opportunity for males to mate with multiple females and continual interaction with other competing males. In Mexican jays, nonbreeding yearlings had lower testosterone levels than all other age groups. Testosterone in males owning nests did not differ from that in other adult males, many of whom engage in extrapair fertilizations. Testosterone was elevated throughout the incubation phase, but was significantly lower when chicks were present in any nest in the group. Nearly all birds in the group fed all chicks. These observations support the hypothesis that testosterone is elevated when male-male competition is frequent and mating opportunities depend on the outcome of that competition, and testosterone is decreased when the necessity for parental or alloparental care would make its effects deleterious. Copyright 1999 The Association for the Study of Animal Behaviour.

  16. Developmental programing: impact of testosterone on placental differentiation.

    PubMed

    Beckett, E M; Astapova, O; Steckler, T L; Veiga-Lopez, A; Padmanabhan, V

    2014-08-01

    Gestational testosterone treatment causes maternal hyperinsulinemia, intrauterine growth retardation (IUGR), low birth weight, and adult reproductive and metabolic dysfunctions. Sheep models of IUGR demonstrate placental insufficiency as an underlying cause of IUGR. Placental compromise is probably the cause of fetal growth retardation in gestational testosterone-treated sheep. This study tested whether testosterone excess compromises placental differentiation by its androgenic action and/or via altered insulin sensitivity. A comparative approach of studying gestational testosterone (aromatizable androgen) against dihydrotestosterone (non-aromatizable androgen) or testosterone plus androgen antagonist, flutamide, was used to determine whether the effects of testosterone on placental differentiation were programed by its androgenic actions. Co-treatment of testosterone with the insulin sensitizer, rosiglitazone, was used to establish whether the effects of gestational testosterone on placentome differentiation involved compromised insulin sensitivity. Parallel cohorts of pregnant females were maintained for lambing and the birth weight of their offspring was recorded. Placental studies were conducted on days 65, 90, or 140 of gestation. Results indicated that i) gestational testosterone treatment advances placental differentiation, evident as early as day 65 of gestation, and culminates in low birth weight, ii) placental advancement is facilitated at least in part by androgenic actions of testosterone and is not a function of disrupted insulin homeostasis, and iii) placental advancement, while helping to increase placental efficiency, was insufficient to prevent IUGR and low-birth-weight female offspring. Findings from this study may be of relevance to women with polycystic ovary syndrome, whose reproductive and metabolic phenotype is captured by the gestational testosterone-treated offspring.

  17. Androgen replacement therapy: present and future.

    PubMed

    Gooren, Louis J G; Bunck, Mathijs C M

    2004-01-01

    The major goal of androgen substitution is to replace testosterone at levels as close to physiological levels as is possible. For some androgen-dependent functions testosterone is a pro-hormone, peripherally converted to 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2), of which the levels preferably should be within normal physiological ranges. Furthermore, androgens should have a good safety profile without adverse effects on the prostate, serum lipids, liver or respiratory function, and they must be convenient to use and patient-friendly, with a relative independence from medical services. Natural testosterone is viewed as the best androgen for substitution in hypogonadal men. The reason behind the selection is that testosterone can be converted to DHT and E2, thus developing the full spectrum of testosterone activities in long-term substitution. The mainstays of testosterone substitution are parenteral testosterone esters (testosterone enantate and testosterone cipionate) administered every 2-3 weeks. A major disadvantage is the strongly fluctuating levels of plasma testosterone, which are not in the physiological range at least 50% of the time. Also, the generated plasma E2 is usually supraphysiological. A major improvement is parenteral testosterone undecanoate producing normal plasma levels of testosterone for 12 weeks, with normal plasma levels of DHT and E2 also. Subcutaneous testosterone implants provide the patient, depending on the dose of implants, with normal plasma testosterone for 3-6 months. However, their use is not widespread. Oral testosterone undecanoate dissolved in castor oil bypasses the liver via its lymphatic absorption. At a dosage of 80 mg twice daily, plasma testosterone levels are largely in the normal range, but plasma DHT tends to be elevated. For two decades transdermal testosterone preparations have been available and have an attractive pharmacokinetic profile. Scrotal testosterone patches generate supraphysiological

  18. Testosterone replacement in the infertile man

    PubMed Central

    Sabanegh, Edmund

    2016-01-01

    Hypogonadism is a common clinical condition affecting men of different age groups. In addition to its sexual consequences, it has several implications posing significant concerns for a man’s health and well-being. Recent advances in testosterone (T) supplementation have facilitated hypogonadism treatment. Despite that, patients complaining of infertility or seeking conception are still hindered by the unfavorable effects supplemental T has on testicular function. Consequently, alternative approaches that can stimulate endogenous T production are favored. Selective estrogen receptor modulators, gonadotropins and aromatase inhibitors (AIs) can be successful in restoring serum T levels, preserving fertility, and providing symptomatic relief. PMID:28078217

  19. Combined Effects of Eurycoma longifolia and Testosterone on Androgen-Deficient Osteoporosis in a Male Rat Model.

    PubMed

    Saadiah Abdul Razak, Halimatun; Shuid, Ahmad Nazrun; Naina Mohamed, Isa

    2012-01-01

    Androgen-deficient osteoporosis in men is treated with testosterone therapy, which is associated with side effects. Eurycoma longifolia (EL) is known to possess androgenic properties and has been reported to protect bone from androgen-deficient osteoporosis in experimental animal models. The present study aimed to determine the effectiveness of combination therapy of EL and testosterone (T) in treating androgen-deficient osteoporosis. Forty male Sprague-Dawley rats were divided into: sham-operated (SHAM), orchidectomized-control (ORX), orchidectomized with testosterone (ORX + T), orchidectomized with EL (ORX + EL), and orchidectomized with combined T and EL therapy (ORX + T + EL). EL was administered via oral gavages daily at the dose of 15 mg/kg. T was injected intramuscularly at 8 mg/kg and 4 mg/kg for the ORX + T and ORX + T + EL groups, respectively. Following 6 weeks of treatment, the osteocalcin levels of ORX + T and ORX + T + EL groups were significantly lower than the SHAM group (P < 0.05). The posttreatment CTX levels of ORX + T and ORX + T + EL groups were significantly lower than their pretreatment levels (P < 0.05). Biomechanically, the strain parameter of the ORX + T + EL group was significantly higher than the ORX group (P < 0.05). Thus, the combination therapy of EL and low-dose T has potential for treatment of androgen-deficient osteoporosis. The lower T dose is beneficial in reducing the sideeffects of testosterone therapy.

  20. Combined Effects of Eurycoma longifolia and Testosterone on Androgen-Deficient Osteoporosis in a Male Rat Model

    PubMed Central

    Saadiah Abdul Razak, Halimatun; Shuid, Ahmad Nazrun; Naina Mohamed, Isa

    2012-01-01

    Androgen-deficient osteoporosis in men is treated with testosterone therapy, which is associated with side effects. Eurycoma longifolia (EL) is known to possess androgenic properties and has been reported to protect bone from androgen-deficient osteoporosis in experimental animal models. The present study aimed to determine the effectiveness of combination therapy of EL and testosterone (T) in treating androgen-deficient osteoporosis. Forty male Sprague-Dawley rats were divided into: sham-operated (SHAM), orchidectomized-control (ORX), orchidectomized with testosterone (ORX + T), orchidectomized with EL (ORX + EL), and orchidectomized with combined T and EL therapy (ORX + T + EL). EL was administered via oral gavages daily at the dose of 15 mg/kg. T was injected intramuscularly at 8 mg/kg and 4 mg/kg for the ORX + T and ORX + T + EL groups, respectively. Following 6 weeks of treatment, the osteocalcin levels of ORX + T and ORX + T + EL groups were significantly lower than the SHAM group (P < 0.05). The posttreatment CTX levels of ORX + T and ORX + T + EL groups were significantly lower than their pretreatment levels (P < 0.05). Biomechanically, the strain parameter of the ORX + T + EL group was significantly higher than the ORX group (P < 0.05). Thus, the combination therapy of EL and low-dose T has potential for treatment of androgen-deficient osteoporosis. The lower T dose is beneficial in reducing the sideeffects of testosterone therapy. PMID:22924057

  1. The protection of selenium on cadmium-induced inhibition of spermatogenesis via activating testosterone synthesis in mice.

    PubMed

    Ren, Xiang-mei; Wang, Gai-gai; Xu, Dong-qing; Luo, Kang; Liu, Yu-xin; Zhong, Yi-hong; Cai, Yun-qing

    2012-10-01

    Selenium (Se) is an essential trance element in testis. However, the potential protective effects of Se against cadmium (Cd)-induced reproductive toxicity remained to be elucidated. Male ICR mice were orally administered by gavage with Na2SeO3 (0.1, 0.2, 0.4 mg/kg BW) for 1h prior to CdCl2 (5 mg/kg BW) alone or in combination for 15, 25 or 35 days. Cd exposure caused a significant decrease in body weight, sperm concentration and motility as well as plasma testosterone level which was accompanied by decreased antioxidant enzymatic activity of SOD and GSH-Px and by increased lipid peroxidation (as malondialdehyde, MDA). Se pretreatment compensated deficits in the sperm parameters (concentration, motility and morphology) induced by Cd. Se (0.4 mg/kg BW) treatment significantly increased serum testosterone level that was reduced by Cd (on 15th, 25th and 35th day) (P<0.01). Se treatment ameliorated Cd-induced reduction in testicular steroidogenic acute regulatory (StAR) and 17β-hydroxysteroid dehydrogenase (17β-HSD) activities. The present study suggest that the protective potential of Se against Cd-induced reprotoxicity might be due to up-regulation StAR and testosterone synthetic enzyme activity, which could be useful for increasing testosterone synthesis for achieving optimum protection in sperm quality and spermatogenesis.

  2. The long-term efficacy and safety of a testosterone mucoadhesive buccal tablet in testosterone-deficient men.

    PubMed

    Dinsmore, Wallace W; Wyllie, Michael G

    2012-07-01

    What's known on the subject? and What does the study add? Striant® SR is the only available buccal delivery system for testosterone replacement therapy. Previous pharmacokinetic studies have shown that Striant SR effectively produces physiological serum testosterone levels in hypogonadal men. Efficacy and safety data from previously unpublished studies over 2 years of continuous use indicate that Striant SR is effective long term in maintaining serum testosterone within a physiological range, is well tolerated and has a high level of patient acceptance. Striant® sustained-release (SR) is a mucoadhesive buccal tablet (30 mg testosterone, The Urology Company) that adheres to the gum surface in the mouth providing controlled- and sustained-release of testosterone over a 12-h dosing period, offering a unique and rational method of testosterone delivery. Striant SR is indicated for testosterone-replacement therapy (TRT) for male hypogonadism when testosterone deficiency has been confirmed by clinical features and biochemical tests. Pharmacokinetic studies have shown that testosterone is released from Striant SR in a manner similar to the normal daily rhythm of endogenous testosterone secretion, with serum levels rising rapidly after insertion and peak levels reached by the second 12-hourly dose with no accumulation over time. In clinical trials involving hypogonadal men receiving Striant SR for up to 2 years, mean serum testosterone levels have always remained within the normal range. Striant SR is well tolerated, with gum-related disorders (such as irritation, inflammation and gingivitis) and taste perversion being the most commonly reported adverse events, reported by 5.6-16.3% and 3.0-4.1% of patients, respectively. Once patients have become accustomed to it, Striant SR has a high level of patient acceptance. In a long-term study, 90% of patients rated the twice-daily dosing as acceptable, just under half preferred it to other forms of TRT that they have used and

  3. Testosterone in men with hypogonadism and high cardiovascular risk, Pros.

    PubMed

    Rosano, Giuseppe M C; Vitale, Cristiana; Fini, Massimo

    2015-11-01

    Although numerous randomized studies have shown that testosterone replacement therapy (TRT) improves intermediate outcomes in patients at risk and in those with proven cardiovascular disease (CVD), results derived mainly from registries and observational studies have suggested an increased cardiovascular risk in elderly men receiving often supra-therapeutic doses of testosterone. Recent meta-analyses have shown that when testosterone has been used in patients with pre-existing cardiovascular conditions, the effect on the disease has been either beneficial or neutral. Similar results have been reported in hypo- and eugonadal men. Contrasting results have been reported by two trials of testosterone treatment in frail elderly men. Reports from poorly analyzed databases have reported an increased risk of cardiovascular events with testosterone use. More recently, a population-based study showed no increased cardiovascular risk of testosterone replacement in hypogonadal men. Available data from controlled clinical trials suggest that the use of testosterone in elderly men does not increase cardiovascular risk nor the risk of events. Studies in men with CVD, angina, or heart failure report a benefit from testosterone replacement in men with or without hypogonadism. Therefore, at present, the cardiovascular benefits of TRT in elderly men outweigh the risks. This is particularly evident in those men with pre-existing CVD.

  4. A Mendelian randomization study of testosterone and cognition in men

    PubMed Central

    Zhao, Jie V.; Lam, Tai Hing; Jiang, Chaoqiang; Cherny, Stacey S.; Liu, Bin; Cheng, Kar Keung; Zhang, Weisen; Leung, Gabriel M.; Schooling, C Mary

    2016-01-01

    Testosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (−0.02 per nmol/L testosterone, 95% confidence interval (CI) −0.06–0.02) or MMSE score (0.06, 95% CI −0.002–0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men. PMID:26864717

  5. Methadone induces testosterone suppression in patients with opioid addiction

    PubMed Central

    Bawor, Monica; Dennis, Brittany B.; Samaan, M. Constantine; Plater, Carolyn; Worster, Andrew; Varenbut, Michael; Daiter, Jeff; Marsh, David C.; Desai, Dipika; Steiner, Meir; Anglin, Rebecca; Coote, Margaret; Pare, Guillaume; Thabane, Lehana; Samaan, Zainab

    2014-01-01

    Sex hormones may have a role in the pathophysiology of substance use disorders, as demonstrated by the association between testosterone and addictive behaviour in opioid dependence. Although opioid use has been found to suppress testosterone levels in men and women, the extent of this effect and how it relates to methadone treatment for opioid dependence is unclear. The present multi-centre cross-sectional study consecutively recruited 231 patients with opioid dependence from methadone clinics across Ontario, Canada between June and December of 2011. We obtained demographic details, substance use, psychiatric history, and blood and urine samples from enrolled subjects. The control group included 783 non-opioid using adults recruited from a primary care setting in Ontario, Canada. Average testosterone level in men receiving methadone treatment was significantly lower than controls. No effect of opioids including methadone on testosterone level in women was found and testosterone did not fluctuate significantly between menstrual cycle phases. In methadone patients, testosterone level was significantly associated with methadone dose in men only. We recommend that testosterone levels be checked in men prior and during methadone and other opioid therapy, in order to detect and treat testosterone deficiency associated with opioids and lead to successful methadone treatment outcomes. PMID:25155550

  6. Roles of Testosterone Replacement in Cardiac Ischemia-Reperfusion Injury.

    PubMed

    Pongkan, Wanpitak; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-01-01

    Testosterone is an anabolic steroid hormone, which is the major circulating androgen hormone in males. Testosterone levels decreasing below the normal physiological levels lead to a status known as androgen deficiency. Androgen deficiency has been shown to be a major risk factor in the development of several disorders, including obesity, metabolic syndrome, and ischemic heart disease. In the past decades, although several studies from animal models as well as clinical studies demonstrated that testosterone exerted cardioprotection, particularly during ischemia-reperfusion (I/R) injury, other preclinical and clinical studies have shown an inverse relationship between testosterone levels and cardioprotective effects. As a result, the effects of testosterone replacement on the heart remain controversial. In this review, reports regarding the roles of testosterone replacement in the heart following I/R injury are comprehensively summarized and discussed. At present, it may be concluded that chronic testosterone replacement at a physiological dose demonstrated cardioprotective effects, whereas acute testosterone replacement can cause adverse effects in the I/R heart. © The Author(s) 2015.

  7. Functional significance of men's testosterone reactivity to social stimuli.

    PubMed

    Zilioli, Samuele; Bird, Brian M

    2017-10-01

    Rapid testosterone fluctuations in response to social stimuli are observed across a wide range of species, and the highly conserved nature of these fluctuations suggests an adaptive function. This paper reviews the current literature on testosterone reactivity, primarily in human males, and illustrates how life-history theory provides an adequate theoretical framework to interpret findings. The review is structured around supporting evidence suggesting that situations implicated in mating effort either directly (e.g., interactions with a mate) or indirectly (e.g., intrasexual competition) are generally associated with a brief elevation of testosterone, while situations implicated in parenting effort (e.g., nurturant interactions with offspring) are generally associated with a decline in testosterone. Further, we discuss how these fluctuations in testosterone have been linked to future behaviors, and how situational, motivational, and physiological variables moderate the interplay between social stimuli, testosterone reactivity, and behavior. Supporting the notion that testosterone can play a causal role in modulating behavior in response to social stimuli, we also summarize recent single administration studies examining the effects of testosterone on physiology, neurobiology, and behavior. A conceptual model provides links between supported findings, and hypothesized pathways requiring future testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. An improved ultrafiltration method for determining free testosterone in serum

    SciTech Connect

    Vlahos, I.; MacMahon, W.; Sgoutas, D.; Bowers, W.; Thompson, J.; Trawick, W.

    1982-11-01

    In this method, we use the Amicon MPS-1 centrifugal ultrafiltration device and the YMB membrane in measuring free testosterone in serum. Two independent assays are combined: total testosterone and the ultrafiltrable fraction of added (/sup 3/H)testosterone. The unbound fraction is determined in 0.15-0.5 mL ultrafiltrates of 0.6 to 1 mL of variably diluted serum that has been equilibrated with (/sup 3/H)testosterone at 37 degrees C. The assay is rapid (less than 1 h), practicable (requires 0.6 mL of serum), and reproducible (CV 3.2% within assay, 3.9% between assays). Accuracy was evaluated as the fraction of free testosterone in the ultrafiltrate of dialyzed serum vs that in a prior dialysate; they were the same confirming the validity of the free testosterone measurement. Samples from ostensibly healthy men and women and from hirsute and pregnant women gave results that agreed with those obtained by equilibrium dialysis. Total testosterone concentrations for normal and hirsute women showed considerable overlap, but data on free testosterone concentrations in these populations were better resolved.

  9. Fetal Testosterone, Socio-Emotional Engagement and Language Development

    ERIC Educational Resources Information Center

    Farrant, Brad M.; Mattes, Eugen; Keelan, Jeff A.; Hickey, Martha; Whitehouse, Andrew J. O.

    2013-01-01

    The present study investigated the relations among fetal testosterone, child socio-emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly…

  10. Does testosterone affect foraging behavior in male frogs?

    PubMed

    Desprat, Julia L; Mondy, Nathalie; Lengagne, Thierry

    2017-02-19

    During the breeding season, males often produce costly and extravagant displays or physical ornaments to attract females. Numerous studies have established that testosterone could directly influence the expression of certain sexual signals. However, few of these studies have focused on the indirect role that testosterone could play in modulating prey detection and visual performance to improve the foraging ability of males and hence their acquisition of nutritional resource. In the present study, we experimentally modified the testosterone levels of European tree frog males (Hyla arborea), staying in the natural range previously measured in the field, and we investigated the effect of testosterone on the foraging ability of individuals. Foraging capacities were measured on males placed in an arena with a virtual cricket moving on a computer screen. Our results demonstrated a significant effect of testosterone on the hunting behavior of H. arborea. We observed that testosterone reduced the orientation latency to virtual prey for supplemented males compared to controls. In addition, testosterone significantly increased the attack promptness of male frogs. Finally, our experiment did not demonstrate any impact of testosterone on male attack success.

  11. Postnatal testosterone levels and temperament in early infancy.

    PubMed

    Alexander, Gerianne M; Saenz, Janet

    2011-12-01

    Recent research showing associations between behavior and postnatal testosterone levels in male infants has suggested that the transient activation of the hypothalamic-pituitary-gonadal axis in early infancy may influence the expression of gender phenotypes in later development (i.e., the postnatal hormone hypothesis). As a further test of the relationship between postnatal hormones and behavior in infancy, we measured digit ratios and salivary testosterone in 76 male and female infants (3-4 months of age) and parents completed the Infant Behavior Questionnaire-Revised, a well-established measure of temperament in the first year of life. Consistent with our earlier findings, there were no significant sex differences in salivary testosterone levels and testosterone levels were unrelated to measures of behavior in female infants. However, in male infants, higher androgen levels predicted greater Negative Affectivity. Further examination of the four scales contributing to the measure of Negative Affectivity showed testosterone levels were a significant predictor of scores on the Distress to Limitations scale, but not of scores on Fear, Sadness, or Reactivity scales. This sex-specific association between salivary testosterone and behavior in infants is consistent with animal research showing higher prenatal androgens associated with typical male development lower the threshold of sensitivity to endogenous testosterone in postnatal life. In sum, these data provide additional support for the postnatal hormone hypothesis and suggest postnatal testosterone levels may influence the development of emotional regulation in male infants.

  12. Testosterone Regulates Tight Junction Proteins and Influences Prostatic Autoimmune Responses

    PubMed Central

    Meng, Jing; Mostaghel, Elahe A.; Vakar-Lopez, Funda; Montgomery, Bruce; True, Larry; Nelson, Peter S.

    2015-01-01

    Testosterone and inflammation have been linked to the development of common age-associated diseases affecting the prostate gland including prostate cancer, prostatitis, and benign prostatic hypertrophy. We hypothesized that testosterone regulates components of prostate tight junctions which serve as a barrier to inflammation, thus providing a connection between age- and treatment-associated testosterone declines and prostatic pathology. We examined the expression and distribution of tight junction proteins in prostate biospecimens from mouse models and a clinical study of chemical castration, using transcript profiling, immunohistochemistry and electron microscopy. We determined that low serum testosterone is associated with reduced transcript and protein levels of Claudin 4 and Claudin 8, resulting in defective tight junction ultrastructure in benign prostate glands. Expression of Claudin 4 and Claudin 8 was negatively correlated with the mononuclear inflammatory infiltrate caused by testosterone deprivation. Testosterone suppression also induced an auto-immune humoral response directed toward prostatic proteins. Testosterone supplementation in castrate mice resulted in re-expression of tight junction components in prostate epithelium and significantly reduced prostate inflammatory cell numbers. These data demonstrate that tight junction architecture in the prostate is related to changes in serum testosterone levels, and identify an androgen-regulated mechanism that potentially contributes to the development of prostate inflammation and consequent pathology. PMID:21761342

  13. Testosterone modulates spatial recognition memory in male rats.

    PubMed

    Hawley, Wayne R; Grissom, Elin M; Martin, Ryan C; Halmos, Miklos B; Bart, Corrine L S; Dohanich, Gary P

    2013-04-01

    A growing body of research indicates that testosterone influences spatial cognition in male rats; however, the overwhelming majority of studies have been conducted on tasks motivated by either food deprivation or water escape. The hippocampus-dependent version of the Y-maze task, which characterizes spatial recognition memory, capitalizes on the propensity of rats to gravitate toward novel spatial environments and is not contingent upon either appetite or the stress associated with water escape, two factors also affected by testosterone. Accordingly, the aim of the current study was to examine the effects of orchidectomy and subsequent testosterone treatment on spatial recognition memory. Orchidectomy did not impact spatial recognition memory when the delay between the information and retention trials of the Y-maze task was 24h. Alternatively, on the second Y-maze task, which featured a 48-h delay between trials, orchidectomy reduced, and treatments that produced higher levels of testosterone restored, preference for the arm associated with the novel spatial environment. Importantly, there were no differences in activity levels as a function of orchidectomy or testosterone treatment on either of the two tasks. Consistent with previous findings, orchidectomy attenuated, and testosterone treatment restored, both body weight gain and the relative weight of the androgen-sensitive ischiocavernosus muscle, which confirmed the efficacy of orchidectomy and testosterone treatments on physiological outcomes. Therefore, testosterone influenced spatial cognition on a task that minimized the influence of non-mnemonic factors and took advantage of the innate preference of rodents to seek out novel spatial environments.

  14. Single-Dose Testosterone Administration Impairs Cognitive Reflection in Men.

    PubMed

    Nave, Gideon; Nadler, Amos; Zava, David; Camerer, Colin

    2017-10-01

    In nonhumans, the sex steroid testosterone regulates reproductive behaviors such as fighting between males and mating. In humans, correlational studies have linked testosterone with aggression and disorders associated with poor impulse control, but the neuropsychological processes at work are poorly understood. Building on a dual-process framework, we propose a mechanism underlying testosterone's behavioral effects in humans: reduction in cognitive reflection. In the largest study of behavioral effects of testosterone administration to date, 243 men received either testosterone or placebo and took the Cognitive Reflection Test (CRT), which estimates the capacity to override incorrect intuitive judgments with deliberate correct responses. Testosterone administration reduced CRT scores. The effect remained after we controlled for age, mood, math skills, whether participants believed they had received the placebo or testosterone, and the effects of 14 additional hormones, and it held for each of the CRT questions in isolation. Our findings suggest a mechanism underlying testosterone's diverse effects on humans' judgments and decision making and provide novel, clear, and testable predictions.

  15. Lowered testosterone in male obesity: mechanisms, morbidity and management

    PubMed Central

    Fui, Mark Ng Tang; Dupuis, Philippe; Grossmann, Mathis

    2014-01-01

    With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials. PMID:24407187

  16. Testosterone stimulates reproductive behavior during autumn in mockingbirds (Mimus polyglottos).

    PubMed

    Logan, C A; Carlin, C A

    1991-06-01

    Mockingbirds normally secrete little or no testosterone during the period of autumnal territoriality. To determine the behavioral effects of exogenously administered testosterone, 20-mm lengths of Silastic tubing filled with crystalline testosterone were implanted into free-living resident mockingbirds during the autumn. Control residents were given sealed empty implants. Focal animal sampling showed that T-implanted males sang significantly more than controls. Perhaps as a consequence, a significantly greater percentage of the T-implanted males acquired mates. Though nest building does not naturally occur in autumn, T-implanted males also showed significantly more nest building than control males. However, T-implanted males only built if there was a female in the territory, suggesting a synergy between the presence of testosterone and social cues provided by the female. Examination of the effects of testosterone on territorial aggression showed that despite the high levels of territorial activity common in this species in autumn, territorial fights were unaffected by the presence of testosterone. One aggressive call, known to function in fall territorial defense, was significantly decreased in T-implanted versus control males. The presence of fall testosterone appears to stimulate a number of reproductive activities in mockingbirds, leaving autumnal aggressive interactions either unchanged or decreased. We discuss the application of these data to the effects of testosterone on the mockingbird's reproductive behavior during the breeding season.

  17. Testosterone release and social context: when it occurs and why.

    PubMed

    Gleason, Erin D; Fuxjager, Matthew J; Oyegbile, Temitayo O; Marler, Catherine A

    2009-10-01

    The functions of rapid increases in testosterone seem paradoxical because they can occur in response to different social contexts, such as male-male aggressive encounters and male-female sexual encounters. This suggests that context may impact the functional consequences of changes in testosterone, whether transient or long term. Many studies, including those with California mice (Peromyscus californicus), have addressed these issues using manipulations and species comparisons, but many areas remain to be investigated. We report a study here that suggests transient increases in testosterone after social competition influence future competitive behavior, but social experience alone may also be critical in determining future behavior. In other rodents, a comparable testosterone surge occurs in response to sexual stimulation, but the function is not entirely understood. In addition to competitive and sexual behavior, testosterone impacts other systems instrumental to social behaviors, including paternal behavior and degree of monogamy. Thus, mechanisms regulated by testosterone, such as the vasopressin and aromatase systems, may also be influenced by rapid surges of testosterone in aggressive or sexual contexts. We discuss how the functions of testosterone may overlap in some contexts.

  18. Fetal Testosterone, Socio-Emotional Engagement and Language Development

    ERIC Educational Resources Information Center

    Farrant, Brad M.; Mattes, Eugen; Keelan, Jeff A.; Hickey, Martha; Whitehouse, Andrew J. O.

    2013-01-01

    The present study investigated the relations among fetal testosterone, child socio-emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly…

  19. Oral Cancer

    MedlinePlus

    Oral Cancer Basic description Cancer can affect any part of the oral cavity, including the lips, tongue, mouth, and throat. There are 2 kinds of oral cancer: oral cavity cancer and oropharyngeal cancer. The most ...

  20. Testosterone deficiency in the aging male

    PubMed Central

    McBride, J. Abram; Carson, Culley C.; Coward, Robert M.

    2016-01-01

    Treatment for hypogonadism is on the rise, particularly in the aging population. Yet treatment in this population represents a unique challenge to clinicians. The physiology of normal aging is complex and often shares the same, often vague, symptoms of hypogonadism. In older men, a highly prevalent burden of comorbid medical conditions and polypharmacy complicates the differentiation of signs and symptoms of hypogonadism from those of normal aging, yet this differentiation is essential to the diagnosis of hypogonadism. Even in older patients with unequivocally symptomatic hypogonadism, the clinician must navigate the potential benefits and risks of treatment that are not clearly defined in older men. More recently, a greater awareness of the potential risks associated with treatment in older men, particularly in regard to cardiovascular risk and mortality, have been appreciated with recent changes in the US Food and Drug Administration recommendations for use of testosterone in aging men. The aim of this review is to provide a framework for the clinician evaluating testosterone deficiency in older men in order to identify correctly and treat clinically significant hypogonadism in this unique population while minimizing treatment-associated harm. PMID:26834840

  1. Testosterone therapy improves erectile function and libido in hypogonadal men.

    PubMed

    Rizk, Paul J; Kohn, Taylor P; Pastuszak, Alexander W; Khera, Mohit

    2017-11-01

    Erectile dysfunction and decreased libido are common complaints in the older male population. Recent studies have elucidated the role testosterone therapy (TTh) can play in men with low testosterone levels. The aim of this review is to provide an overview of these findings and the utility of TTh. We specifically examine the role of TTh on erectile function, coadministration with phosphodiesterase type 5 inhibitors, and libido. Recent publications suggest that TTh improves mild erectile dysfunction, though may be less useful in men with more severe erectile dysfunction. In men unresponsive to phosphodiesterase type 5 inhibitors and with mild erectile dysfunction, TTh can further improve erectile function. TTh has also shown consistent benefit in improving libido in men with low testosterone levels at baseline, with no additional improvements once testosterone levels are normalized. The available literature supports a role for TTh in men with low testosterone levels, erectile dysfunction, and low libido, with symptomatic improvement in these men.

  2. Understanding testosterone variation in a tropical lek-breeding bird.

    PubMed

    Ryder, Thomas B; Horton, Brent M; Moore, Ignacio T

    2011-08-23

    Male reproductive coalitions, in which males cooperate to attract females, are a rare strategy among vertebrates. While some studies have investigated ultimate aspects of these relationships, little is known about the mechanistic role that hormones play in modulating cooperative behaviours. Here, we examined male testosterone variation in a tropical lekking bird, the wire-tailed manakin (Pipra filicauda), which exhibits cooperative male-male display coalitions. We found that testosterone levels in territorial males were comparable to those of temperate breeding birds, a surprising result given their environmental, social and reproductive dynamics. In addition, social status rather than plumage was a strong predictor of testosterone variation. Territorial males had significantly higher testosterone levels than did two other plumage classes of floater males, who do not hold territories. We hypothesize that testosterone variation plays an important role in the establishment of male dominance hierarchies (competition), while concurrently facilitating stable display partnerships (cooperation).

  3. Testosterone, estradiol, ACTH and musical, spatial and verbal performance.

    PubMed

    Hassler, M; Gupta, D; Wollmann, H

    1992-01-01

    Testosterone, estradiol, and ACTH were determined in blood serum of 26 healthy males aged 19.16 and of 25 healthy females aged 18.77 years on average, and results were correlated with test scores of three spatial tests, a verbal fluency measure, and a test measuring general musical ability. In addition, hemispheric lateralization for verbal material and handedness was assessed. While testosterone and estradiol alone were not significantly related to any of the cognitive or musical tests, testosterone/estradiol ratio was significantly negatively correlated with spatial tests, and ACTH was significantly positively correlated with spatial and musical tests. Correlations were stronger in females than in males. The laterality index was significantly negatively correlated with testosterone in males indicating that right hemisphere involvement in verbal processing was associated with high testosterone levels.

  4. Pubertal testosterone predicts mental rotation performance of young adult males.

    PubMed

    Vuoksimaa, Eero; Kaprio, Jaakko; Eriksson, C J Peter; Rose, Richard J

    2012-11-01

    Robust sex differences in some spatial abilities that favor males have raised the question of whether testosterone contributes to those differences. There is some evidence for prenatal organizational effects of testosterone on male-favoring spatial abilities, but not much is known about the role of pubertal testosterone levels on adult cognitive abilities. We studied the association between pubertal testosterone (at age 14) and cognitive performance in young adulthood (at age 21-23), assessing male-favoring, female-favoring, and sex-neutral cognitive domains in a population-based sample of 130 male and 178 female twins. Pubertal testosterone was negatively associated with performance in the Mental Rotation Test in young adult men (r=-.27), while among women no significant associations between testosterone and cognitive measures were detected. The significant association among men remained after controlling for pubertal development. Confirmatory within-family comparisons with one-sided significance testing yielded a negative correlation between twin pair differences in testosterone levels and Mental Rotation Test performances in 35 male twin pairs (r=-.32): the twin brother with higher testosterone performed less well on the Mental Rotation Test. That association was evident in 18 pairs of dizygotic male twin pairs (r=-.42; analysis controlling for shared environmental effects). In contrast, the association of differences was not evident among 17 monozygotic male twin pairs (r=-.07; analysis controlling for shared genetic influences). Results suggest that pubertal testosterone levels are related specifically to male-favoring spatial ability and only among men. Within-family analyses implicated possible shared genetic effects between pubertal testosterone and mental rotation ability.

  5. Testosterone Therapy Can Interact With Thrombophilia, Leading to Osteonecrosis.

    PubMed

    Glueck, Charles J; Riaz, Rashid; Prince, Marloe; Freiberg, Richard A; Wang, Ping

    2015-12-01

    Although this effect is not widely recognized, testosterone therapy can interact with thrombophilia, causing osteonecrosis. In 12 men and 4 women who had idiopathic osteonecrosis a median of 6 months after the onset of testosterone therapy, the authors examined the interaction between testosterone therapy and previously undiagnosed thrombophilia. The authors hypothesized that patients who had osteonecrosis after starting testosterone therapy were more likely than 110 normal control subjects or 48 patients who had osteonecrosis and were not receiving testosterone therapy to have thrombophilia. Measures of thrombophilia included Factor V Leiden, prothrombin, PAI-1 gene mutations, Factor VIII, Factor XI, anticardiolipin antibody immunoglobulin G or immunoglobulin M, and homocysteine values. In 10 cases, osteonecrosis occurred 6 months or less after the onset of testosterone therapy, and in all 16 cases, it occurred after a median of 6 months of testosterone therapy. Of the 16 cases, 5 (31%) were Factor V Leiden heterozygotes vs 2 of 109 (2%) healthy control subjects (P=.0003) and 4 of 48 patients who had osteonecrosis and were not receiving testosterone therapy (P=.04). Of the 16 cases, 4 (25%) had high (>150%) Factor VIII levels vs 7 of 103 (7%) healthy control subjects (P=.04), and 3 (19%) had high (>150%) Factor XI levels vs 3 of 101 (3%) healthy control subjects (P=.03). Of the 16 patients with osteonecrosis, 14 (88%) had at least 1 abnormal procoagulant value (of the 8 measured) vs 47 of 110 (43%) healthy control subjects (P=.0009). Of the 5 men whose serum estradiol level was measured while they were receiving testosterone therapy, this level was high (≥42.6 pg/mL) in 4. When testosterone therapy is given to patients with thrombophilia, they are at increased risk for osteonecrosis.

  6. Testosterone Concentrations in Diabetic and Nondiabetic Obese Men

    PubMed Central

    Dhindsa, Sandeep; Miller, Michael G.; McWhirter, Cecilia L.; Mager, Donald E.; Ghanim, Husam; Chaudhuri, Ajay; Dandona, Paresh

    2010-01-01

    OBJECTIVE To determine the prevalence of subnormal testosterone concentrations in patients with obesity and with type 2 diabetes in a primary care clinic population. RESEARCH DESIGN AND METHODS Free testosterone concentrations of 1,849 men (1,451 nondiabetic and 398 diabetic) in the Hypogonadism In Males (HIM) study were analyzed. The HIM study was a U.S.-based cross-sectional study designed to define the prevalence of hypogonadism in men aged >45 years. Free testosterone was measured by equilibrium dialysis. RESULTS The prevalence of subnormal free testosterone concentrations in lean, overweight, and obese nondiabetic men was 26% (n = 275), 29% (n = 687), and 40% (n = 489), respectively (P < 0.001 for trend), and 44% (n = 36), 44% (n = 135), and 50% (n = 227), respectively, in diabetic men (P = 0.46 for trend within group and P < 0.05 compared with nondiabetic men). The mean free testosterone concentration of diabetic men was significantly lower than that of nondiabetic men. Free testosterone concentrations were negatively and significantly (P < 0.001) related to age (r = −0.37), BMI (r = −0.18), and sex hormone–binding globulin (r = −0.11) in multiple regression analysis. The average decline of free testosterone concentrations was 7.8 pg/ml per decade in nondiabetic men and 8.4 pg/ml per decade in diabetic men. CONCLUSIONS Forty percent of obese nondiabetic men and 50% of obese diabetic men aged ≥45 years have subnormal free testosterone concentrations. In view of its high prevalence, obesity is probably the condition most frequently associated with subnormal free testosterone concentrations in males. The concomitant presence of diabetes is associated with an additional increase in the prevalence of subnormal free testosterone concentrations. PMID:20200299

  7. Pubertal Testosterone Predicts Mental Rotation Performance of Young Adult Males

    PubMed Central

    Vuoksimaa, Eero; Kaprio, Jaakko; Eriksson, C. J. Peter; Rose, Richard J.

    2012-01-01

    Summary Robust sex differences in some spatial abilities that favor males have raised the question of whether testosterone contributes to those differences. There is some evidence for prenatal organizational effects of testosterone on male-favoring spatial abilities, but not much is known about the role of pubertal testosterone levels on adult cognitive abilities. We studied the association between pubertal testosterone (at age 14) and cognitive performance in young adulthood (at age 21–23), assessing male-favoring, female-favoring, and sex-neutral cognitive domains in a population-based sample of 130 male and 178 female twins. Pubertal testosterone was negatively associated with performance in the Mental Rotation Test in young adult men (r = −.27), while among women no significant associations between testosterone and cognitive measures were detected. The significant association among men remained after controlling for pubertal development. Confirmatory within-family comparisons with one-sided significance testing yielded a negative correlation between twin pair differences in testosterone levels and Mental Rotation Test performances in 35 male twin pairs (r = −.32):the twin brother with higher testosterone performed less well on the Mental Rotation Test. That association was evident in18 pairs of dizygotic male twin pairs (r = −.42; analysis controlling for shared environmental effects). In contrast, the association of differences was not evident among 17 monozygotic male twin pairs (r = −.07; analysis controlling for shared genetic influences). Results suggest that pubertal testosterone levels are related specifically to male-favoring spatial ability and only among men. Within-family analyses implicated possible shared genetic effects between pubertal testosterone and mental rotation ability. PMID:22520299

  8. Testosterone deficiency in dialysis patients: Difference between dialysis techniques.

    PubMed

    Cigarrán, Secundino; Coronel, Francisco; Florit, Enrique; Calviño, Jesús; Villa, Juan; Gonzalez Tabares, Lourdes; Herrero, José Antonio; Carrero, Juan Jesús

    Testosterone deficiency is a prevalent condition in male patients with chronic kidney disease. However, it is not known whether the type of renal replacement therapy has an impact on testosterone deficiency that accompanies loss of renal function. The cross-sectional study enrolled 79 prevalent male patients on dialysis; 43 on haemodialysis (HD) and 36 on peritoneal dialysis (PD). The median age was 69 years and 31.6% were diabetics. Endogenous testosterone levels were measured by immunoluminescence assay (normal range 3-10.5ng/ml), while nutritional/inflammatory markers, bone and mineral metabolism markers, anaemia, type of dialysis technique and time on dialysis were also assessed. Body composition was evaluated by bioimpedance vector analysis and bioimpedance spectroscopy. Testosterone deficiency was defined as levels below 3ng/ml. Mean testosterone levels were 8.81±6.61ng/ml. Testosterone deficiency affected 39.5% of HD patients and only 5.6% of PD patients. In the univariate analysis, testosterone levels were directly correlated with type of dialysis technique (HD) (Rho Spearman 0.366; P<.001) and time on dialysis (Rho -0.412; P=.036) and only with the HD technique in the multivariate analysis. No other significant correlations were found. Circulating testosterone levels in men on dialysis were independently associated with HD technique. It can be concluded that a new factor -namely the dialysis technique- may be associated with falling testosterone levels and the associated loss of muscle mass and inflammation. Further studies are needed to establish whether the dialysis technique itself triggers testosterone elimination. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy

    PubMed Central

    Baillargeon, Jacques; Urban, Randall J.; Kuo, Yong-Fang; Ottenbacher, Kenneth J.; Raji, Mukaila A.; Du, Fei; Lin, Yu-li; Goodwin, James S.

    2014-01-01

    Background Testosterone therapy for older men has increased substantially over the past decade. Research on the effects of testosterone therapy on cardiovascular outcomes has yielded inconsistent results. Objective To examine the risk of myocardial infarction (MI) in a population-based cohort of older men receiving intramuscular testosterone. Method Using a 5% national sample of Medicare beneficiaries, we identified 6355 patients treated with at least 1 injection of testosterone between January 1, 1997, and December 31, 2005. We matched this cohort to 19 065 testosterone nonusers at a 1:3 ratio based on a composite MI prognostic score. Patients were followed until December 31, 2005, or until they lost coverage from Medicare, enrolled in a health maintenance organization, experienced a MI, or died. Result In a Cox regression analysis adjusting for demographic and clinical characteristics, receipt of testosterone therapy was not associated with an increased risk of MI (hazard ratio [HR] = 0.84; 95% CI = 0.69–1.02). In this analysis, there was an interaction between receipt of testosterone and quartile of risk of MI (P = 0.023). For men in the highest quartile of the MI prognostic score, testosterone therapy was associated with a reduced risk of MI (HR = 0.69; 95% CI = 0.53–0.92), whereas there was no difference in risk for the first (HR = 1.20; 95% CI = 0.88–1.67), second (HR = 0.94; 95% CI = 0.69–1.30), and third quartiles (HR = 0.78; 95% CI = 0.59–1.01). Conclusion Older men who were treated with intramuscular testosterone did not appear to have an increased risk of MI. For men with high MI risk, testosterone use was modestly protective against MI. PMID:24989174

  10. Contemporary perspective and management of testosterone deficiency: Modifiable factors and variable management.

    PubMed

    Hisasue, Shin-ichi

    2015-12-01

    Testosterone deficiency can occur in males of all ages. In adult males, it is induced by endogenous testosterone decline through aging and other modifiable factors. Recent publications suggested the importance of the magnitude of longitudinal decline of testosterone from baseline. The baseline level and the longitudinal decline have individual variability influenced by individual factors including digit ratio, CAG repeat of the androgen receptor and sirtuin activity. Regarding treatment for testosterone deficiency, testosterone replacement therapy is the gold standard for the management of testosterone-deficient patients, and it improves three domains of testosterone deficiency symptoms, such as the physical, psychological and sexual domain. Recent reports suggested the importance of modifiable factors in the testosterone decline in addition to aging. Therefore, it might be responsible for the prevention of testosterone deficiency symptoms to maintain testosterone secretion taking account of the modifiable factors. The present article reviews the literature, and introduces contemporary perspectives and management of testosterone deficiency.

  11. Quantum Tunneling in Testosterone 6β-Hydroxylation by Cytochrome P450: Reaction Dynamics Calculations Employing Multiconfiguration Molecular-Mechanical Potential Energy Surfaces

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Lin, Hai

    2009-05-01

    Testosterone hydroxylation is a prototypical reaction of human cytochrome P450 3A4, which metabolizes about 50% of oral drugs on the market. Reaction dynamics calculations were carried out for the testosterone 6β-hydrogen abstraction and the 6β-d1-testosterone 6β-duterium abstraction employing a model that consists of the substrate and the active oxidant compound I. The calculations were performed at the level of canonical variational transition state theory with multidimensional tunneling and were based on a semiglobal full-dimensional potential energy surface generated by the multiconfiguration molecular mechanics technique. The tunneling coefficients were found to be around 3, indicating substantial contributions by quantum tunneling. However, the tunneling made only modest contributions to the kinetic isotope effects. The kinetic isotope effects were computed to be about 2 in the doublet spin state and about 5 in the quartet spin state.

  12. Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer.

    PubMed

    Yu, Evan Y; Getzenberg, Robert H; Coss, Christopher C; Gittelman, Marc M; Keane, Thomas; Tutrone, Ronald; Belkoff, Laurence; Given, Robert; Bass, Joel; Chu, Franklin; Gambla, Michael; Gaylis, Franklin; Bailen, James; Hancock, Michael L; Smith, Jordan; Dalton, James T; Steiner, Mitchell S

    2015-02-01

    A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course. To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy. Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot. GTx-758 and leuprolide. The primary end point was the proportion of patients achieving total testosterone ≤ 50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels. Of 159 randomized patients, leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [p<0.001], GTx-758 2000 mg [p=0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%). Although leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs. This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher

  13. Associations of cortisol/testosterone and cortisol/sex hormone-binding globulin ratios with atherosclerosis in middle-age women.

    PubMed

    Lee, Ju-Mi; Colangelo, Laura A; Schwartz, Joseph E; Yano, Yuichiro; Siscovick, David S; Seeman, Teresa; Schreiner, Pamela J; Liu, Kiang J; Lloyd-Jones, Donald M; Greenland, Philip

    2016-05-01

    The cortisol/testosterone (C/T) ratio has been hypothesized to be a better predictor of atherosclerosis than cortisol alone. No study has assessed whether the C/T and C/sex hormone-binding globulin (SHBG) ratios are associated with atherosclerosis in a U.S. population sample. This substudy included 367 women who had both cortisol from year 15 and testosterone and SHBG at year 16 of the Coronary Artery Risk Development in Young Adults study, an ongoing observational cohort in the United States. Of these, intima-media thickness (IMT) was available at follow-up year 20 in 339 (n = 332 with measurement at carotid bulb), and 303 were free of prevalent coronary artery calcium (CAC) at year 15. Area under the curve (AUC) of salivary cortisol was available in 302 individuals. Ratios of AUCs of cortisol to total testosterone, free testosterone, and SHBG were categorized into tertiles. Associations with CAC and IMT were assessed by regression models adjusted for age, race, body mass index, systolic blood pressure, menopause, oral contraceptive use, diabetes, alcohol, and smoking. Only the highest tertile of the AUC/free testosterone ratio was positively associated with carotid bulb IMT (β = 0.088, P = 0.006). This tertile was also positively associated with new onset CAC between year 15 and 25 (OR 3.45, 95% CI 1.18-10.06). Tertiles of cortisol or testosterone alone were not associated with new onset CAC. AUC/Free testosterone ratio may be more associated with atherosclerosis in women than either indicator alone. The ratio may serve as a suitable biomarker of cortisol-linked stress. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  14. Estimating age-specific trends in circulating testosterone and sex hormone-binding globulin in males and females across the lifespan.

    PubMed

    Handelsman, David J; Sikaris, Ken; Ly, Lam P

    2016-05-01

    Age-specific trends of serum testosterone and sex hormone-binding globulin across the full lifespan have not been reported. We deduced age-specific trends in serum testosterone and sex hormone-binding globulin in males and females between ages 10 and 90 from a large sample of consecutive results from a single large pathology laboratory. Coded results of 110,712 consecutive blood samples requesting serum testosterone over seven years (2007-2013) comprising blood testosterone, sex hormone-binding globulin and calculated free testosterone together with gender and age were analysed create smoothed age-specific centiles (2.5%, 5%, 25%, 50%, 75%, 95%, 97.5%) for males and females. These identified the pubertal increases in serum testosterone in males peaking at 20 years of age and remaining stable thereafter until the eighth decade. In females, circulating testosterone peaked in late adolescence and declined gradually over the next two decades but remained stable across menopause and beyond. After early childhood, serum sex hormone-binding globulin declines to a nadir in males at the age of 20 years and remains stable till the sixth decade with a gradual, progressive rise thereafter. In females, the sex hormone-binding globulin nadir is reached earlier with levels rising gradually and progressively with age thereafter and accelerating after the age of 70 years. Females also exhibit a second sex hormone-binding globulin peak during reproductive ages reflected only in upper centiles due to effects of pregnancy and oral contraceptive use in a significant minority of females. This large sample of clinical data provides a comprehensive profile of androgen status across the lifespan from early adolescence to late old age. © The Author(s) 2015.

  15. Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency.

    PubMed

    Cheetham, T Craig; An, JaeJin; Jacobsen, Steven J; Niu, Fang; Sidney, Stephen; Quesenberry, Charles P; VanDenEeden, Stephen K

    2017-04-01

    Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events. To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency. A retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012. Any prescribed TRT given by injection, orally, or topically. The primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics. The cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0

  16. Reactive oxygen species: players in the cardiovascular effects of testosterone.

    PubMed

    Tostes, Rita C; Carneiro, Fernando S; Carvalho, Maria Helena C; Reckelhoff, Jane F

    2016-01-01

    Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. Copyright © 2016 the American Physiological Society.

  17. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc.

  18. The role of testosterone in the metabolic syndrome: a review.

    PubMed

    Saad, Farid; Gooren, Louis

    2009-03-01

    Over the last three decades it has become apparent that testosterone plays a significant role in the maintenance of bone and muscle mass, in erythropoiesis, and in mental functions. But testosterone is also a key player in glucose homeostasis and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to late onset diabetes mellitus, atherosclerosis and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, glucose intolerance, raised blood pressure and dyslipidaemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol),and a pro-inflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin(SHBG) predict a higher incidence of the metabolic syndrome. There is now evidence to argue that hypotestosteronaemia should be an element in the definition of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses the unfavorable risk profile for the development of diabetes and atherosclerosis. Testosterone should be regarded as a pivotal hormone for men's health.

  19. Reactive oxygen species: players in the cardiovascular effects of testosterone

    PubMed Central

    Carneiro, Fernando S.; Carvalho, Maria Helena C.; Reckelhoff, Jane F.

    2015-01-01

    Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID:26538238

  20. Lighting conditions affect testosterone feedback sensitivity in castrated rats.

    PubMed

    Porkka-Heiskanen, T; Laakso, M L; Stenberg, D; Johansson, G; Peder, M

    1989-01-01

    It has been shown in the Syrian hamster that a short photoperiod sensitizes the hypothalamo-hypophyseal axis of castrated animals to the negative feedback effect of testosterone. There is some evidence that even the reproductive system of the rat, which is generally considered not to be very sensitive to light, can respond to changes in illumination. Therefore, we found it of interest to examine whether alterations in lighting conditions produce changes of sensitivity in the negative feedback effect of testosterone in the rat. We kept intact, castrated, and castrated testosterone-treated animals either in periodic (L:D 12:12) or constant light for 7 days starting 4 weeks after castration. In all 3 testosterone-injected groups, serum luteinizing hormone (LH) was lower in constant than in periodic light. Exogenous testosterone did not decrease the castration-induced elevations of pituitary LH and follicle-stimulating hormone (FSH). On the contrary, testosterone increased the pituitary contents of LH and FSH, especially in constant light. We conclude that, in constant light, the hypothalamo-hypophyseal axis of the castrated rat becomes more sensitive to the negative feedback action of testosterone.

  1. Testosterone and temperament traits in men: Longitudinal analysis.

    PubMed

    Määttänen, Ilmari; Jokela, Markus; Hintsa, Taina; Firtser, Sonja; Kähönen, Mika; Jula, Antti; Raitakari, Olli T; Keltikangas-Järvinen, Liisa

    2013-10-01

    Testosterone is the main male hormone that has been associated with various behavioral traits in humans and other animals. We investigated whether levels of total testosterone, free testosterone, and sex hormone binding globulin were associated with temperament traits in a population-based sample of Finnish men at two measurement times taken 6 years apart (n=686 in year 2001, n=727 in year 2007). Temperament was assessed using the Temperament and Character Inventory that consists of four temperament traits: novelty seeking, harm avoidance, reward dependence, and persistence. Higher levels of total and free testosterone were associated with higher novelty seeking (standardized B=0.103, p<0.001). This association was also observed in a longitudinal within-person analysis (B=0.084, p=0.008), suggesting that the association is not confounded by stable between-individual differences in other characteristics. Within-individual variation in total testosterone was associated with higher reward dependence, and higher levels of free testosterone were marginally associated with higher reward dependence. Reward dependence reflects the importance of social rewards to an individual. These results provide additional evidence for the stable and time-varying associations between testosterone and temperament in humans.

  2. An exploration of testosterone levels in patients with bipolar disorder

    PubMed Central

    Wooderson, Sarah C.; Gallagher, Peter; Watson, Stuart

    2015-01-01

    Background Testosterone influences well-being, mood and cognition and may play a role in the pathophysiology of bipolar disorder. Aim To examine testosterone levels in patients with bipolar disorder compared with healthy controls. Method We examined baseline total testosterone levels and current depression scores in male and female patients with bipolar disorder and mild to moderate depression and healthy controls. Results A significant interaction between diagnosis and gender was observed (F(2,97)=9.791, P=0.002). Testosterone levels were significantly lower for male patients with bipolar disorder compared with male controls (P=0.001). Women with bipolar disorder had significantly higher testosterone levels than female controls (P=0.03). Conclusions Disturbances in testosterone levels may represent an important neurobiological abnormality in bipolar disorder and may differ by gender. If these findings are confirmed, the use of gender appropriate treatment strategies for the normalisation of testosterone levels in bipolar disorder depression should be further explored. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703738

  3. Testosterone and muscle hypertrophy in female rats

    NASA Technical Reports Server (NTRS)

    Kuhn, F. E.; Max, S. R.

    1985-01-01

    The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

  4. Testosterone and muscle hypertrophy in female rats

    NASA Technical Reports Server (NTRS)

    Kuhn, F. E.; Max, S. R.

    1985-01-01

    The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

  5. Problematic chemical shifts of a fluorine-labeled surfactant and oil in some microemulsion systems. [Soap is potassium 11-(2,2,2-trifluoroethoxy)undecanoate oil is 1-(2,2,2-trifluoroethoxy)hexane or a mixture of this material with heptane

    SciTech Connect

    Muller, N.

    1982-05-27

    Fluorine chemical shifts are reported for water/oil/soap/butanol microemulsions in which the soap is potassium 11-(2,2,2-trifluoroethoxy)undecanoate and the oil is 1-(2,2,2-trifluoroethoxy)hexane or a mixture of this material with heptane. In many of the solutions the two fluorinated compounds appear to have identical microenvironments. This reinforces arguments presented recently by others to the effect that microemulsions do not always contain distinct oil-rich and water-rich domains separated by a well-defined interfacial layer.

  6. Management of erectile dysfunction by combination therapy with testosterone and sildenafil in recipients of high-dose therapy for haematological malignancies.

    PubMed

    Chatterjee, R; Kottaridis, P D; McGarrigle, H H; Linch, D C

    2002-04-01

    Erectile dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg of sildenafil orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant.

  7. TESTOSTERONE AS A DISCRIMINATIVE STIMULUS IN MALE RATS

    PubMed Central

    Wood, Ruth I.; Vertelkina, Nina V.; Antzoulatos, Eleni

    2011-01-01

    Testosterone and other anabolic-androgenic steroids (AAS) are reinforcing in animals, as determined by conditioned place preference or self-administration. Most drugs of abuse produce subjective effects on mood and perception that initiate and maintain drug taking. Whether AAS have similar effects is not known. Food-restricted male Sprague-Dawley rats (n=9) were tested for their ability to discriminate an injection of testosterone from the β-cyclodextrin vehicle using a standard two-lever operant paradigm. In drug discrimination, animals use the subjective effects of drug or vehicle to select the appropriate lever to obtain food pellets under an FR10 schedule of reinforcement. All rats demonstrated vigorous responding for food (1415.1±76.1 responses/20 min) with 94.9% of responses on the active lever. For the first 30 days, rats received 1 mg/kg testosterone sc 30 min before testing. On Day 14, one rat achieved the discrimination criteria of 9/10 consecutive days with >90% responses on the active lever and ≤5 responses on the inactive lever before the first reinforcement. Subsequently, rats were tested with testosterone at different doses (2, 7.5, 15 mg/kg at 30 min before testing) and times (2 mg/kg at 30 or 60 min before testing), each for 20 days. One additional rat demonstrated successful discrimination at Day 54 with 2 mg/kg testosterone 60 min before testing. The remaining 7 rats failed to discriminate testosterone within 110 days. When analyzed according to less-stringent standards, 4 additional rats met criteria for testosterone discrimination. However, continued performance was not stable. Thus, testosterone was unable to consistently support drug discrimination. We conclude that testosterone does not produce rapid interoceptive effects. (NIH DA12843 to RIW) PMID:21893083

  8. Second to fourth digit ratio, testosterone and perceived male dominance.

    PubMed

    Neave, Nick; Laing, Sarah; Fink, Bernhard; Manning, John T

    2003-10-22

    Previous studies have shown that male faces with extreme features associated with testosterone are perceived as dominant and masculine. Women have been reported to prefer more masculinized male faces as they may consider testosterone markers to be an 'honest' indication of good health, and such considerations may underlie their aesthetic preferences. However, pronounced testosterone facial markers are also associated with dominance, and several negative personality traits. This suggests that female aesthetic preferences may be an adaptive compromise between positive attributes associated with higher than average testosterone, and negative attributes associated with more extreme masculinization. This current study attempts to clarify the role of hormone markers in female perceptions of dominance, masculinity and attractiveness, in male facial images. Recent evidence suggests that the relative length of the 2nd to 4th finger (2D : 4D ratio) is a pointer to prenatal testosterone levels and may thus serve as a window to the prenatal hormonal environment. We measured 2D : 4D in a sample of male college students and took salivary samples to analyse circulating levels of testosterone. Women rated facial images of these males for dominance, masculinity and attractiveness. Our results show that male 2D : 4D was significantly negatively related to perceived dominance and masculinity but not attractiveness. Circulating testosterone levels were not related to dominance, masculinity or attractiveness. These findings suggest that: (i) high prenatal levels of testosterone serve to 'organize' male facial features to subsequently reflect dominance and masculine characteristics presumably activated during puberty; and (ii) attractiveness is not directly related to testosterone levels. We conclude that facial dominance and masculinity reflect a male's perceived status rather than his physical attraction to women.

  9. Second to fourth digit ratio, testosterone and perceived male dominance.

    PubMed Central

    Neave, Nick; Laing, Sarah; Fink, Bernhard; Manning, John T

    2003-01-01

    Previous studies have shown that male faces with extreme features associated with testosterone are perceived as dominant and masculine. Women have been reported to prefer more masculinized male faces as they may consider testosterone markers to be an 'honest' indication of good health, and such considerations may underlie their aesthetic preferences. However, pronounced testosterone facial markers are also associated with dominance, and several negative personality traits. This suggests that female aesthetic preferences may be an adaptive compromise between positive attributes associated with higher than average testosterone, and negative attributes associated with more extreme masculinization. This current study attempts to clarify the role of hormone markers in female perceptions of dominance, masculinity and attractiveness, in male facial images. Recent evidence suggests that the relative length of the 2nd to 4th finger (2D : 4D ratio) is a pointer to prenatal testosterone levels and may thus serve as a window to the prenatal hormonal environment. We measured 2D : 4D in a sample of male college students and took salivary samples to analyse circulating levels of testosterone. Women rated facial images of these males for dominance, masculinity and attractiveness. Our results show that male 2D : 4D was significantly negatively related to perceived dominance and masculinity but not attractiveness. Circulating testosterone levels were not related to dominance, masculinity or attractiveness. These findings suggest that: (i) high prenatal levels of testosterone serve to 'organize' male facial features to subsequently reflect dominance and masculine characteristics presumably activated during puberty; and (ii) attractiveness is not directly related to testosterone levels. We conclude that facial dominance and masculinity reflect a male's perceived status rather than his physical attraction to women. PMID:14561281

  10. Mouse Spermatogenesis Requires Classical and Nonclassical Testosterone Signaling1

    PubMed Central

    Toocheck, Corey; Clister, Terri; Shupe, John; Crum, Chelsea; Ravindranathan, Preethi; Lee, Tae-Kyung; Ahn, Jung-Mo; Raj, Ganesh V.; Sukhwani, Meena; Orwig, Kyle E.; Walker, William H.

    2015-01-01

    Testosterone acts though the androgen receptor in Sertoli cells to support germ cell development (spermatogenesis) and male fertility, but the molecular and cellular mechanisms by which testosterone acts are not well understood. Previously, we found that in addition to acting through androgen receptor to directly regulate gene expression (classical testosterone signaling pathway), testosterone acts through a nonclassical pathway via the androgen receptor to rapidly activate kinases that are known to regulate spermatogenesis. In this study, we provide the first evidence that nonclassical testosterone signaling occurs in vivo as the MAP kinase cascade is rapidly activated in Sertoli cells within the testis by increasing testosterone levels in the rat. We find that either classical or nonclassical signaling regulates testosterone-mediated Rhox5 gene expression in Sertoli cells within testis explants. The selective activation of classical or nonclassical signaling pathways in Sertoli cells within testis explants also resulted in the differential activation of the Zbtb16 and c-Kit genes in adjacent spermatogonia germ cells. Delivery of an inhibitor of either pathway to Sertoli cells of mouse testes disrupted the blood-testis barrier that is essential for spermatogenesis. Furthermore, an inhibitor of nonclassical testosterone signaling blocked meiosis in pubertal mice and caused the loss of meiotic and postmeiotic germ cells in adult mouse testes. An inhibitor of the classical pathway caused the premature release of immature germ cells. Collectively, these observations indicate that classical and nonclassical testosterone signaling regulate overlapping and distinct functions that are required for the maintenance of spermatogenesis and male fertility. PMID:26607719

  11. Testim 1% testosterone gel for the treatment of male hypogonadism.

    PubMed

    Bouloux, Pierre

    2005-03-01

    The aim of this work was to review the pharmacokinetic and clinical profile of Testim (Auxilium Pharmaceuticals, Norristown, Pennsylvania) 1% gel formulation of testosterone for the treatment of male hypogonadism. An English-language search of the medical literature was conducted using PubMed (1998-December 2004) and EMBASE (1998-December 2004). Search terms included ag(e)ing male, male hypogonadism, late-onset hypogonadism, testosterone, testosterone deficiency, testosterone therapy, testosterone replacement therapy, androgen therapy, testosterone gel, and Testim. Bibliographies of retrieved articles were also reviewed. Five published clinical studies were reviewed. Testim 50 mg showed clear pharmacokinetic differences from AndroGel (known as Testogel in Europe; Unimed Pharmaceuticals, Inc., and Solvay Pharmaceuticals, Inc., Marietta, Georgia) 1% testosterone gel 50 mg, with increases of 30% (90% CI, 8%-57%) and 47% (90% CI, 20%-79%) versus AndroGel, respectively, in AUC(0-24h) for total serum testosterone and free testosterone. In a 30-day study of 638 men with hypogonadism, sexual desire scores and sexual motivation scores increased after Testim treatment at weeks 1, 2, 3, and 4 (each, P < 0.001). During 12 months of treatment with Testim 50 or 100 mg in 371 men with hypogonadism, total serum testosterone levels were raised to and maintained within the normal adult range, lean body mass increased by 2.2 kg (P < 0.001), fat mass fell by 2.1% (P < 0.001), and bone mineral density increased by 2.58% (P < 0.001). Mean scores for sexual desire, performance, motivation, and spontaneous erections were all significantly higher (all, P < 0.001) than at baseline for all time points during 12-month studies of Testim. In 2 studies comparing Testim with different testosterone patches, treatment with the gel resulted in 10-fold fewer application-site reactions than either patch. In men with hypogonadism, Testim gel raised and maintained serum testosterone levels to within the

  12. The endocrine pharmacology of testosterone therapy in men

    NASA Astrophysics Data System (ADS)

    Oettel, Michael

    The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discussion of congenital androgen deficiency in young men is followed by methods of diagnosing hypogonadism in older men. Among therapeutic options, the alternatives to direct testosterone replacement are discussed, although none of them have proved to be particularly successful in clinical practice. For testosterone replacement itself, various routes of administration and pharmaceutical formulations are now available, facilitating good monitoring and individualized therapy.

  13. [Testosterone therapy in female hypoactive sexual desire disorder].

    PubMed

    Meyer, Patrick

    2016-03-16

    Hypoactive sexual desire disorder (HSDD) is a deficiency of sexual desire that causes marked personal or interpersonal distress. It occurs in approximately 1 in 10 adult women. A number of potential contributory factors (hormonal, neurobiological and psychosocial) have been identified. Testosterone plays an excitatory role in sexual desire but the mechanism is not yet well understood. Treatment with testosterone has been shown to improve sexual desire in menopausal women with HSDD. However, there are limited data concerning premenopausal women and long-term safety. At present, physiological testosterone preparations for use in women are not available in Switzerland.

  14. Late-Onset Hypogonadism and Testosterone Replacement in Older Men.

    PubMed

    Bhattacharya, Rajib K; Bhattacharya, Shelley B

    2015-11-01

    Late-onset hypogonadism is an underdiagnosed and easily treated condition defined by low serum testosterone levels in men older than 65 years. When treated, a significant improvement in quality of life may be reached in this rapidly rising sector of the population. During the evaluation, laboratory tests and a full medication review should be performed to exclude other illnesses or adverse effects from medications. The major goal of treatment in this population is treating the symptoms related to hypogonadism. There has not been clear evidence supporting universally giving older men with low serum testosterone levels and hypogonadal symptoms testosterone replacement therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Synthesis of deuterium labeled 17-methyl-testosterone

    SciTech Connect

    Shinohara, Y.; Baba, S.; Kasuya, Y.

    1984-09-01

    The synthesis of two forms of selectively deuterated 17-methyl-testosterone is described. 17-Methyl-d3-testosterone was prepared by the Grignard reaction of dehydroepiandrosterone with deuterium labeled methyl magnesium iodide followed by an Oppenauer oxidation. 17-Methyl-d3-testosterone-19,19,19-d3 was prepared by treating 3,3-ethylenedioxy-5,10-epoxy-5 alpha, 10 alpha-estran-17-one with deuterium labeled methyl magnesium bromide followed by hydrolysis and dehydration of the 5 alpha-hydroxyandrostane derivative.

  16. Testosterone treatment in the aging male: myth or reality?

    PubMed

    Nigro, Nicole; Christ-Crain, Mirjam

    2012-03-19

    The definition of late onset hypogonadism in the aging male is controversially debated, and according to the latest literature consists of at least three especially sexual symptoms such as loss of morning erection, low sexual desire and erectile dysfunction as well as a total testosterone <8-11 nmol/l. Testosterone replacement therapy in the aging male has been shown to have a beneficial effect on muscle and fat mass as well as on bone mineral density, with more conflicting effects observed on muscle strength, sexual function, mood and quality of life. The prescriptions for testosterone products for the aging male increased by over 170% in the previous five years. Furthermore, there is a lot of epidemiological data showing an inverse relationship between testosterone levels and obesity, insulin resistance, the metabolic syndrome and type 2 diabetes mellitus. However, only few small randomised placebo-controlled studies have investigated the effect of testosterone replacement therapy on insulin resistance and HbA1c levels, with controversial results. Importantly, so far the long-term safety and efficacy of testosterone replacement therapy has not been established. Although until now no clear evidence has been found that testosterone replacement therapy has a causative role in prostate cancer or indeed in changes of the biology of the prostate, in a recent meta-analysis a 4-fold increased risk of prostate-associated event rates in testosterone treated elderly men sounds a note of caution. Also the risk for cardiovascular events is still not clear and caution is warranted especially in elderly men with cardiovascular disease and limited mobility. In summary, the actual available evidence of long-term risks and outcome of testosterone replacement therapy is still very limited and carefully designed placebo-controlled trials of testosterone administration to assess the risks and benefits of such a therapy are required. Until then, testosterone treatment in elderly men

  17. Testosterone vs. aromatase inhibitor in older men with low testosterone: effects on cardiometabolic parameters.

    PubMed

    Dias, J P; Shardell, M D; Carlson, O D; Melvin, D; Caturegli, G; Ferrucci, L; Chia, C W; Egan, J M; Basaria, S

    2017-01-01

    Testosterone (T) replacement is being increasingly offered to older men with age-related decline in testosterone levels. The effects of long-term testosterone replacement and aromatase inhibition (AI) on glucose homeostasis and cardiometabolic markers were determine in older non-diabetic men with low testosterone levels. Men ≥65 years, mean age 71 ± 3 years with serum total T < 350 ng/dL were randomized in a double-blind, placebo-controlled, parallel-group, proof-of-concept trial evaluating the effects of 5 g transdermal testosterone gel (TT) (n = 10), 1 mg anastrozole (n = 10) or placebo (n = 9) daily for 12 months. Homeostatic Model Assessment of insulin resistance (HOMAIR ) was the primary outcome. Secondary outcomes included OGIS in response to OGTT, fasting lipids, C-reactive protein (CRP), adipokines, and abdominal and mid-thigh fat by computed tomography. All outcomes were assessed at baseline and 12 months. After 12 months, absolute changes in HOMAIR in both treatment arms (TT group: -0.05 ± 0.21); (AI group: 0.15 ± 0.10) were similar to placebo (-0.11 ± 0.26), as were CRP and fasting lipid levels. Adiponectin levels significantly decreased in the TT group (-1.8 ± 0.9 mg/L, p = 0.02) and abdominal subcutaneous fat (-60.34 ± 3.19 cm(2) , p = 0.003) and leptin levels (-1.5 ± 1.2 ng/mL, p = 0.04) were significantly lower with AI. Mid-thigh subcutaneous fat was reduced in both treatment arms (TT group: -4.88 ± 1.24 cm(2) , p = 0.008); (AI group: -6.05 ± 0.87 cm(2) , p = 0.0002). In summary, in this proof-of-concept trial, changes in HOMAIR AI were similar in all three groups while the effects of intervention on subcutaneous fat distribution and adipokines were variable. Larger efficacy and safety trials are needed before AI pharmacotherapy can be considered as a treatment option for low T levels in older men.

  18. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment

    PubMed Central

    Resnick, Susan M.; Matsumoto, Alvin M.; Stephens-Shields, Alisa J.; Ellenberg, Susan S.; Gill, Thomas M.; Shumaker, Sally A.; Pleasants, Debbie D.; Barrett-Connor, Elizabeth; Bhasin, Shalender; Cauley, Jane A.; Cella, David; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Farrar, John T.; Lewis, Cora E.; Molitch, Mark E.; Pahor, Marco; Swerdloff, Ronald S.; Cifelli, Denise; Anton, Stephen; Basaria, Shehzad; Diem, Susan J.; Wang, Christina; Hou, Xiaoling; Snyder, Peter J.

    2017-01-01

    Importance Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. Objective To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI). Design, Setting, and Participants The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014. Interventions Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year. Main Outcomes and Measures The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to −26), executive function (Trail-Making Test B minus A; range, −290 to 290), and spatial ability (Card Rotation Test; score range, −80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months. Results Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the

  19. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment.

    PubMed

    Resnick, Susan M; Matsumoto, Alvin M; Stephens-Shields, Alisa J; Ellenberg, Susan S; Gill, Thomas M; Shumaker, Sally A; Pleasants, Debbie D; Barrett-Connor, Elizabeth; Bhasin, Shalender; Cauley, Jane A; Cella, David; Crandall, Jill P; Cunningham, Glenn R; Ensrud, Kristine E; Farrar, John T; Lewis, Cora E; Molitch, Mark E; Pahor, Marco; Swerdloff, Ronald S; Cifelli, Denise; Anton, Stephen; Basaria, Shehzad; Diem, Susan J; Wang, Christina; Hou, Xiaoling; Snyder, Peter J

    2017-02-21

    Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI). The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014. Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year. The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to -26), executive function (Trail-Making Test B minus A; range, -290 to 290), and spatial ability (Card Rotation Test; score range, -80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months. Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean

  20. A sex-specific dose-response curve for testosterone: could excessive testosterone limit sexual interaction in women?

    PubMed

    Krapf, Jill M; Simon, James A

    2017-04-01

    Testosterone treatment increases sexual desire and well-being in women with hypoactive sexual desire disorder; however, many studies have shown only modest benefits limited to moderate doses. Unlike men, available data indicate women show a bell-shaped dose-response curve for testosterone, wherein a threshold dosage of testosterone leads to desirable sexual function effects, but exceeding this threshold results in a lack of further positive sexual effects or may have a negative impact. Emotional and physical side-effects of excess testosterone, including aggression and virilization, may counteract the modest benefits on sexual interaction, providing a possible explanation for a threshold dose of testosterone in women. In this commentary, we will review and critically analyze data supporting a curvilinear dose-response relationship between testosterone treatment and sexual activity in women with low libido, and also explore possible explanations for this observed relationship. Understanding optimal dosing of testosterone unique to women may bring us one step closer to overcoming regulatory barriers in treating female sexual dysfunction.

  1. Protective effect of royal jelly on the sperm parameters and testosterone level and lipid peroxidation in adult mice treated with oxymetholone

    PubMed Central

    Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid; Heidari, Reza

    2014-01-01

    Objectives : The aim of the present study was to evaluate protective effect of royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA) production in mice. Materials and Methods: Thirty-two adult male NMRI mice weighing 30±2 g were used. All the animals were divided into 4 groups. Control group: received saline 0.1 ml/mouse/day orally for 30 days. Royal jelly group (RJ): received royal jelly at dose of 100 mg/kg daily for 30 days orally. Oxymetholone group: the received Oxymetholone (OX) at dose of 5 mg/kg daily for 30 days orally. Royal jelly+Oxymetholone group: received royal jelly at dose of 100 mg/kg/day orally concomitant with OX administration. Sperm count, sperm motility, viability, maturity, and DNA integrity were analyzed. Furthermore, serum testosterone and MDA concentrations were determined. Results: In Oxymetholone group, sperm count, motility as well as testosterone concentration reduced significantly (p<0.05), while significant (p<0.05) increases in immature sperm, sperm with DNA damaged, and MDA concentration were announced in Oxymetholone group in comparison with control group and Royal jelly+Oxymetholone group. RJ caused partially amelioration in all of the above- mentioned parameters in Royal Jelly+Oxymetholone group. Conclusion: In conclusion, RJ may be used in combination with OX to improve OX-induced oxidative stress and male infertility. PMID:25050300

  2. Gender differences in financial risk aversion and career choices are affected by testosterone

    PubMed Central

    Sapienza, Paola; Zingales, Luigi; Maestripieri, Dario

    2009-01-01

    Women are generally more risk averse than men. We investigated whether between- and within-gender variation in financial risk aversion was accounted for by variation in salivary concentrations of testosterone and in markers of prenatal testosterone exposure in a sample of >500 MBA students. Higher levels of circulating testosterone were associated with lower risk aversion among women, but not among men. At comparably low concentrations of salivary testosterone, however, the gender difference in risk aversion disappeared, suggesting that testosterone has nonlinear effects on risk aversion regardless of gender. A similar relationship between risk aversion and testosterone was also found using markers of prenatal testosterone exposure. Finally, both testosterone levels and risk aversion predicted career choices after graduation: Individuals high in testosterone and low in risk aversion were more likely to choose risky careers in finance. These results suggest that testosterone has both organizational and activational effects on risk-sensitive financial decisions and long-term career choices. PMID:19706398

  3. Long-acting contraceptive agents: testosterone esters of unsaturated acids.

    PubMed

    Francisco, C G; Freire, R; Gawronski, J; Hernández, R; Kielczewski, M; Salazar, J A; Savabi, F; Shafiee, A; Strekowski, L; Suárez, E

    1990-01-01

    The synthesis of 13 new esters of testosterone is described, with the esterifying acids bearing acetylenic, olefinic, or polyunsaturated functions in the chain, for evaluation as long-acting androgens.

  4. On the effects of testosterone on brain behavioral functions

    PubMed Central

    Celec, Peter; Ostatníková, Daniela; Hodosy, Július

    2015-01-01

    Testosterone influences the brain via organizational and activational effects. Numerous relevant studies on rodents and a few on humans focusing on specific behavioral and cognitive parameters have been published. The results are, unfortunately, controversial and puzzling. Dosing, timing, even the application route seem to considerably affect the outcomes. In addition, the methods used for the assessment of psychometric parameters are a bit less than ideal regarding their validity and reproducibility. Metabolism of testosterone contributes to the complexity of its actions. Reduction to dihydrotestosterone by 5-alpha reductase increases the androgen activity; conversion to estradiol by aromatase converts the androgen to estrogen activity. Recently, the non-genomic effects of testosterone on behavior bypassing the nuclear receptors have attracted the interest of researchers. This review tries to summarize the current understanding of the complexity of the effects of testosterone on brain with special focus on their role in the known sex differences. PMID:25741229

  5. Genetic Polymorphisms Related to Testosterone Metabolism in Intellectually Gifted Boys

    PubMed Central

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; Ostatníková, Daniela

    2013-01-01

    Prepubertal testosterone levels are lower in intellectually gifted boys. The aim of this pilot study was to analyze potential genetic factors related to testosterone metabolism in control and gifted boys. Intellectually gifted (IQ>130; n = 95) and control (n = 67) boys were genotyped. Polymorphisms of interests were chosen in genes including androgen and estrogen receptors, 5-alpha reductase, aromatase and sex hormone binding globulin. Significant differences between control and gifted boys in genotype distributions were found for ESR2 (rs928554) and SHBG (rs1799941). A significantly lower number of CAG repeats in the AR gene were found in gifted boys. Our results support the role of genetic factors related to testosterone metabolism in intellectual giftedness. Increased androgen signaling might explain previous results of lower testosterone levels in intellectually gifted boys and add to the understanding of variability in cognitive abilities. PMID:23382957

  6. Genetic polymorphisms related to testosterone metabolism in intellectually gifted boys.

    PubMed

    Celec, Peter; Tretinárová, Denisa; Minárik, Gabriel; Ficek, Andrej; Szemes, Tomáš; Lakatošová, Silvia; Schmidtová, Eva; Turňa, Ján; Kádaši, Ľudevít; Ostatníková, Daniela

    2013-01-01

    Prepubertal testosterone levels are lower in intellectually gifted boys. The aim of this pilot study was to analyze potential genetic factors related to testosterone metabolism in control and gifted boys. Intellectually gifted (IQ>130; n = 95) and control (n = 67) boys were genotyped. Polymorphisms of interests were chosen in genes including androgen and estrogen receptors, 5-alpha reductase, aromatase and sex hormone binding globulin. Significant differences between control and gifted boys in genotype distributions were found for ESR2 (rs928554) and SHBG (rs1799941). A significantly lower number of CAG repeats in the AR gene were found in gifted boys. Our results support the role of genetic factors related to testosterone metabolism in intellectual giftedness. Increased androgen signaling might explain previous results of lower testosterone levels in intellectually gifted boys and add to the understanding of variability in cognitive abilities.

  7. Testosterone Therapy May Be Linked to Serious Blood Clots

    MedlinePlus

    ... testosterone pills, gels or injections, hoping that the male hormone will boost their sex drive, stamina and strength. It's been known for a while that the estrogen in birth control pills increases a woman's risk of blood clots, ...

  8. A method for the estimation of urinary testosterone

    PubMed Central

    Ismail, A. A. A.; Harkness, R. A.

    1966-01-01

    1. A method has been developed for the estimation of testosterone in human urine by using acid hydrolysis followed by a quantitative form of a modified Girard reaction that separates a `conjugated-ketone' fraction from a urine extract; this is followed by column chromatography on alumina and paper chromatography. 2. Comparison of methods of estimation of testosterone in the final fraction shows that estimation by gas–liquid chromatography is more reproducible than by colorimetric methods applied to the same eluates from the paper chromatogram. 3. The mean recovery of testosterone by gas–liquid chromatography is 79·5%, and this method appears to be specific for testosterone. 4. The procedure is relatively rapid. Six determinations can be performed by one worker in 2 days. 5. Results of determinations on human urine are briefly presented. In general, they are similar to earlier estimates, but the maximal values are lower. PMID:5964968

  9. Oral Cancer

    MedlinePlus

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  10. Oral myiasis.

    PubMed

    Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem

    2015-01-01

    Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  11. Oral Myiasis

    PubMed Central

    Saravanan, Thalaimalai; Mohan, Mathan A; Thinakaran, Meera; Ahammed, Saneem

    2015-01-01

    Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy. PMID:25709196

  12. The Effect of Testosterone on Men With Andropause

    PubMed Central

    Sofimajidpour, Heshmatollah; Teimoori, Taher; Gharibi, Fardin

    2015-01-01

    Background: Andropause is the gradual reduction of the male sex hormone (testosterone) with increasing age. Its symptoms are sexual dysfunction, weakness, fatigue, insomnia, loss of motivation, mood disorders and reduction of bone density. Treatment of andropause with testosterone has been recently considered. Objectives: The aim of this study was to evaluate the effect of testosterone in the treatment of andropause in men. Patients and Methods: For men who met the inclusion criteria (50 years of age and older) laboratory tests and clinical examinations were conducted by an urologist in order to diagnose prostate cancer, prostate disease, urinary tract infection and active urinary retention. After obtaining consent, the patients were enrolled in the study. Data were analyzed using SPSS version 20. Descriptive statistics (frequency and percentage, mean, standard deviation) and the paired t-test were used to compare levels of testosterone. To determine the correlation between age and testosterone levels, the Pearson correlation was used. Finally, to compare the treatment processes during the treatment period the repeated measures ANOVA was used. Results: The mean age of patients was 56.57 ± 3.21 years. A total of 31 patients (39%) were smokers, among them 30% smoked daily, 2.5% weekly and 6% smoked for fun. The mean testosterone level before treatment was 240.6 ± 125.4 and at 1, 3 and 6 months after treatment the level was raised, so that at the end of the sixth months it was 578.7 ± 141.7. The level of increase was statistically significant (P = 0.0001). Conclusions: Treatment with testosterone in men over 50 years with andropause will increase testosterone levels and also quality of life, sexual desire, erection, energy levels, ability to exercise and feel the joy of life more than before. Depression was decreased and they had sleepy feelings after dinner. PMID:26756004

  13. Supra-physiological dose of testosterone induces pathological cardiac hypertrophy.

    PubMed

    Pirompol, Prapawadee; Teekabut, Vassana; Weerachatyanukul, Wattana; Bupha-Intr, Tepmanas; Wattanapermpool, Jonggonnee

    2016-04-01

    Testosterone and androgenic anabolic steroids have been misused for enhancement of physical performance despite many reports on cardiac sudden death. Although physiological level of testosterone provided many regulatory benefits to human health, including the cardiovascular function, supra-physiological levels of the hormone induce hypertrophy of the heart with unclear contractile activation. In this study, dose- and time-dependent effects of high-testosterone treatment on cardiac structure and function were evaluated. Adult male rats were divided into four groups of testosterone treatment for 0, 5, 10, and 20 mg/kg BW for 4, 8, or 12 weeks. Increases in both percentage heart:body weight ratio and cardiomyocyte cross-sectional area in representing hypertrophy of the heart were significantly shown in all testosterone-treated groups to the same degree. In 4-week-treated rats, physiological cardiac hypertrophy was apparent with an upregulation of α-MHC without any change in myofilament contractile activation. In contrast, pathological cardiac hypertrophy was observed in 8- and 12-week testosterone-treated groups, as indicated by suppression of myofilament activation and myocardial collagen deposition without transition of MHC isoforms. Only in 12-week testosterone-treated group, eccentric cardiac hypertrophy was demonstrated with unaltered myocardial stiffness, but significant reductions in the phosphorylation signals of ERK1/2 and mTOR. Results of our study suggest that the outcome of testosterone-induced cardiac hypertrophy is not dose dependent but is rather relied on the factor of exposure to duration in inducing maladaptive responses of the heart. © 2016 Society for Endocrinology.

  14. Risks of testosterone replacement therapy in ageing men.

    PubMed

    Tan, R S; Salazar, J A

    2004-11-01

    Testosterone has been available to practitioners for several decades. However, testosterone prescriptions have increased in recent years partly because of the introduction of newer delivery systems that are topical and have good bioavailability. In the US alone, approximately 2 million prescriptions for testosterone were written in 2002. This represents a 30% increase from 2001 and a 170% increase from 1999. There has also been a 500% increase in prescription sales in the past 10 years. The rise in prescriptions may be in part due to the increasing recognition of hypogonadism in ageing males or andropause. Treatment relating to hypogonadism has relieved symptoms and improved the quality of life of many individuals. Epidemiological studies point toward an association with increased morbidity and mortality, with low testosterone states in ageing males. For example, there is a higher prevalence of depression, coronary heart disease, osteoporosis, fracture rates, frailty and even dementia with low testosterone states. Recently, there have been some concerns raised regarding the long-term safety of testosterone replacement therapy (TRT) from the Institute of Medicine. Current evidence suggests no causal relationship between prostate cancer and physiological dosing of testosterone, especially with careful selection and monitoring of patients. Cardiovascular risks have, overall, been neutral, although suggestions have been made that there are positive vasodilatory properties with testosterone. Mild eythrocytosis can be a common side effect of TRT, but thromboembolic events have rarely been reported in the literature. This paper addresses the evidence to date regarding the safety aspects of TRT. The medical-legal implications of TRT for men at this point in time is also discussed.

  15. Correlation Between Personality Traits and Testosterone Concentrations in Healthy Population

    PubMed Central

    Tajima-Pozo, Kazuhiro; Bayón, Camila; Díaz-Marsá, Marina; Carrasco, Jose Luis

    2015-01-01

    Objective: High plasma testosterone levels have been associated with aggression, sexual behaviour and social status. The aim of this paper was to study the correlation between basal plasma testosterone levels and personality variables in healthy participants. Materials and Methods: Fifty-four participants were randomly enrolled into this study. Basal plasma testosterone levels were measured between 8:30 am and 10 am. After 24 hours of blood drawing, each subject completed personality questionnaires. Results: Positive correlation between basal plasma testosterone levels and anti-social personality traits in both genders was observed (r = 0.336 and P < 0.018). Also, a positive correlation was observed between basal plasmatestosterone levels and criminal thinking traits (r = 0. 376, P < 0.05) and Millon compulsive (r = 0.386, P < 0.010) in both genders. In female participants, a positive correlation between basal plasmatestosterone levels and psychoticism (r = 0. 25, P < 0.019) and Cloninger AUTO TCI (r = 0.507, P < 0.004) was observed. In males participants positive correlation between baseline plasmatic Testosterone levels and Millon Antisocial trait (r = 0. 544, P < 0.19) and Millon Hypomania trait (r = 0. 485, P < 0.41) and Millon Drug Abuse trait (r = 0.632, P < 0.05) was reported. Conclusion: Our results suggest gender differences in clinical and personality variables related with basal plasma testosterone level. In men, high plasma testosterone levels were associated with clinical traits, substance abuse and hypomania. Women with higher basal testosterone levels showed higher scores on personality self-direction traits. PMID:26664080

  16. Correlation Between Personality Traits and Testosterone Concentrations in Healthy Population.

    PubMed

    Tajima-Pozo, Kazuhiro; Bayón, Camila; Díaz-Marsá, Marina; Carrasco, Jose Luis

    2015-01-01

    High plasma testosterone levels have been associated with aggression, sexual behaviour and social status. The aim of this paper was to study the correlation between basal plasma testosterone levels and personality variables in healthy participants. Fifty-four participants were randomly enrolled into this study. Basal plasma testosterone levels were measured between 8:30 am and 10 am. After 24 hours of blood drawing, each subject completed personality questionnaires. Positive correlation between basal plasma testosterone levels and anti-social personality traits in both genders was observed (r = 0.336 and P < 0.018). Also, a positive correlation was observed between basal plasmatestosterone levels and criminal thinking traits (r = 0. 376, P < 0.05) and Millon compulsive (r = 0.386, P < 0.010) in both genders. In female participants, a positive correlation between basal plasmatestosterone levels and psychoticism (r = 0. 25, P < 0.019) and Cloninger AUTO TCI (r = 0.507, P < 0.004) was observed. In males participants positive correlation between baseline plasmatic Testosterone levels and Millon Antisocial trait (r = 0. 544, P < 0.19) and Millon Hypomania trait (r = 0. 485, P < 0.41) and Millon Drug Abuse trait (r = 0.632, P < 0.05) was reported. Our results suggest gender differences in clinical and personality variables related with basal plasma testosterone level. In men, high plasma testosterone levels were associated with clinical traits, substance abuse and hypomania. Women with higher basal testosterone levels showed higher scores on personality self-direction traits.

  17. Mechanism of Testosterone Deficiency in the Transgenic Sickle Cell Mouse

    PubMed Central

    Musicki, Biljana; Zhang, Yuxi; Chen, Haolin; Brown, Terry R.; Zirkin, Barry R.; Burnett, Arthur L.

    2015-01-01

    Testosterone deficiency is associated with sickle cell disease (SCD), but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle) exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH) levels compared with wild type (WT) mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol)- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR), but not cholesterol side-chain cleavage enzyme (P450scc), in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi) exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease. PMID:26023917

  18. Mechanism of testosterone deficiency in the transgenic sickle cell mouse.

    PubMed

    Musicki, Biljana; Zhang, Yuxi; Chen, Haolin; Brown, Terry R; Zirkin, Barry R; Burnett, Arthur L

    2015-01-01

    Testosterone deficiency is associated with sickle cell disease (SCD), but its underlying mechanism is not known. We investigated the possible occurrence and mechanism of testosterone deficiency in a mouse model of human SCD. Transgenic sickle male mice (Sickle) exhibited decreased serum and intratesticular testosterone and increased luteinizing hormone (LH) levels compared with wild type (WT) mice, indicating primary hypogonadism in Sickle mice. LH-, dbcAMP-, and pregnenolone- (but not 22-hydroxycholesterol)- stimulated testosterone production by Leydig cells isolated from the Sickle mouse testis was decreased compared to that of WT mice, implying defective Leydig cell steroidogenesis. There also was reduced protein expression of steroidogenic acute regulatory protein (STAR), but not cholesterol side-chain cleavage enzyme (P450scc), in the Sickle mouse testis. These data suggest that the capacity of P450scc to support testosterone production may be limited by the supply of cholesterol to the mitochondria in Sickle mice. The sickle mouse testis exhibited upregulated NADPH oxidase subunit gp91phox and increased oxidative stress, measured as 4-hydroxy-2-nonenal, and unchanged protein expression of an antioxidant glutathione peroxidase-1. Mice heterozygous for the human sickle globin (Hemi) exhibited intermediate hypogonadal changes between those of WT and Sickle mice. These results demonstrate that testosterone deficiency occurs in Sickle mice, mimicking the human condition. The defects in the Leydig cell steroidogenic pathway in Sickle mice, mainly due to reduced availability of cholesterol for testosterone production, may be related to NADPH oxidase-derived oxidative stress. Our findings suggest that targeting testicular oxidative stress or steroidogenesis mechanisms in SCD offers a potential treatment for improving phenotypic changes associated with testosterone deficiency in this disease.

  19. Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats.

    PubMed

    Jeon, Woo-Young; Kim, Ohn Soon; Seo, Chang-Seob; Jin, Seong Eun; Kim, Jung-Ae; Shin, Hyeun-Kyoo; Kim, Yong-Ung; Lee, Mee-Young

    2017-08-03

    Benign prostatic hyperplasia (BPH) is non-cancerous condition of enlargement of the prostate, a common occurrence in older men. The immature fruits of Poncirus trifoliata (L.) Rafinesque (Rutaceae), Ponciri Fructus are widely used in traditional oriental medicine for the therapy of various diseases. However, little is known about the mechanism underlying the pathogenesis of BPH. In the present study, we investigated the protective effects of a Ponciri Fructus extract (PFE) on the development of BPH in a in a rat model of BPH induced by testosterone propionate (TP). Male Sprague Dawley rats were used as a model of BPH after its induction by daily subcutaneous injections of TP/corn oil, for a period of four weeks. PFE was administrated daily 1 h before TP/corn oil injection by oral gavage at a dose level of 200 mg/kg during the 4 weeks of TP/corn oil injections. All rats were sacrificed at the end of the experiment, we measured the relative prostate weight, the levels of testosterone and dihydrotestosterone (DHT), histological changes, activities of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase), and expression of proliferating cell nuclear antigen (PCNA). In addition, we also measured the inhibition (%) of 5α-reductase in the prostatic tissue. Our findings indicate that PFE significantly inhibited the development of BPH; decreased the relative prostate weight, the level of testosterone and DHT in serum and prostatic tissue, prostatic hyperplasia, expression of PCNA, and increased the antioxidant enzymes. Moreover, PFE showed a weak inhibitory activity on 5α-reductase. These results suggest that PFE may be used as a therapeutic agent for BPH via antiproliferative and antioxidant effects.

  20. Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

    PubMed Central

    Lee, Mee-Young; Shin, In-Sik; Seo, Chang-Seob; Lee, Nam-Hun; Ha, Hye-Kyung; Son, Jong-Keun; Shin, Hyeun-Kyoo

    2012-01-01

    Benign prostatic hyperplasia (BPH) is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract (MFME) improves BPH, using the testosterone propionate (TP)-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP (3 mg kg−1) dissolved in corn oil, for 4 weeks. MFME was administered daily by oral gavage at a dose of 200 mg kg−1 for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight (prostate/body weight ratio) was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone (DHT) in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound(s) responsibility for inducing the protective effect against BPH and determine its mechanism of action. PMID:22231294

  1. Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats.

    PubMed

    Lee, Mee-Young; Shin, In-Sik; Seo, Chang-Seob; Lee, Nam-Hun; Ha, Hye-Kyung; Son, Jong-Keun; Shin, Hyeun-Kyoo

    2012-03-01

    Benign prostatic hyperplasia (BPH) is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract (MFME) improves BPH, using the testosterone propionate (TP)-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP (3 mg kg(-1)) dissolved in corn oil, for 4 weeks. MFME was administered daily by oral gavage at a dose of 200 mg kg(-1) for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight (prostate/body weight ratio) was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone (DHT) in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound(s) responsibility for inducing the protective effect against BPH and determine its mechanism of action.

  2. The benefits and risks of testosterone replacement therapy: a review

    PubMed Central

    Bassil, Nazem; Alkaade, Saad; Morley, John E

    2009-01-01

    Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT) treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT. PMID:19707253

  3. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  4. Initial steps in anoxic testosterone degradation by Steroidobacter denitrificans.

    PubMed

    Chiang, Yin-Ru; Fang, Jia-You; Ismail, Wael; Wang, Po-Hsiang

    2010-07-01

    Steroid compounds have many important physiological activities in higher organisms. Testosterone and related steroids are important environmental contaminants that disrupt the endocrine systems of animals. The degradation of steroids, especially under anoxic conditions, is challenging because of their complex chemical structure. A denitrifying gamma-proteobacterium, Steroidobacter denitrificans, able to grow anaerobically on a variety of steroids as the sole carbon and energy source was adopted as a model organism to study the anoxic degradation of testosterone. We identified the initial intermediates involved in the anoxic testosterone degradation pathway of S. denitrificans. We demonstrated that under anoxic conditions, S. denitrificans initially oxidizes testosterone to 1-dehydrotestosterone, which is then transformed to androsta-1,4-diene-3,17-dione. In addition, it seems that androst-4-en-3,17-dione can also be directly produced from testosterone by S. denitrificans cells. In general, the initial steps of anoxic testosterone degradation by S. denitrificans are similar to those of the oxic pathway demonstrated in Comamonas testosteroni.

  5. Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage.

    PubMed

    Santosa, Sylvia; Bush, Nikki C; Jensen, Michael D

    2017-08-01

    Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. This was a prospective, randomized trial. Mayo Clinic Clinical Research Unit. Thirty-two male volunteers ages 18 to 50 participated in these studies. Volunteers were randomized to receive (1) no treatment (control), (2) injections (7.5 mg) of Lupron®, or (3) Lupron and testosterone (L+T) replacement for 49 days, resulting in 4 weeks of sex steroid suppression in the Lupron group. We measured body composition, fat cell size, adipose tissue meal FA and direct free FA storage, lipoprotein lipase (LPL), acyl coenzyme A synthetase (ACS), diacylglycerol acyltransferase activities, and CD36 content. Compared with control and L+T groups, acute testosterone deficiency resulted in greater femoral adipose tissue meal FA storage rates, fasting and fed LPL activity, and ACS activity. These results suggest that in men, testosterone plays a tonic role in restraining FA storage in femoral adipose tissue via suppression of LPL and ACS activities. FA storage mechanisms in men appear sensitive to short-term changes in testosterone concentrations.

  6. Plasmonic sensors for the competitive detection of testosterone.

    PubMed

    Yockell-Lelièvre, H; Bukar, N; McKeating, K S; Arnaud, M; Cosin, P; Guo, Y; Dupret-Carruel, J; Mougin, B; Masson, J-F

    2015-08-07

    The ability to detect small molecules in a rapid and sensitive manner is of great importance in the field of clinical chemistry, and the advancement of novel biosensors is key to realising point-of-care analysis for essential targets. Testosterone is an example of such a small molecule, the detection of which is important in both clinical analysis, and in the sporting industry to prevent doping. As such, a portable, rapid and sensitive test for testosterone would be of great use across a variety of analytical fields. Here we report on a novel method of testosterone analysis, based on a competitive inhibition assay utilising functionalized gold nanoparticles. Two sensing platforms are directly compared for the detection of testosterone based on both classical SPR and LSPR. We provide an in-depth discussion on the optimum surface chemistries needed to create a stable detection conjugate before successfully detecting testosterone using our newly developed portable 4-channel SPR instrument. We provide the first detailed study into the comparison of SPR and LSPR for the analysis of a small molecule, and provide a simple and effective method of testosterone detection that could potentially be extended to a variety of different analytes.

  7. Gonadotropin-induced testosterone response in peripubertal male alligators.

    PubMed

    Edwards, Thea M; Gunderson, Mark P; Milnes, Matthew R; Guillette, Louis J

    2004-02-01

    Based on the response to three different gonadotropin challenges, we evaluated seasonal production of testosterone in a group of captive-raised four-year-old male alligators that varied in size. To stimulate gonadal steroidogenesis, we injected each alligator with ovine FSH (150 ng/ml plasma). Plasma testosterone concentrations were measured in repeated blood samples taken between 0 and 72 h after FSH injection. To determine if there was seasonal variation in response, we repeated the experiment on the same alligators three times during the breeding season (March, May, and July, 2000). All alligators responded to exogenous FSH by exhibiting increased plasma concentrations of testosterone (p < 0.0001 for all months). However, the degree of the response depended on body size. Thus, larger alligators produced more testosterone and were more affected by changes in season compared to smaller alligators. We have previously observed that juvenile male alligators display seasonal changes in plasma testosterone concentrations that mimic the cycle observed in adult males. Our present data suggest that seasonal changes in plasma testosterone appear to be associated not only with changes in gonadotropin release but in gonadal responsiveness as well. We propose, given these observations, that alligators experience an extended period of puberty, during which the gonads synthesize gradually increasing steroid hormone concentrations. These peripubertal animals are not juveniles but sub-adults capable of responding to the seasonal signals associated with reproductive timing in adults.

  8. Replacement therapy: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine, testosterone and estrogen.

    PubMed

    Mitchell, D H; Owens, B

    1996-06-01

    Replacement therapy is routinely used to treat hormone deficiencies of patients who have had surgery or radiation therapy that damages the hypothalamus or pituitary gland. Hormones commonly replaced include: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine (T4), testosterone and estrogen. AVP, synthesized in the hypothalamus, is stored in and released by the posterior lobe of the pituitary gland. GH is synthesized and released by the anterior pituitary gland. The other hormones are produced and released by target glands each of which is stimulated by a specific anterior pituitary hormone, which in turn is controlled by release of a specific hypothalamic hormone. Feedback control by a high circulating concentration of the target gland's hormone regulates hypothalamic hormone release. Deficiency of AVP, important for water balance in the body, is restored with the synthetic analogue, 1-desamino-8-D-arginine vasopressin (DDAVP); it is given as a nasal spray or by injection. GH is required for normal growth in the developing child; recombinant GH, produced in bacteria, is injected subcutaneously. Adrenocorticotropic hormone (ACTH) controls release of cortisol which is produced by the adrenal cortex and enables the body to cope with stress; cortisol is replaced with prednisolone given orally. Thyroid stimulating hormone (TSH) controls release of the thyroid hormones, T4 and triiodothyronine (T3), which promote growth and development, and regulate energy metabolism; for replacement of T4, oral synthetic L-thyroxine is given. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control release of testosterone, which promotes maturation of sperm and development of male sexual characteristics; replacement testosterone is administered intramuscularly. In females, FSH and LH control release of estrogens and progesterone which prepare the reproductive tract for release of the ovum, fertilization, implantation and development of the embryo

  9. Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reperfusion Injury by Attenuating Mitochondrial Dysfunction in Testosterone-Deprived Rats

    PubMed Central

    Pongkan, Wanpitak; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2015-01-01

    Background Although testosterone deficiency is associated with increased risks of heart disease, the benefits of testosterone therapy are controversial. Moreover, current understanding on the cardiac effect of testosterone during cardiac ischemia-reperfusion (I/R) periods is unclear. We tested the hypothesis that testosterone replacement attenuates the impairment of left ventricular (LV) function and heart rate variability (HRV), and reduces the infarct size and arrhythmias caused by I/R injury in orchiectomized (ORX) rats. Methodology ORX or sham-operated male Wistar rats (n = 24) were randomly divided and received either testosterone (2 mg/kg, subcutaneously administered) or the vehicle for 8 weeks. The ejection fraction (EF) and HRV were determined at baseline and the 4th and 8th week. I/R was performed by left anterior descending coronary artery ligation for 30 minutes, followed by a 120-minute reperfusion. LV pressure, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. Results Prior to I/R, EF and HRV were impaired in the ORX group, but were restored in the testosterone-treated group. During I/R, arrhythmia scores and the infarct size were greater, and cardiac mitochondrial function was impaired, whereas the time to 1st VT/VF onset and the LV end-systolic pressure were decreased in the ORX group when compared to the sham group. Testosterone replacement attenuated the impairment of these parameters in ORX rats during I/R injury, but did not show any benefit or adverse effect in non-ORX rats. Conclusions Testosterone replacement restores cardiac function and autonomic regulation, and exerts cardioprotective effects during the I/R period via mitochondrial protection in ORX rats. PMID:25822979

  10. Effects of fetal testosterone on visuospatial ability.

    PubMed

    Auyeung, Bonnie; Knickmeyer, Rebecca; Ashwin, Emma; Taylor, Kevin; Hackett, Gerald; Baron-Cohen, Simon

    2012-06-01

    This study investigated whether fetal testosterone (FT) measured from second trimester amniotic fluid was related to specific aspects of visuospatial ability, in children aged 7-10 years (35 boys, 29 girls). A series of tasks were used: the children's Embedded Figures Test (EFT) (a test of attention to detail), a ball targeting task (measuring hand-eye coordination), and a computerized mental rotation task (measuring rotational ability). FT was a significant predictor for EFT scores in both boys and girls, with boys also showing a clear advantage for this task. No significant sex differences were observed in targeting. Boys scored higher than girls on mental rotation. However, no significant relationships were observed between FT and targeting or mental rotation. Girls' performance on the mental rotation and targeting tasks was significantly related to age, indicating that these tasks may have been too difficult for the younger children. These results indicate that FT has a significant role in some aspects of cognitive development but that further work is needed to understand its effect on the different aspects of visuospatial ability.

  11. Testosterone therapy, thrombosis, thrombophilia, cardiovascular events.

    PubMed

    Glueck, Charles J; Wang, Ping

    2014-08-01

    There are similar time intervals between starting testosterone therapy (TT) and development of thrombotic (~4.5 months) or cardiovascular (CVD) events (~3 months) which may, speculatively, reflect a shared pathophysiology. We have described thrombotic events 5 months (median) after starting TT in 38 men and 4 women, including 27 with deep venous thrombosis-pulmonary embolism, 12 with osteonecrosis, 1 with central retinal vein thrombosis, 1 with amaurosis fugax, and 1 with spinal cord infarction. In 8 men whose TT was continued, second thrombotic events occurred despite adequate anticoagulation with Coumadin in 8 men, 3 of whom had a third thrombotic event. Of these 42 cases, 40 had measures of thrombophilia-hypofibrinolysis, and 39 were found to have previously undiagnosed thrombophilia-hypofibrinolysis. Before beginning TT, especially in men with previous history of thrombotic events, we suggest that, at a minimum, measurements be made for the Factor V Leiden and Prothrombin mutations, Factors VIII and XI, and homocysteine, to identify men who should not receive TT. We need prospective data focused on whether there should be pre-TT screening based on history of previous venous thromboembolism or for all subjects for major gene thrombophilias. To better resolve questions about TT and all cause and cardiovascular morbidity and mortality and thrombosis, a long term, prospective, randomized, blinded study following the example of the Women's Health Initiative is needed. While we wait for prospective placebo-controlled TT outcome data, TT should be restricted to men with well-defined androgen deficiency syndromes.

  12. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease.

    PubMed

    Casaburi, Richard; Bhasin, Shalender; Cosentino, Louis; Porszasz, Janos; Somfay, Attila; Lewis, Michael I; Fournier, Mario; Storer, Thomas W

    2004-10-15

    Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). Men with COPD have high prevalence of low testosterone levels, which may contribute to muscle weakness. We determined effects of testosterone supplementation (100 mg of testosterone enanthate injected weekly) with or without resistance training (45 minutes three times weekly) on body composition and muscle function in 47 men with COPD (mean FEV(1) = 40% predicted) and low testosterone levels (mean = 320 ng/dl). Subjects were randomized to 10 weeks of placebo injections + no training, testosterone injections + no training, placebo injections + resistance training, or testosterone injections + resistance training. Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration (to the middle of the normal range for young men). The lean body mass (by dual-energy X-ray absorptiometry) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training (p < 0.001). Increase in one-repetition maximum leg press strength averaged 17.2% with testosterone alone, 17.4% with resistance training alone, and 26.8% with testosterone + resistance training (p < 0.001). Interventions were well tolerated with no abnormalities in safety measures. Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels.

  13. Testosterone Trajectories and Reference Ranges in a Large Longitudinal Sample of Male Adolescents

    PubMed Central

    Khairullah, Ammar; Cousino Klein, Laura; Ingle, Suzanne M.; May, Margaret T.; Whetzel, Courtney A.; Susman, Elizabeth J.; Paus, Tomáš

    2014-01-01

    Purpose Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development. Methods We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant’s testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years. Results The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty. Conclusions The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics. PMID:25268961

  14. The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males.

    PubMed

    Tikkanen, Roope; Saukkonen, Tero; Fex, Malin; Bennet, Hedvig; Rautiainen, Marja-Riitta; Paunio, Tiina; Koskinen, Mika; Panarsky, Rony; Bevilacqua, Laura; Sjöberg, Rickard L; Tiihonen, Jari; Virkkunen, Matti

    2016-10-01

    Herein, we examined insulin resistance (IR), insulin sensitivity (IS), beta cell activity, and glucose metabolism in subjects with antisocial personality disorder (ASPD), and whether the serotonin 2B (5-HT2B) receptor and testosterone have a role in energy metabolism. A cohort of subjects belonging to a founder population that included 98 ASPD males, aged 25-30, was divided into groups based on the presence of a heterozygous 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*; n = 9) or not (n = 89). Serum glucose and insulin levels were measured in a 5 h oral glucose tolerance test (75 g) and indices describing IR, IS, and beta cell activity were calculated. Body mass index (BMI) was also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were measured in cerebrospinal fluid, and testosterone levels from serum. An IR-like state comprising high IR, low IS, and high beta cell activity indices was observed among ASPD subjects without the HTR2B Q20* allele. By contrast, being an ASPD HTR2B Q20* carrier appeared to be preventive of these pathophysiologies. The HTR2B Q20* allele and testosterone predicted lower BMI independently, but an interaction between HTR2B Q20* and testosterone lead to increased insulin sensitivity among HTR2B Q20* carriers with low testosterone levels. The HTR2B Q20* allele also predicted reduced beta cell activity and enhanced glucose metabolism. Reduced 5-HT2B receptor function at low or normal testosterone levels may be protective of obesity. Results were observed among Finnish males having an antisocial personality disorder, which limits the generality. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.

    PubMed

    Gasco, M; Villegas, L; Yucra, S; Rubio, J; Gonzales, G F

    2007-08-01

    The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.

  16. Testosterone Conversion Blockade Increases Breathing Stability in Healthy Men during NREM Sleep

    PubMed Central

    Chowdhuri, Susmita; Bascom, Amy; Mohan, David; Diamond, Michael P.; Badr, M. Safwan

    2013-01-01

    Study Objectives: Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. Design: Randomization to oral finasteride vs. sham, single-center study. Setting: Sleep research laboratory. Participants: Fourteen healthy young males without sleep apnea Intervention: Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. Measurements and Results: The apnea threshold (AT) was defined as the end-tidal CO2 (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 between eupnea and AT. The apneic threshold and CO2 reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO2 reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. Conclusions: Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations. Citation: Chowdhuri S; Bascom A; Mohan D; Diamond MP; Badr MS. Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep. SLEEP 2013

  17. Testosterone influences spatial strategy preferences among adult male rats

    PubMed Central

    Spritzer, Mark D.; Fox, Elliott C.; Larsen, Gregory D.; Batson, Christopher G.; Wagner, Benjamin A.; Maher, Jack

    2013-01-01

    Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats’ strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent. PMID:23597827

  18. Time for international action on treating testosterone deficiency syndrome

    PubMed Central

    Carruthers, Malcolm

    2009-01-01

    Aim Testosterone deficiency is having an increasing impact on men's health because of global aging, higher levels of obesity, diabetes and metabolic syndrome and adverse environmental factors such as stress xenoestrogens and anti-androgens. The question addressed is to what extent the large body of evidence on the benefits and safety of testosterone therapy is applied in clinical practice. Methods Demographic data for men over the age of 50 from different regions of the world have been compared with the number of men in that age group estimated from sales figures to be receiving testosterone treatment. Results On the basis of estimate that 20% of men over 50 in the general population of each region could be expected to have testosterone deficiency symptoms, on average only these men (0.69%) in most European countries were receiving treatment. Proportion was higher in the UK (1.00%) and Germany (1.89%), but lower in France (0.49%), Italy (0.51%) and Russia (0.54%). Interestingly, Australia had higher figures (1.64%), in spite of tight state control measures on androgen use. The USA has the highest treatment rate (7.96%) and this is increasing rapidly. If the basis for the diagnosis was the more conventional combination of symptoms plus biochemical evidence of low total and free testosterone levels, androgen deficiency would be expected in at least 5% of men over 50, and percentage treatment rates therefore four times higher. However, even on that basis, only in the USA do these exceed 10%. Conclusions International action is urgently needed to raise awareness in the medical profession in the various countries of these remarkably low levels of testosterone treatment. Improvement in this requires education and motivation of doctors and those regulating the healthcare systems. A public awareness campaign is needed to educate men about the symptoms of testosterone deficiency and its impact on their health. PMID:19326293

  19. Predicting low testosterone in aging men: a systematic review

    PubMed Central

    Millar, Adam C.; Lau, Adrian N.C.; Tomlinson, George; Kraguljac, Alan; Simel, David L.; Detsky, Allan S.; Lipscombe, Lorraine L.

    2016-01-01

    Background: Physicians diagnose and treat suspected hypogonadism in older men by extrapolating from the defined clinical entity of hypogonadism found in younger men. We conducted a systematic review to estimate the accuracy of clinical symptoms and signs for predicting low testosterone among aging men. Methods: We searched the MEDLINE and Embase databases (January 1966 to July 2014) for studies that compared clinical features with a measurement of serum testosterone in men. Three of the authors independently reviewed articles for inclusion, assessed quality and extracted data. Results: Among 6053 articles identified, 40 met the inclusion criteria. The prevalence of low testosterone ranged between 2% and 77%. Threshold testosterone levels used for reference standards also varied substantially. The summary likelihood ratio associated with decreased libido was 1.6 (95% confidence interval [CI] 1.3–1.9), and the likelihood ratio for absence of this finding was 0.72 (95% CI 0.58–0.85). The likelihood ratio associated with the presence of erectile dysfunction was 1.5 (95% CI 1.3–1.8) and with absence of erectile dysfunction was 0.83 (95% CI 0.76–0.91). Of the multiple-item instruments, the ANDROTEST showed both the most favourable positive likelihood ratio (range 1.9–2.2) and the most favourable negative likelihood ratio (range 0.37–0.49). Interpretation: We found weak correlation between signs, symptoms and testosterone levels, uncertainty about what threshold testosterone levels should be considered low for aging men and wide variation in estimated prevalence of the condition. It is therefore difficult to extrapolate the method of diagnosing pathologic hypogonadism in younger men to clinical decisions regarding age-related testosterone decline in aging men. PMID:27325129

  20. Male rats secrete luteinizing hormone and testosterone episodically.

    PubMed

    Ellis, G B; Desjardins, C

    1982-05-01

    We studied the temporal aspects of endocrine signaling between the pituitary gland and testes by measuring moment to moment changes in blood LH and testosterone levels in individual male rats. Each rat was fitted with an indwelling vascular cannula, and blood was withdrawn every 5 min for 8-12 h. Rats were maintained throughout the intensive blood-sampling period with an isotonic blood replacement mixture containing rat red blood cells and a human plasma protein preparation. LH and testosterone measurements were made in plasma volumes of 50 and 60 microliters. Most rats released LH in well defined pulses, characterized by a rapid increase in plasma LH within 5-10 min and a gradual decline lasting for the next 50-70 min. LH pulses occurred singly or in trains of two to four. Episodes of testosterone secretion spanned 3-6 h and were marked by a slowly graded rise and fall of plasma testosterone. In several instances, testosterone episodes were preceded (1-2 h) by a train of closely coupled LH pulses. Within a particular animal on different days, hormone episodes varied in number, amplitude, and timing. A particular hormone profile did not serve as a reliable hormone signature for an individual rat. Many rats displayed a characteristic sequence of 1) multiple LH pulses, 2) a sustained testosterone episode, and 3) a period of no LH pulses. This tripartite sequence of events is viewed as the essence of pituitary-testicular stimulation, and testicular negative feedback. Intermittent, short term fluctuations in peripheral levels of LH and testosterone represent the blood-borne, gland to gland signals controlling hypothalamic-pituitary-testicular function in the normal rat.

  1. Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents.

    PubMed

    Arruzazabala, M L; Carbajal, D; Más, R; Molina, V; Rodríguez, E; González, V

    2004-01-01

    Benign prostatic hyperplasia (BPH) is the noncancerous, uncontrolled growth of prostate gland cells and stroma that can cause difficulty urinating. Fruit lipid extracts from saw palmetto, a palm from the Arecaceae family, are used for BPH management. The Cuban royal palm, Roystonea regia, is also a member of the Arecaceae family and therefore it was appropriate to investigate the protective effects of Roystonea regia fruit lipid extracts on prostatic hyperplasia. The aim of this study was to investigate whether D-004, a lipid extract from Roystonea regia fruits, prevented testosterone-induced PH in castrated and intact rodents. Two series of experiments were performed. The first one was conducted in castrated and intact rats, distributed into five groups of 10 rats per group. The negative control group was injected with soy oil and treated orally with vehicle, while the four testosterone-injected groups were treated with vehicle (positive control), D-004 100, 200 and 400 mg/kg, respectively. The other experiment was conducted in castrated and intact mice. These were distributed into four groups of 10 mice per group: a negative control group and three testosterone-injected groups, of which one was a positive control, while two received D-004 200 and 400 mg/kg, respectively. At study completion, the rodents were sacrificed and prostates removed and weighed. D-004 at doses of 100, 200 and 400 mg/kg significantly and dose-dependently prevented prostate enlargement in intact and castrated rats and mice. The percentage inhibitions obtained in mice were greater: 77% and 84% for intact and castrated mice, respectively. D-004 therapy did not affect body weight. It is concluded that D-004 administered orally significantly prevented testosterone-induced prostate enlargement in both intact and castrated rodents, indicating that an endogenous supply of testosterone is not necessary to observe such an effect The results of the present investigation support further studies of D

  2. Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study

    PubMed Central

    Traish, A M; Haider, A; Doros, G; Saad, F

    2014-01-01

    Aim The goal of this study was to determine if long-term testosterone (T) therapy in men with hypogonadism, henceforth referred to as testosterone deficiency (TD), ameliorates or improves metabolic syndrome (MetS) components. Methods We performed a cumulative registry study of 255 men, aged between 33 and 69 years (mean 58.02 ± 6.30) with subnormal plasma total T levels (mean: 9.93 ± 1.38; range: 5.89–12.13 nmol/l) as well as at least mild symptoms of TD assessed by the Aging Males' symptoms scale. All men received treatment with parenteral T undecanoate 1000 mg (Nebido®, Bayer Pharma, Berlin, Germany), administered at baseline and 6 weeks and thereafter every 12 weeks for up to 60 months. Lipids, glucose, liver enzymes and haemoglobin A1c analyses were carried out in a commercial laboratory. Anthropometric measurements were also made throughout the study period. Results Testosterone therapy restored physiological T levels and resulted in reductions in total cholesterol (TC) [7.29 ± 1.03 to 4.87 ± 0.29 mmol/l (281.58 ± 39.8 to 188.12 ± 11.31 mg/dl)], low-density lipoprotein cholesterol [4.24 ± 1.07 to 2.84 ± 0.92 mmol/l (163.79 ± 41.44 to 109.84 ± 35.41 mg/dl)], triglycerides [3.14 ± 0.58 to 2.16 ± 0.13 mmol/l (276.16 ± 51.32 to 189.78 ± 11.33 mg/dl)] and increased high-density lipoprotein levels [1.45 ± 0.46 to 1.52 ± 0.45 mmol/l (56.17 ± 17.79 to 58.85 ± 17.51 mg/dl)] (p < 0.0001 for all). There were marked reductions in systolic and diastolic blood pressure, blood glucose, haemoglobin A1c, C-reactive protein (6.29 ± 7.96 to 1.03 ± 1.87 U/l), alanine aminotransferase and aspartate aminotransferase (p < 0.0001 for all). Conclusions Long-term T therapy, at physiological levels, ameliorates MetS components. These findings strongly suggest that T therapy in hypogonadal men may prove useful in reducing the risk of cardiometabolic diseases. PMID:24127736

  3. Blood donation and testosterone replacement therapy.

    PubMed

    Chin-Yee, Benjamin; Lazo-Langner, Alejandro; Butler-Foster, Terrie; Hsia, Cyrus; Chin-Yee, Ian

    2017-03-01

    Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT. We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be on TRT. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors. We identified 39 patients on TRT who presented for blood donation over a 2-year period. The mean hemoglobin level at all clinic visits was 173 g/L (range, 134-205 g/L; n = 108). Hemoglobin concentrations of 180 g/L or more (calculated hematocrit, ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations. Hemoglobin concentrations were elevated in donors on TRT, and significant numbers had hemoglobin levels above those recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain a hematocrit below 54%. Our findings raise concerns about the persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has reduced or eliminated the risks of TRT-induced polycythemia. © 2017 AABB.

  4. FATHERHOOD, PAIRBONDING AND TESTOSTERONE IN THE PHILIPPINES

    PubMed Central

    Kuzawa, Christopher W.; Gettler, Lee; Muller, Martin N.; McDade, Thomas W.; Feranil, Alan B.

    2009-01-01

    In species with a high level of paternal care, including humans, testosterone (T) is believed to help mediate the trade-off between parenting and mating effort. This hypothesis is supported by the observation of lower T in pairbonded men or fathers compared to single, non-fathers; however, prior work has highlighted population variation in the association between T and pairbonding or fatherhood status. Here we evaluate this hypothesis in a large (n=890), representative birth cohort of young men (age range 20.5–22.5 years) living in Cebu City, the Philippines. Bioavailable T was measured in saliva collected prior to bed and immediately upon waking the following morning. Plasma T and luteinizing hormone (LH) were measured in morning plasma samples. In this sample, 20% of men were pairbonded, defined as living with a partner or married, 13% were fathers, and roughly half of fathers reported involvement in childcare. Pairbonded men had significantly lower T at both times of day. Unlike in other populations, this relationship was accounted for entirely by fatherhood status: among the large sub-sample of non-fathers, mean T was nearly identical among pairbonded and single men. There was a strong association between self-reported involvement in childcare and lower evening T, supporting the idea that the evening nadir in T is related to social interactions across the day. Similar relationships were found for total plasma T and LH, suggesting that these relationships are coordinated by centrally-mediated changes in LH secretion. The relatively modest T difference in relation to fatherhood at Cebu, in comparison to other studies, may reflect a lower level of paternal involvement in childcare activities in this population. Our findings using a large, well-characterized birth cohort support the hypothesized role of T as mediator of mating and parenting effort in humans, while contributing evidence for cultural variation in the relative importance of pairbonding and fathering

  5. Recent topics related to testosterone deficiency syndrome in Japan

    PubMed Central

    Tsujimura, Akira; Nonomura, Norio

    2011-01-01

    Androgens, the levels of which decrease with ageing, play many physiological roles in various organs. Testosterone deficiency syndrome (TDS) has received widespread attention in the last several years. First-line treatment for TDS should be testosterone replacement therapy (TRT), which is reported to improve several TDS symptoms. Recently, a clinical practice manual for TDS was written and published by a collaborative team from the Japanese Urological Association and the Japanese Society for the Study of the Aging Male to recommend standard procedures for the diagnosis, treatment, prevention and monitoring of adverse reactions to TRT and for post-treatment assessment. In this manual, intramuscular injection of testosterone enanthate or human chorionic gonadotropin and the testosterone gel ‘Glowmin' were recommended as TRT. Currently, two topics related to TDS are being focused on in Japan: the relationship between TDS and metabolic syndrome and treatment options for eugonadal patients with TDS symptoms. In this review, the possibility of TRT for metabolic syndrome as well as the relationship between testosterone and adiponectin, which is a key molecule in metabolic syndrome, is discussed. Finally, the possibility of herbal medicines as a treatment option for patients with TDS is addressed, especially for eugonadal patients, because eugonadal men with TDS symptoms account for approximately 30% of the general population. The increase in the levels of several cytokines, such as IL-8, IL-13, interferon-γ and tumor necrosis factor-α, after herbal medicine treatment may be the reason for this efficacy. PMID:21460860

  6. Testosterone regulates metabolism of plasma chylomicrons in rats

    SciTech Connect

    Staprans, I.; Rapp, J.H.; Pan, X.M.; Ong, D.L.; Feingold, K.R. )

    1990-07-01

    Previously we demonstrated a marked sex difference in the metabolism of chylomicrons in adult rats. In males, radiolabeled chylomicrons displayed a longer dwell time on endothelial surfaces, which resulted in a decreased chylomicron uptake by the liver. The increased rate of chylomicron metabolism in females was associated with increased postheparin lipoprotein lipase activity. In the present study, we have investigated the effects of physiological doses of sex steroid hormones on the metabolism of chylomicrons and postheparin lipoprotein lipase activity. No sex differences were found in prepubertal animals. We also found no difference in chylomicron metabolism in control female, castrated female, estrogen-treated female, castrated male, and estrogen-treated male rats. However, control male, testosterone-treated male, and testosterone-treated female rats showed increased endothelial binding of chylomicrons and decreased chylomicron uptake by the liver. Postheparin lipoprotein lipase activity also was decreased by testosterone administration. In parallel with the alterations in chylomicron metabolism, serum high density lipoprotein levels in male rats decreased with testosterone administration. These results indicate that the differences in chylomicron metabolism, postheparin lipoprotein lipase activities, and serum high density lipoprotein levels observed between male and female rats are due to testosterone.

  7. Hypothalamic control of the male neonatal testosterone surge.

    PubMed

    Clarkson, Jenny; Herbison, Allan E

    2016-02-19

    Sex differences in brain neuroanatomy and neurophysiology underpin considerable physiological and behavioural differences between females and males. Sexual differentiation of the brain is regulated by testosterone secreted by the testes predominantly during embryogenesis in humans and the neonatal period in rodents. Despite huge advances in understanding how testosterone, and its metabolite oestradiol, sexually differentiate the brain, little is known about the mechanism that actually generates the male-specific neonatal testosterone surge. This review examines the evidence for the role of the hypothalamus, and particularly the gonadotropin-releasing hormone (GnRH) neurons, in generating the neonatal testosterone surge in rodents and primates. Kisspeptin-GPR54 signalling is well established as a potent and critical regulator of GnRH neuron activity during puberty and adulthood, and we argue here for an equally important role at birth in driving the male-specific neonatal testosterone surge in rodents. The presence of a male-specific population of preoptic area kisspeptin neurons that appear transiently in the perinatal period provide one possible source of kisspeptin drive to neonatal GnRH neurons in the mouse.

  8. Testosterone-secreting adrenal adenoma in a peripubertal girl

    SciTech Connect

    Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

    1987-11-13

    A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.

  9. Testosterone, cortisol and anxiety in elite field hockey players.

    PubMed

    Aguilar, Raúl; Jiménez, Manuel; Alvero-Cruz, José R

    2013-07-02

    The aim of the present study was to assess the change in the levels of testosterone and cortisol after victory and defeat in male field hockey players during an important tournament. In the beginning of the game series, the players were ranked very closely to achieve (for the first time) the championship rising to The Honor Division-A, the highest status national category. The first game resulted in a 7-4 victory, the second game resulted in a 6-1 victory, and the third game resulted in a 1-2 defeat. As expected, there were changes in testosterone levels after the competition, dropping in the game which ended in defeat, and rising slightly in the two games which ended in victory; there were also changes in cortisol levels, rising in the game which ended in defeat, and showing no variations in the games which ended in victory; correlational analyses congruently showed that defeat led to rises in cortisol whereas victory led to rises in testosterone; anticipatory somatic anxiety was related to cortisol levels prior to games, and physical exertion during competition was related to the change in testosterone levels (suggesting an inhibitory effect) but not to the change in cortisol levels. Hence, this pattern of hormonal responses to a real-life dominance challenge complied with Mazur's (1985) [16] biosocial model of status and dominance motivation, by showing that testosterone and cortisol are linked to victory and defeat in a theoretically predictable fashion.

  10. Effect of testosterone therapy on the female voice

    PubMed Central

    Glaser, R.; York, A.; Dimitrakakis, C.

    2016-01-01

    Abstract Objectives This prospective study was designed to investigate the effect of testosterone, delivered by subcutaneous implants, on the female voice. Methods Ten women who had opted for testosterone therapy were recruited for voice analysis. Voices were recorded prior to treatment and at 3 months, 6 months, and 12 months while on testosterone therapy. Acoustic samples were collected with subjects reading a sentence, reading a paragraph, and participating in a conversation. Significant changes in the voice over time were investigated using a repeated-measures analysis of variance with the fundamental frequency (F 0) as a response variable. Demographic variables associated with characteristics of the voice were assessed. Results There were no significant differences in average F 0 related to smoking history, menopausal status, weight, or body mass index. There was no difference in average fundamental speaking frequency (sentence, paragraph, conversation) between the pre-treatment group and any post-treatment group at 3 and 12 months. There was an increase in sentence speech F 0 at 6 months. Two of three patients with lower than expected F 0 at baseline improved on testosterone therapy. Conclusion Therapeutic levels of testosterone, delivered by subcutaneous implant, had no adverse affect on the female voice including lowering or deepening of the voice. PMID:26857354

  11. Natural selection on testosterone production in a wild songbird population.

    PubMed

    McGlothlin, Joel W; Whittaker, Danielle J; Schrock, Sara E; Gerlach, Nicole M; Jawor, Jodie M; Snajdr, Eric A; Ketterson, Ellen D

    2010-06-01

    Because of their role in mediating life-history trade-offs, hormones are expected to be strongly associated with components of fitness; however, few studies have examined how natural selection acts on hormonal variation in the wild. In a songbird, the dark-eyed junco (Junco hyemalis), field experiments have shown that exogenous testosterone alters individuals' resolution of the survival-reproduction trade-off, enhancing reproduction at the expense of survival. Here we used standardized injections of gonadotropin-releasing hormone (GnRH) to assay variation in the testosterone production of males. Using measurements of annual survival and reproduction, we found evidence of strong natural selection acting on GnRH-induced increases in testosterone. Opposite to what would be predicted from the survival-reproduction trade-off, patterns of selection via survival and reproduction were remarkably similar. Males with GnRH-induced testosterone production levels that were slightly above the population mean were more likely to survive and also produced more offspring, leading to strong stabilizing selection. Partitioning reproduction into separate components revealed positive directional selection via within-pair siring success and stabilizing selection via extrapair mating success. Our data represent the most complete demonstration of natural selection on hormones via multiple fitness components, and they complement previous experiments to illuminate testosterone's role in the evolution of life-history trade-offs.

  12. Testosterone and paternal care in East African foragers and pastoralists.

    PubMed

    Muller, Martin N; Marlowe, Frank W; Bugumba, Revocatus; Ellison, Peter T

    2009-01-22

    The 'challenge hypothesis' posits that testosterone facilitates reproductive effort (investment in male-male competition and mate-seeking) at the expense of parenting effort (investment in offspring and mates). Multiple studies, primarily in North America, have shown that men in committed relationships, fathers, or both maintain lower levels of testosterone than unpaired men. Data from non-western populations, however, show inconsistent results. We hypothesized that much of this cross-cultural variation can be attributed to differential investment in mating versus parenting effort, even among married fathers. Here, we directly test this idea by comparing two neighbouring Tanzanian groups that exhibit divergent styles of paternal involvement: Hadza foragers and Datoga pastoralists. We predicted that high levels of paternal care by Hadza fathers would be associated with decreased testosterone in comparison with non-fathers, and that no such difference between fathers and non-fathers would be evident in Datoga men, who provide minimal direct paternal care. Twenty-seven Hadza men and 80 Datoga men between the ages of 17 and 60 provided morning and afternoon saliva samples from which testosterone was assayed. Measurements in both populations confirmed these predictions, adding further support to the hypothesis that paternal care is associated with decreased testosterone production in men.

  13. Hypothalamic control of the male neonatal testosterone surge

    PubMed Central

    Clarkson, Jenny; Herbison, Allan E.

    2016-01-01

    Sex differences in brain neuroanatomy and neurophysiology underpin considerable physiological and behavioural differences between females and males. Sexual differentiation of the brain is regulated by testosterone secreted by the testes predominantly during embryogenesis in humans and the neonatal period in rodents. Despite huge advances in understanding how testosterone, and its metabolite oestradiol, sexually differentiate the brain, little is known about the mechanism that actually generates the male-specific neonatal testosterone surge. This review examines the evidence for the role of the hypothalamus, and particularly the gonadotropin-releasing hormone (GnRH) neurons, in generating the neonatal testosterone surge in rodents and primates. Kisspeptin–GPR54 signalling is well established as a potent and critical regulator of GnRH neuron activity during puberty and adulthood, and we argue here for an equally important role at birth in driving the male-specific neonatal testosterone surge in rodents. The presence of a male-specific population of preoptic area kisspeptin neurons that appear transiently in the perinatal period provide one possible source of kisspeptin drive to neonatal GnRH neurons in the mouse. PMID:26833836

  14. [Testosterone deficit syndrome in fertile or subfertile men].

    PubMed

    Cruz-Navarro, Nicolas

    2013-09-01

    Spermatogenesis is a well defined, complex,long and very orderlyprocess of cellular division and differentiation that is under regulation by endocrine signals (GnRH, LH, Inhibin and FSH ): paracrine signals, derived from the interrelation of the various types of cells in the tubules and interstitium (even in a juxtacrine way), and autocrine signals of self communication of the cell with itself. Testosterone plays an essential role in this process. In the testicular tubules, testosterone reaches concentrations 100 times higher than circulating testosterone in the blood stream. From a reproduction point of view, we can find two completely different scenarios in relation to testosterone deficit syndrome with a similar final clinical result: The difficulties of the male to have children. On one side the presence of hypogonadism, which requires a different management depending of the clinical priority and wishes of parenthood of the patient an his partner. On the other side, the opposite situation, the patient who requires or is already under testosterone therapy. In patients with hypogonadotropic hypogonadism, when patient's clinical priority is fertility, the treatment to restore normal spermatogenesis requires external administration of gonadotropins. Treatment must be prolonged, at least 12-18 months. 95% of the cases will have a favorable response, meaning the finding of spermatozoids in ejaculation sperm as a consequence of spermatogenesis restoration.

  15. Single dose testosterone administration reduces loss chasing in healthy females.

    PubMed

    Wu, Yin; Liu, Jinting; Qu, Lujing; Eisenegger, Christoph; Clark, Luke; Zhou, Xiaolin

    2016-09-01

    Testosterone has been linked to modulation of impulsivity and risky choice, potentially mediated by changes in reward or punishment sensitivity. This study investigated the effect of testosterone on risk-taking and the adjustment of risk-taking on trials following a gain or a loss. Loss chasing is operationalized herein as the propensity to recover losses by increasing risky choice. Healthy female participants (n=26) received a single-dose of 0.5mg sublingual testosterone in a double-blind, placebo-controlled crossover design. At 240min post-administration, participants performed a gambling task with a high and a low risk option. In the placebo condition, participants were more likely to choose the high risk option following losses compared to wins. This effect was abolished on the testosterone session. Ignoring prior outcomes, no overall changes in risk-taking were observed. Our data indicate that testosterone affects human decision-making via diminishing sensitivity to punishment. Copyright © 2016. Published by Elsevier Ltd.

  16. Effects of Testosterone Administration on Strategic Gambling in Poker Play.

    PubMed

    van Honk, Jack; Will, Geert-Jan; Terburg, David; Raub, Werner; Eisenegger, Christoph; Buskens, Vincent

    2016-01-04

    Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone's primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players' bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one's reputation by revealing deceptive intent, and secondly, not calling the other players' bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous.

  17. Safety and efficacy of testosterone gel in the treatment of male hypogonadism

    PubMed Central

    Lakshman, Kishore M; Basaria, Shehzad

    2009-01-01

    Transdermal testosterone gels were first introduced in the US in 2000. Since then, they have emerged as a favorable mode of testosterone substitution. Serum testosterone levels reach a steady-state in the first 24 hours of application and remain in the normal range for the duration of the application. This pharmacokinetic profile is comparable to that of testosterone patch but superior to injectable testosterone esters that are associated with peaks and troughs with each dose. Testosterone gels are as efficacious as patches and injectable forms in their effects on sexual function and mood. Anticipated increases in prostate-specific antigen with testosterone therapy are not significantly different with testosterone gels, and the risk of polycythemia is lower than injectable modalities. Application site reactions, a major drawback of testosterone patches, occur less frequently with testosterone gels. However, inter-personal transfer is a concern if appropriate precautions are not taken. Superior tolerability and dose flexibility make testosterone gel highly desirable over other modalities of testosterone replacement. Androgel and Testim, the two currently available testosterone gel products in the US, have certain brand-specific properties that clinicians may consider prior to prescribing. PMID:19966909

  18. Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells

    PubMed Central

    Hwang, Thomas IS; Liao, Tien-Ling; Lin, Ji-Fan; Lin, Yi-Chia; Lee, Shu-Yu; Lai, Yen-Chun; Kao, Shu-Huei

    2011-01-01

    Testosterone replacement therapy has benefits for aging men and those with hypogonadism. However, the effects of exogenous testosterone on Leydig cells are still unclear and need to be clarified. In this report, we demonstrate that testosterone supplementation can reduce oxidative damage in Leydig cells. The TM3 Leydig cell line was used as an in vitro cell model in this study. Cytoprotective effects were identified with 100-nmol l−1 testosterone treatment, but cytotoxic effects were found with ≥500-nmol l−1 testosterone supplementation. Significantly reduced reactive oxygen species (ROS) generation, lipid peroxide contents and hypoxia induction factor (HIF)-1α stabilization and activation were found with 100-nmol l−1 testosterone treatment. There was a 1.72-fold increase in ROS generation in the 500-nmol l−1 compared to the 100-nmol l−1 testosterone treatment. A 1.58-fold increase in steroidogenic acute regulatory protein (StAR) expression was found in 50-nmol l−1 testosterone-treated cells (P<0.01). Chemically induced hypoxia was attenuated by testosterone supplementation. Leydig cells treated with low-dose testosterone supplementation showed cytoprotection by decreasing ROS and lipid peroxides, increasing StAR expression and relieving hypoxia stress as demonstrated by HIF-1α stabilization. Increased oxidative damage was found with ≥500-nmol l−1 testosterone manipulation. The mechanism governing the differential dose effects of testosterone on Leydig cells needs further investigation in order to shed light on testosterone replacement therapy. PMID:21297653

  19. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  20. Increase of the transdermal penetration of testosterone by miconazole nitrate.

    PubMed

    Baert, Bram; Roche, Nathalie; Burvenich, Christian; De Spiegeleer, Bart

    2012-12-01

    Miconazole nitrate is an imidazole derivative used to treat skin disorders caused by fungi. The aim of this study was to investigate in a systematic way whether miconazole nitrate can have skin penetration enhancing properties. Using Franz diffusion cells, three representative model compounds (caffeine, testosterone and ibuprofen) were applied to human skin as 10 mM aqueous-ethanolic solutions with or without 1 mM of miconazole nitrate. The apparent permeability coefficient K(p) for each of the model compounds was determined with and without miconazole nitrate. While a statistically significant penetration enhancement effect of 33% was found for testosterone, no overall statistically significant effect could be demonstrated for caffeine and ibuprofen. The increase in skin permeability of testosterone is mainly due to an improved partitioning from the dose solution into the skin, thereby resulting in a higher delivery through the human skin. Our results indicate that miconazole can act as a penetration enhancer.

  1. Testosterone biotransformation by the isolated perfused canine pancreas

    SciTech Connect

    Fernandez-del Castillo, C.; Diaz-Sanchez, V.; Varela-Fascinetto, G.; Altamirano, A.; Odor-Morales, A.; Lopez-Medrano, R.M.; Robles-Diaz, G. )

    1991-01-01

    There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, (3H)testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5 alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with (3H)testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p less than 0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis.

  2. Responsiveness to testosterone of male gerbils from known intrauterine positions.

    PubMed

    Clark, M M; Bishop, A M; vom Saal, F S; Galef, B G

    1993-06-01

    Following either a) castration or b) both castration and implantation with capsules releasing a constant, physiological dose of testosterone, adult male Mongolian gerbils that had matured in intrauterine positions between two male fetuses still scent marked with greater frequency than did male gerbils that had matured in intrauterine positions between two female fetuses. We also found significant positive correlations between the relative frequency of scent marking exhibited by individual male gerbils when intact, after castration and after both castration and implantation with capsules releasing testosterone. Each of these findings is consistent with the view that differential exposure to testosterone, as a consequence of fetal intrauterine position, has lasting effects on the organization of scent-marking by male gerbils.

  3. Changes in saliva testosterone after psychological stimulation in men.

    PubMed

    Hellhammer, D H; Hubert, W; Schürmeyer, T

    1985-01-01

    Saliva testosterone (ST) concentration was measured in 20 young adult and healthy men before, during and after the presentation of five different films. The films were selected to provoke erotic, sexual, aggressive, stressful and neutral stimulation, respectively. An increase in ST was found 15 min after the onset of both the erotic and the sexual stimulation, while a decline of ST levels was observed during the stressful movie showing dental surgery. No changes were found for either the neutral or the aggressive stimulant. Furthermore, no differences were found between ST levels before and after the showing of any of the films. Thus, saliva testosterone responds quickly to psychological stimulation, and may provide a practical alternative to testosterone measurements in serum under psychological test situations.

  4. The role of testosterone in trichloroethylene penetration in vitro

    SciTech Connect

    McCormick, K.; Abdel-Rahman, M.S. )

    1991-02-01

    Sex differences are known to exist in the metabolism and bioavailability of trichloroethylene (TCE). This study revealed that dermal penetration of ({sup 14}C)TCE in vitro was twofold greater in untreated female than in untreated male Sprague-Dawley rats. Since testosterone has been shown to mediate a wide variety of sex differences, its role in dermal penetration of ({sup 14}C)TCE was investigated. Penetration was measured by using an in vitro evaporation-penetration cell with a 10-hour collection period. Depriving male rats of testosterone (by castration) resulted in increased values for total penetration, area under the curve (AUC), and penetration slopes compared to those found in the female control group. Administration of testosterone to female animals produced values for total penetration, AUC, and penetration slopes significantly lower than those of the female control group.

  5. Partial Androgen Deficiency, Depression, and Testosterone Supplementation in Aging Men

    PubMed Central

    Amore, Mario; Innamorati, Marco; Costi, Sara; Sher, Leo; Girardi, Paolo; Pompili, Maurizio

    2012-01-01

    The aim of this review was to summarize current knowledge on the correlation between depressive symptoms with a syndrome called partial androgen deficiency of the aging male (PADAM) and on the potential benefits of testosterone (T) treatment on mood. Despite, the causative nature of the relationship between low T levels and depression is uncertain, many hypogonadal men suffer from depression and vice versa several depressed patients are affected by hypogonadism. Supplementation with testosterone failed to show sound evidence of effectiveness in the treatment of depression. Nevertheless, testosterone supplementation has proved to be effective on some domains significant for the quality of life of aged patients with PADAM (sexual function and cognitive functions, muscular strengths). PMID:22719760

  6. Effects of aromatase inhibition vs. testosterone in older men with low testosterone: randomized-controlled trial.

    PubMed

    Dias, J P; Melvin, D; Simonsick, E M; Carlson, O; Shardell, M D; Ferrucci, L; Chia, C W; Basaria, S; Egan, J M

    2016-01-01

    Aging in men is associated with loss of bone mass, impaired physical function and altered body composition. The objective of this proof-of-concept randomized, double-blind, placebo-controlled, parallel-group, single-center trial was to determine the relative effects of testosterone (T) and estradiol (E(2)) on bone mineral density, body composition, and physical performance in older men. The primary outcome was lumbar spine bone mineral density (BMD), and secondary outcomes were body composition, muscle strength, gait speed, and sex hormone concentrations. Forty three men (age range, 65-82 years; mean age 71 years) with low total T levels <350 ng/dL were randomized to one of three groups: 5 g transdermal testosterone gel (TT) (N = 16), anastrozole (AI) 1 mg (N = 14) or placebo daily (N = 13) for 12 months. Outcomes were assessed at baseline, 3, 6, and 12 months. Both TT and AI increased serum TT levels (>500 ng/dL, p < 0.05) compared to baseline; T values remained stable throughout the duration of the trial. At 12 months, TT improved the primary outcome of lumbar spine BMD (p < 0.01).Both interventions improved knee strength at 12 months compared to baseline (p < 0.05) while lean body mass significantly increased only in the AI group at 6 and 12 months (1.49 ± 0.38 kg, p < 0.01; 1.24 ± 0.39 kg, p < 0.05, respectively) compared to baseline. Interestingly, TT improved fast gait speed at 3 and 12 months (p < 0.01, p < 0.05, respectively). In summary, this proof-of-concept study confirms that aromatization of T is required for maintaining BMD in older men with low-T levels. The trial also uncovered the novel finding that aromatization of T is required for improvement in fast gait speed, an observation that needs to be verified in future studies.

  7. Injection of testosterone may be safer and more effective than transdermal administration for combating loss of muscle and bone in older men.

    PubMed

    Borst, Stephen E; Yarrow, Joshua F

    2015-06-15

    The value of testosterone replacement therapy (TRT) for older men is currently a topic of intense debate. While US testosterone prescriptions have tripled in the past decade (9), debate continues over the risks and benefits of TRT. TRT is currently prescribed for older men with either low serum testosterone (T) or low T plus accompanying symptoms of hypogonadism. The normal range for serum testosterone is 300 to 1,000 ng/dl. Serum T ≤ 300 ng/dl is considered to be low, and T ≤ 250 is considered to be frank hypogonadism. Most experts support TRT for older men with frank hypogonadism and symptoms. Treatment for men who simply have low T remains somewhat controversial. TRT is most frequently administered by intramuscular (im) injection of long-acting T esters or transdermally via patch or gel preparations and infrequently via oral administration. TRT produces a number of established benefits in hypogonadal men, including increased muscle mass and strength, decreased fat mass, increased bone mineral density, and improved sexual function, and in some cases those benefits are dose dependent. For example, doses of TRT administered by im injection are typically higher than those administered transdermally, which results in greater musculoskeletal benefits. TRT also produces known risks including development of polycythemia (Hct > 50) in 6% of those treated, decrease in HDL, breast tenderness and enlargement, prostate enlargement, increases in serum PSA, and prostate-related events and may cause suppression of the hypothalamic-pituitary-gonadal axis. Importantly, TRT does not increase the risk of prostate cancer. Putative risks include edema and worsening of sleep apnea. Several recent reports have also indicated that TRT may produce cardiovascular (CV) risks, while others report no risk or even benefit. To address the potential CV risks of TRT, we have recently reported via meta-analysis that oral TRT increases CV risk and suggested that the CV risk profile for im TRT

  8. Transdermal testosterone delivery: comparison between scrotal and nonscrotal delivery systems.

    PubMed

    Lin, S; Xing, Q F; Chien, Y W

    1999-08-01

    The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs). Testoderm, designed to deliver testosterone through scrotal skin, and Androderm, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is approximately 13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration-time curve (AUC0-28)[665 versus 3208 (ng/dl) x hr] between these T-TDSs. However, there is no difference in time to reach Cmax mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (approximately 13-fold) between the nonscrotal and scrotal T-TDSs.

  9. Irisin and Testosterone in Men with Metabolic Syndrome.

    PubMed

    Kamenov, Zdravko; Assyov, Yavor; Angelova, Petya; Gateva, Antoaneta; Tsakova, Adelina

    2017-07-31

    The beneficial effects of testosterone on the metabolism and body composition of men are well established but the exact mechanisms of these effects are not clearly understood. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". One such myokine, irisin, has been shown to also have potential beneficial metabolic effects. The aim of this pilot study was to evaluate the association of serum testosterone with circulating serum irisin levels in men with metabolic syndrome. A total 128 men with metabolic syndrome (MS) based on the IDF criteria participated in the study. Irisin serum concentration was determined by means of ELISA. Mean age±SD of the study participants was 51.8±8.3 years. Seventy percent of the subjects had type 2 diabetes mellitus. Circulating irisin was inversely associated with serum testosterone (r=-0.279, p<0.01) and was significantly higher in subjects with hypogonadism - mean±SD 252.0±147.1 vs.172.9±92.2 ng/ml (p=0.002). ROC analysis of serum irisin value was determined for distinguishing subjects with hypogonadism (AUC=0.670). In a multiple linear regression model with BMI, FPG, age, and irisin, only BMI (β=-0.228, p=0.004) and irisin (β=-0.170, p=0.045) were variables independently associated with testosterone concentrations. Irisin is negatively associated with serum testosterone in our population sample of men with MS. This might suggest a possible involvement of myokines and testosterone with regards to the human metabolism. As no such data on this association has been reported in the literature thus far, further prospective studies are required to elucidate this correlation. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production

    EPA Science Inventory

    Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have...

  11. Modulation of pain sensation by stress-related testosterone and cortisol.

    PubMed

    Choi, J C; Chung, M I; Lee, Y D

    2012-10-01

    Stress increases cortisol and decreases testosterone. It is not known whether pain is affected by stress-related testosterone. Therefore, we investigated whether stress can affect pain perception by decreasing testosterone and increasing cortisol. Pain thresholds, pain and anxiety ratings and salivary testosterone and cortisol levels were measured in 46 healthy men during resting and stressful conditions. Pain was induced by electrical stimulation. Stress was induced by having participants perform a medical test. Stress significantly increased anxiety ratings and salivary cortisol levels, but decreased salivary testosterone levels. Stress also increased pain ratings and decreased pain thresholds. During stress, cortisol levels were negatively correlated with pain thresholds and testosterone levels were positively correlated with pain thresholds. Results indicated that testosterone can decrease and cortisol can increase pain induced by electrical stimulation, suggesting that acute clinical pain may be relieved by controlling stress and managing consequent stress-related testosterone and cortisol.

  12. Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production

    EPA Science Inventory

    Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have...

  13. A comparison of salivary testosterone measurement using immunoassays and tandem mass spectrometry.

    PubMed

    Welker, Keith M; Lassetter, Bethany; Brandes, Cassandra M; Prasad, Smrithi; Koop, Dennis R; Mehta, Pranjal H

    2016-09-01

    Enzyme immunoassays (EIAs) are widely used to measure salivary testosterone. However, little is known about how accurately different EIAs assess testosterone, partially because estimates across various EIAs differ considerably. We compared testosterone concentrations across EIAs of three commonly used manufacturers (DRG International, Salimetrics, and IBL International) to liquid chromatography tandem mass spectrometry (LC-MS/MS). Relative to EIAs from Salimetrics and IBL International, EIAs supplied by DRG International provided the closest approximation to LC-MS/MS testosterone concentrations, followed closely by EIAs from Salimetrics, and then IBL. Additionally, EIAs tended to inflate estimates of lower testosterone concentrations in women. Examining our results and comparing them to existing data revealed that testosterone EIAs had decreased linear correspondence with LC-MS/MS in comparison to cortisol EIAs. Overall, this paper provides researchers with information to better measure testosterone in their research and more accurately compare testosterone measurements across different methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Testosterone Stimulates Duox1 Activity through GPRC6A in Skin Keratinocytes*

    PubMed Central

    Ko, Eunbi; Choi, Hyun; Kim, Borim; Kim, Minsun; Park, Kkot-Nara; Bae, Il-Hong; Sung, Young Kwan; Lee, Tae Ryong; Shin, Dong Wook; Bae, Yun Soo

    2014-01-01

    Testosterone is an endocrine hormone with functions in reproductive organs, anabolic events, and skin homeostasis. We report here that GPRC6A serves as a sensor and mediator of the rapid action of testosterone in epidermal keratinocytes. The silencing of GPRC6A inhibited testosterone-induced intracellular calcium ([Ca2+]i) mobilization and H2O2 generation. These results indicated that a testosterone-GPRC6A complex is required for activation of Gq protein, IP3 generation, and [Ca2+]i mobilization, leading to Duox1 activation. H2O2 generation by testosterone stimulated the apoptosis of keratinocytes through the activation of caspase-3. The application of testosterone into three-dimensional skin equivalents increased the apoptosis of keratinocytes between the granular and stratified corneum layers. These results support an understanding of the molecular mechanism of testosterone-dependent apoptosis in which testosterone stimulates H2O2 generation through the activation of Duox1. PMID:25164816

  15. Herpes - oral

    MedlinePlus

    Cold sore; Fever blister; Oral herpes simplex; Herpes labialis; Herpes simplex ... Oral herpes is a common infection of the mouth area. It is caused by ... genital herpes . However, sometimes HSV-2 is spread to the ...

  16. Oral candidosis.

    PubMed

    McIntyre, G T

    2001-04-01

    Oral candidoses are frequently encountered in the practice of dentistry. Although most oral candidoses are symptomless, the can indicate the presence of an underlying systemic disease, and the persistence of oral candidosis following appropriate conventional management may be one of the first signs of undiagnosed immunosuppression. The opportunistic pathogen Candida albicans is the most commonly isolated species from oral candidal lesions; however, the non-albicans Candida spp. are also implicated in the aetiology of oral candidoses. The effective management of oral candidosis is dependent on an accurate diagnosis, identification and elimination of any predisposing factors (where possible), and the prescription of either topical or systemic antifungal agents. Oral candidosis may have significant implications for the general health of immunosuppressed patients, particularly when caused by the non-albicans spp. and, in cases of severe immunosuppression, systemic candidosis can be life-threatening. This article outlines the clinical presentation and appropriate management for the commonly presenting oral candidal conditions.

  17. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  18. Testosterone uptake by prostatic tissue from young and old rats.

    PubMed

    Ghanadian, R; Fotherby, K

    1975-01-01

    The uptake of [3H]-testosterone in vitro by the ventral lobe of the prostate of rats more than 11 months old was significantly less than that of rats 4-5 weeks old. There were significant decreases between young and old rats in the RNA and DNA content of the prostate but not in the activity of acid or alkaline phosphatases. Alkaline phosphatase activity was higher than that of acid phosphatase. Testosterone uptake by the prostate was higher in culture medium TC199 than in Krebs-Ringer buffer solution.

  19. Testosterone and pupillary response to auditory sexual stimuli.

    PubMed

    Dabbs, J M

    1997-10-01

    Low-, medium-, and high-testosterone subjects listened to four 30-s recorded stimuli while a computer system continuously measured their pupil size. The stimuli dealt with sex, aggression, and two neutral topics. Subjects dilated more to sex than to the other topics. Male and female subjects responded similarly, although low-testosterone males did not dilate as long as other subjects to the sexual stimulus. Auditory stimuli avoid a brightness artifact associated with visual stimuli. Auditory stimuli can be used in a variety of pupillometry studies, including studies of ongoing conversation and social interaction.

  20. Effects of testosterone therapy on bipolar disorder with Klinefelter syndrome.

    PubMed

    Kawahara, Kazuhiro; Jono, Tadashi; Nishi, Yoshitomo; Ushijima, Hirokage; Ikeda, Manabu

    2015-01-01

    Klinefelter syndrome (KS) is widely associated with cognitive impairment and language problems. KS patients may also exhibit psychiatric symptoms. We present the case of an 18-year-old man with KS who experienced rapidly repeating relapses of manic episodes. He was unresponsive to the usual pharmacotherapies for bipolar disorders such as mood stabilizers and second-generation antipsychotics. Mood was eventually improved with testosterone therapy in addition to pharmacotherapy, with no relapse of manic episodes for 3 years after discharge. Testosterone therapy may prevent relapsing manic episodes of bipolar disorder in patients with KS.

  1. Testosterone replacement for hypogonadism: clinical findings and best practices.

    PubMed

    Hengge, Ulrich R

    2003-12-01

    Hypogonadism is highly prevalent in HIV-infected patients and has been associated with the late stages of AIDS and AIDS wasting. There are a number of studies exploring treatment options. Testosterone replacement, with the exception of the transscrotal delivery patch, has been observed to have a beneficial effect on lean body mass and body weight in hypogonadal and eugonadal men with the AIDS wasting syndrome. Resistance exercise training also has had favorable effects on body weight and muscle cell mass. In hypogonadal men with AIDS treated with testosterone replacement therapy, researchers noted a positive effect on depression scores.

  2. 13C/12C isotope ratio MS analysis of testosterone, in chemicals and pharmaceutical preparations.

    PubMed

    de la Torre, X; González, J C; Pichini, S; Pascual, J A; Segura, J

    2001-02-01

    The 13C/12C ratio can be used to detect testosterone misuse in sport because (semi)-synthetic testosterone is supposed to have a 13C abundance different from that of endogenous natural human testosterone. In this study, gas chromatography/combustion isotope ratio mass spectrometry (GC/C/IRMS) analysis for the measurement of the delta 13C/1000 value of testosterone from esterified forms of 13 pharmaceutical preparations, six reagent grade chemicals and three bulk materials (raw materials used in pharmaceutical proarations) obtained world-wide was investigated after applying a strong acidic solvolytic procedure. Mean delta 13C/1000 values of non esterified (free) testosterone from chemicals and bulk materials of several testosterone esters were in the range: -25.91/-32.82/1000 while the value obtained for a (semi)-synthetic, reagent grade, free testosterone was -27.36/1000. The delta 13C/1000 results obtained for testosterone from the pharmaceuticals investigated containing testosterone esters were quite homogeneous (mean and S.D. of delta 13C/1000 values of free testosterone: 27.43 +/- 0.76/1000), being the range between -26.18 and -30.04/1000. Values described above were clearly different from those reported by several authors for endogenous natural human testosterone and its main metabolites excreted into the urine in non-consumers of testosterone (delta 13C/1000 range: from -21.3 to -24.4/1000), while they were similar to those of urinary testosterone and metabolites from individuals treated with testosterone esters and testosterone precursors. This finding justifies the fact that administration of these pharmaceutical formulations led to a statistical decrease of carbon isotope ratio of urinary testosterone and its main metabolites in treated subjects.

  3. The significance of biological variation in the diagnosis of testosterone deficiency, and consideration of the relevance of total, free and bioavailable testosterone determinations.

    PubMed

    Collier, Christine P; Morales, Alvaro; Clark, Albert; Lam, Miu; Wynne-Edwards, Katherine; Black, Angela

    2010-06-01

    The diagnosis of testosterone deficiency syndrome is based on clinical manifestations and documentation of low testosterone. Which biochemical tests to use and the importance of morning sampling are still controversial. Biological variation (including interindividual and intraindividual biological variation) must be considered when interpreting individual results as it determines the usefulness of reference intervals and the change (reference change value) necessary for a significant difference between results. A total of 87 healthy men (50 to 70+ years old) provided blood in the morning of the first day, and 4 weeks later in the morning and afternoon. Samples were frozen (-70C) and analyzed in the same run for serum testosterone, sex hormone-binding globulin and albumin, and bioavailable testosterone and free testosterone were calculated. Serum testosterone was lower in the afternoon by 1.5 nmol/l (43 ng/dl, p <0.05), with larger changes observed with higher morning values. However, this diurnal effect was dwarfed by the normal biological variation observed for repeat morning samples (serum testosterone +/- 4 nmol/l [115 ng/dl]). Between day intra-individual biological variation for morning serum testosterone was 18.7% while within day intra-individual biological variation was 12.9%. A change of 52% (reference change value) is necessary between serial morning results to confirm a significant difference. The biological variation parameters of calculated bioavailable testosterone and calculated free testosterone confer no advantage over total testosterone. Marked individuality of serum testosterone is evident even in healthy men. Because intraindividual biological variation is less than interindividual biological variation, reference intervals are marginally useful. The homeostatic set point of a patient could decrease by half and still be within the reference interval. Prospective establishment of an individual's baseline over repeated measurements or symptoms

  4. Effects of morphine on testosterone levels in rat C6 glioma cells: modulation by anastrozole.

    PubMed

    Ceccarelli, Ilaria; Rossi, Antonella; Maddalena, Melinda; Weber, Elisabetta; Aloisi, Anna Maria

    2009-10-01

    Rat C6 glioma cells are commonly used to investigate the functions of glial cells. To evaluate the presence of testosterone and its metabolism in rat C6 glioma cells, we cultured them in media with or without the addition of testosterone propionate and anastrozole, a blocker of aromatase, the enzyme needed to transform testosterone into estradiol. The same procedure was repeated with morphine (10 and 100 microM), known to decrease testosterone levels in the brain (in rats) and plasma (in rats and humans). Confluent cells were exposed to the test media for 48 h and then collected. Cell pellets were used to determine testosterone by radioimmunoassay. The C6 cells contained detectable levels of testosterone and the levels increased with the addition of testosterone to the medium. Aromatase blockage by anastrozole increased cellular levels of testosterone regardless of the addition of exogenous testosterone. Both concentrations of morphine dose-dependently decreased testosterone levels in the C6 cells; this effect was also present with the contemporary administration of anastrozole. Our findings show that testosterone is present in rat C6 glioma cells and can be metabolized by aromatase. Moreover, the presence of morphine in the culture medium strongly decreased testosterone, demonstrating that the glia would be a target of the morphine-induced hypogonadal effect.

  5. Testosterone and Child and Adolescent Adjustment: The Moderating Role of Parent-Child Relationships.

    ERIC Educational Resources Information Center

    Booth, Alan; Johnson, David R.; Granger, Douglas A.; Crouter, Ann C.; McHale, Susan

    2003-01-01

    In a sample of families with 6- to 18-year-olds, this study found that sons' and daughters' testosterone levels showed little direct connection to risk behavior or depressive symptoms. As parent-child relationship quality increased, testosterone-related adjustment problems were less evident. When relationship quality decreased, testosterone-linked…

  6. Marriage and motherhood are associated with lower testosterone concentrations in women.

    PubMed

    Barrett, Emily S; Tran, Van; Thurston, Sally; Jasienska, Grazyna; Furberg, Anne-Sofie; Ellison, Peter T; Thune, Inger

    2013-01-01

    Testosterone has been hypothesized to modulate the trade-off between mating and parenting effort in males. Indeed, evidence from humans and other pair-bonded species suggests that fathers and men in committed relationships have lower testosterone levels than single men and men with no children. To date, only one published study has examined testosterone in relation to motherhood, finding that mothers of young children have lower testosterone than non-mothers. Here, we examine this question in 195 reproductive-age Norwegian women. Testosterone was measured in morning serum samples taken during the early follicular phase of the menstrual cycle, and marital and maternal status were assessed by questionnaire. Mothers of young children (age ≤3) had 14% lower testosterone than childless women and 19% lower testosterone than women who only had children over age 3. Among mothers, age of the youngest child strongly predicted testosterone levels. There was a trend towards lower testosterone among married women compared to unmarried women. All analyses controlled for body mass index (BMI), age, type of testosterone assay, and time of serum sample collection. This is the first study to look at testosterone concentrations in relation to marriage and motherhood in Western women, and it suggests that testosterone may differ with marital and maternal status in women, providing further corroboration of previous findings in both sexes.

  7. Testosterone concentrations in early pregnancy: relation to method of conception in an infertile population.

    PubMed

    Lathi, Ruth B; Moayeri, Sharon E; Reddy, Charitha D; Gebhardt, Janice; Behr, Barry; Westphal, Lynn M

    2012-03-01

    This prospective cohort study of infertility patients compared testosterone concentrations in early pregnancy in infertility patients who conceived naturally or after treatment. Although all groups demonstrated some increase in pregnancy testosterone from baseline concentrations, subjects who conceived following ovulation induction showed a significantly increased rise in testosterone as compared with controls (P<0.01).

  8. Testosterone replacement does not normalize carcass composition in chronically decerebrate male rats.

    PubMed

    Harris, Ruth B S; Kelso, Emily W; Flatt, William P; Grill, Harvey J; Bartness, Timothy J

    2009-06-01

    Chronically decerebrate (CD) rats, in which the forebrain and its descending projections are completely neurally isolated from hindbrain and rostral projections, gain substantial amounts of body fat, lose lean tissue, and have low circulating testosterone concentrations. We tested whether testosterone replacement would normalize body composition of male CD rats. Five groups of rats were used: CD placebo, CD testosterone, control placebo, castrate placebo, and castrate testosterone. Testosterone replacement was initiated at the first stage of CD surgery in both CDs and castrate controls. The second stage of CD surgery occurred 8 days later, and the study ended 15 days later. Testosterone implants produced 10-fold normal circulating concentrations. Food intake was fixed for all rats by tube feeding. CD rats had substantially more body fat and less lean tissue than neurally intact rats. Testosterone replacement did not affect adiposity of CD rats but did increase carcass water content. Energy expenditure of CD rats was significantly lower than that of control placebo and castrated rats. Testosterone lowered respiratory equivalency ratio and ameliorated a fall in energy expenditure late in the intermeal interval in CD rats. Castration increased, and testosterone decreased luteinizing hormone (LH) and follicle stimulating hormone (FSH) in neurally intact controls. LH was undetectable, and FSH was equivalent to neurally intact controls in CD rats, and neither was affected by testosterone. Collectively, low testosterone did not explain obesity or decreased lean body mass of CD rats, although CD rats exhibited abnormal levels of circulating reproductive hormones and disrupted testosterone negative feedback.

  9. Testosterone and Child and Adolescent Adjustment: The Moderating Role of Parent-Child Relationships.

    ERIC Educational Resources Information Center

    Booth, Alan; Johnson, David R.; Granger, Douglas A.; Crouter, Ann C.; McHale, Susan

    2003-01-01

    In a sample of families with 6- to 18-year-olds, this study found that sons' and daughters' testosterone levels showed little direct connection to risk behavior or depressive symptoms. As parent-child relationship quality increased, testosterone-related adjustment problems were less evident. When relationship quality decreased, testosterone-linked…

  10. Marriage and motherhood are associated with lower testosterone concentrations in women

    PubMed Central

    Barrett, Emily S.; Tran, Van; Thurston, Sally; Jasienska, Grazyna; Furberg, Anne-Sofie; Ellison, Peter T.; Thune, Inger

    2012-01-01

    Testosterone has been hypothesized to modulate the trade-off between mating and parenting effort in males. Indeed, evidence from humans and other pair-bonded species suggests that fathers and men in committed relationships have lower testosterone levels than single men and men with no children. To date, only one published study has examined testosterone in relation to motherhood, finding that mothers of young children have lower testosterone than non-mothers. Here, we examine this question in 195 reproductive-age Norwegian women. Testosterone was measured in morning serum samples taken during the early follicular phase of the menstrual cycle, and marital and maternal status were assessed by questionnaire. Mothers of young children (age ≤3) had 14% lower testosterone than childless women and 19% lower testosterone than women who only had children over age 3. Among mothers, age of the youngest child strongly predicted testosterone levels. There was a trend towards lower testosterone among married women compared to unmarried women. All analyses controlled for body mass index (BMI), age, type of testosterone assay, and time of serum sample collection. This is the first study to look at testosterone concentrations in relation to marriage and motherhood in Western women, and it suggests that testosterone may differ with marital and maternal status in women, providing further corroboration of previous findings in both sexes. PMID:23123222

  11. Has testosterone passed the test in premenopausal women with low libido? A systematic review

    PubMed Central

    Reed, Beverly G; Bou Nemer, Laurice; Carr, Bruce R

    2016-01-01

    Background There are limited evaluation and treatment options for low libido in premenopausal women. This review sought to evaluate the available evidence supporting the evaluation of testosterone serum levels and testosterone treatment of premenopausal women with low libido. Methods MEDLINE, PubMed, and ClinicalTrials.gov were searched for articles that referenced the evaluation of testosterone serum level and/or testosterone treatment on premenopausal women with low libido from 1995 to 2015. Additional references were obtained from the reference sections of other papers and from peer review. Studies that included only postmenopausal women were excluded. A total of 13 studies were reviewed in detail. Nine studies examined the relationship between testosterone serum levels and sexuality, an additional three studies examined the effect of testosterone treatment on premenopausal women with low libido, and one study examined both the topics. Results Six of the ten testosterone serum evaluation studies failed to show a significant association between testosterone serum level and libido. Only one out of four studies examining testosterone treatment in premenopausal women was able to show any clear improvement in libido; however, the effect was limited to only the intermediate dose of testosterone, with the low and high doses of testosterone not producing any effect. Conclusion The currently available evidence does not support testosterone serum evaluation or treatment in premenopausal women with low libido. Hence, further studies are warranted. PMID:27785108

  12. Effect of prenatal and natal administration of testosterone on production of structurally based plumage coloration.

    PubMed

    Siefferman, Lynn; Liu, Mark; Navara, Kristen J; Mendonça, Mary T; Hill, Geoffrey E

    2013-01-01

    Testosterone has been implicated as a developmental mechanism involved in the organization and expression of sexually dimorphic traits, such as plumage coloration, in birds. Although research findings relating testosterone levels to plumage expression is equivocal, few studies have investigated how testosterone may influence the expression of structurally based plumage coloration. Here, we use experimental and correlational evidence to test the hypothesis that testosterone influences the development and maintenance of structurally based plumage coloration in a wild-breeding population of eastern bluebirds (Sialia sialis). First, we experimentally manipulated yolk testosterone and measured the effect on the development of plumage coloration of nestlings. Second, we implanted juvenile bluebirds with testosterone and measured the effect on nestling growth, body condition, and plumage coloration of nestlings. Third, we measured covariation between circulating testosterone and plumage coloration of breeding males. Yolk testosterone injections had no significant effect on nestling plumage coloration. Testosterone implantation, however, caused a reduction in plumage brightness, elevated corticosterone, and slower growth in nestlings. Finally, in breeding adult males we found no significant relationship between structural coloration and testosterone; however, males with higher testosterone levels exhibited duller chestnut (melanin-based) plumage. Our observations lead us to reject the hypothesis that testosterone increases structural plumage coloration in male eastern bluebirds.

  13. Separating behavioral and physiological mechanisms in testosterone-mediated trade-offs.

    PubMed

    Mougeot, François; Redpath, Stephen M; Piertney, Stuart B; Hudson, Peter J

    2005-08-01

    Testosterone often mediates trade-offs between reproduction and other life-history traits, which are usually investigated using testosterone implants. However, this approach does not distinguish between the physiological and behavioral effects of testosterone. We studied a wild game bird, the red grouse Lagopus lagopus scoticus, and took a new approach to investigate mechanisms linking elevated testosterone to increased parasite intensity. We caught males in autumn, removed their parasites, implanted them with the antiandrogen flutamide in combination with an aromatase inhibitor (FA males) or with empty implants (control males), and challenged them with parasites. The FA treatment increased testosterone concentration and physiological stress, but without enhancing testosterone-dependent behaviors, because testosterone receptors were blocked. FA males ended up with more parasites than the control males the following autumn, an effect similar to that of a testosterone treatment reported elsewhere. However, and unlike the testosterone treatment, the FA treatment did not affect home range, pairing, or breeding success. The results supported a physiological mechanism (increased susceptibility) linking elevated testosterone and increased parasite intensity. The FA treatment provided a new way of investigating testosterone-mediated trade-offs whereby testosterone concentration was increased while the effects on behavior were blocked, resulting in physiological costs without phenotypic benefits.

  14. Endogenous testosterone level and testosterone supplementation therapy in chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis

    PubMed Central

    Atlantis, Evan; Fahey, Paul; Cochrane, Belinda; Wittert, Gary; Smith, Sheree

    2013-01-01

    Objective Low testosterone level may be a reversible risk factor for functional disability and deterioration in patients with chronic obstructive pulmonary disease (COPD). We sought to systematically assess the endogenous testosterone levels and effect of testosterone therapy on exercise capacity and health-related quality of life (HRQoL) outcomes in COPD patients, as well as to inform guidelines and practice. Design Systematic review and meta-analysis. Data sources We searched PubMed, Scopus, Cochrane Library, CINAHL, Health Source Nursing and PsychINFO and the reference lists of retrieved articles published before May 2012. Inclusion criteria Observational studies on endogenous testosterone levels in people with chronic lung disease compared with controls, or randomised controlled trials (RCTs) on testosterone therapy for exercise capacity and/or HRQoL outcomes in COPD patients were eligible. Data extraction and analysis Data on the mean difference in endogenous total testosterone (TT) values, and the mean difference in exercise capacity and HRQoL values were extracted and pooled using random effects meta-analysis. Results Nine observational studies in 2918 men with COPD reported consistently lower levels of TT compared with controls (weighted mean difference was –3.21 nmol/L (95% CI −5.18 to −1.23)). Six RCTs in 287 participants yielded five studies on peak muscle strength and peak cardiorespiratory fitness outcomes (peak oxygen uptake (VO2) and workload) and three studies on HRQoL outcomes. Testosterone therapies significantly improved peak muscle strength (standardised mean difference (SMD) was 0.31 (95% CI 0.05 to 0.56)) and peak workload (SMD was 0.27 (95% CI 0.01 to 0.52)) compared with control conditions (all but one used placebo), but not peak VO2 (SMD was 0.21 (95% CI −0.15 to 0.56)) or HRQoL (SMD was –0.03 (95% CI −0.32 to 0.25)). Conclusions Men with COPD have clinically relevant lower than normal TT levels. Insufficient evidence from

  15. Endogenous testosterone level and testosterone supplementation therapy in chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis.

    PubMed

    Atlantis, Evan; Fahey, Paul; Cochrane, Belinda; Wittert, Gary; Smith, Sheree

    2013-08-13

    Low testosterone level may be a reversible risk factor for functional disability and deterioration in patients with chronic obstructive pulmonary disease (COPD). We sought to systematically assess the endogenous testosterone levels and effect of testosterone therapy on exercise capacity and health-related quality of life (HRQoL) outcomes in COPD patients, as well as to inform guidelines and practice. Systematic review and meta-analysis. We searched PubMed, Scopus, Cochrane Library, CINAHL, Health Source Nursing and PsychINFO and the reference lists of retrieved articles published before May 2012. Observational studies on endogenous testosterone levels in people with chronic lung disease compared with controls, or randomised controlled trials (RCTs) on testosterone therapy for exercise capacity and/or HRQoL outcomes in COPD patients were eligible. Data on the mean difference in endogenous total testosterone (TT) values, and the mean difference in exercise capacity and HRQoL values were extracted and pooled using random effects meta-analysis. Nine observational studies in 2918 men with COPD reported consistently lower levels of TT compared with controls (weighted mean difference was -3.21 nmol/L (95% CI -5.18 to -1.23)). Six RCTs in 287 participants yielded five studies on peak muscle strength and peak cardiorespiratory fitness outcomes (peak oxygen uptake (VO2) and workload) and three studies on HRQoL outcomes. Testosterone therapies significantly improved peak muscle strength (standardised mean difference (SMD) was 0.31 (95% CI 0.05 to 0.56)) and peak workload (SMD was 0.27 (95% CI 0.01 to 0.52)) compared with control conditions (all but one used placebo), but not peak VO2 (SMD was 0.21 (95% CI -0.15 to 0.56)) or HRQoL (SMD was -0.03 (95% CI -0.32 to 0.25)). Men with COPD have clinically relevant lower than normal TT levels. Insufficient evidence from short-term studies in predominately male COPD patients suggests that testosterone therapy improves exercise

  16. Low Testosterone Correlates with Delayed Development in Male Orangutans

    PubMed Central

    Emery Thompson, Melissa; Zhou, Amy; Knott, Cheryl D.

    2012-01-01

    Male orangutans (Pongo spp.) display an unusual characteristic for mammals in that some adult males advance quickly to full secondary sexual development while others can remain in an adolescent-like form for a decade or more past the age of sexual maturity. Remarkably little is understood about how and why differences in developmental timing occur. While fully-developed males are known to produce higher androgen levels than arrested males, the longer-term role of steroid hormones in male life history variation has not been examined. We examined variation in testosterone and cortisol production among 18 fully-developed (“flanged”) male orangutans in U.S. captive facilities. Our study revealed that while testosterone levels did not vary significantly according to current age, housing condition, and species origin, males that had undergone precocious development had higher testosterone levels than males that had experienced developmental arrest. While androgen variation had previously been viewed as a state-dependent characteristic of male developmental status, our study reveals that differences in the physiology of early and late developing males are detectable long past the developmental transition and may instead be trait-level characteristics associated with a male’s life history strategy. Further studies are needed to determine how early in life differences in testosterone levels emerge and what consequences this variation may have for male behavioral strategies. PMID:23077585

  17. Low testosterone correlates with delayed development in male orangutans.

    PubMed

    Emery Thompson, Melissa; Zhou, Amy; Knott, Cheryl D

    2012-01-01

    Male orangutans (Pongo spp.) display an unusual characteristic for mammals in that some adult males advance quickly to full secondary sexual development while others can remain in an adolescent-like form for a decade or more past the age of sexual maturity. Remarkably little is understood about how and why differences in developmental timing occur. While fully-developed males are known to produce higher androgen levels than arrested males, the longer-term role of steroid hormones in male life history variation has not been examined. We examined variation in testosterone and cortisol production among 18 fully-developed ("flanged") male orangutans in U.S. captive facilities. Our study revealed that while testosterone levels did not vary significantly according to current age, housing condition, and species origin, males that had undergone precocious development had higher testosterone levels than males that had experienced developmental arrest. While androgen variation had previously been viewed as a state-dependent characteristic of male developmental status, our study reveals that differences in the physiology of early and late developing males are detectable long past the developmental transition and may instead be trait-level characteristics associated with a male's life history strategy. Further studies are needed to determine how early in life differences in testosterone levels emerge and what consequences this variation may have for male behavioral strategies.

  18. EMAS position statement: Testosterone replacement therapy in the aging male‏.

    PubMed

    Dimopoulou, Christina; Ceausu, Iuliana; Depypere, Herman; Lambrinoudaki, Irene; Mueck, Alfred; Pérez-López, Faustino R; Rees, Margaret; van der Schouw, Yvonne T; Senturk, Levent M; Simonsini, Tommaso; Stevenson, John C; Stute, Petra; Goulis, Dimitrios G

    2016-02-01

    Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. Literature review and consensus of expert opinion. Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Fate of estradiol and testosterone in anaerobic lagoon digestors

    USDA-ARS?s Scientific Manuscript database

    Laboratory-scale lagoon digestors were constructed, and the fate of 14C-labelled 17ß-estradiol (E2) and testosterone (Test) were monitored for 42 d anaerobically under biological and sterile conditions. Hormone levels decreased in the liquid layer and increased in the sludge with time. At 42 d, 16-2...

  20. Foetal Testosterone, Social Relationships, and Restricted Interests in Children

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca; Baron-Cohen, Simon; Raggatt, Peter; Taylor, Kevin

    2005-01-01

    Background: Sex-differences exist in some areas of human social behaviour. In animals, foetal testosterone (fT) plays a central role in organising the brain and in later social behaviour. fT has also been implicated in language development, eye-contact, and spatial ability in humans. Methods: Fifty-eight children (35 male and 23 female), whose fT…

  1. Second-to-Fourth Digit Length, Testosterone and Spatial Ability

    ERIC Educational Resources Information Center

    Kempel, P.; Gohlke, B.; Klempau, J.; Zinsberger, P.; Reuter, M.; Hennig, J.

    2005-01-01

    Based on stimulating findings suggesting that prenatal levels of steroids may influence cognitive functions, a study with N=40 healthy volunteers of both sexes was conducted. Prenatal levels of testosterone (T) were estimated by use of the second-to-fourth digit ratio (2D:4D) which is supposed to be controlled by the same genes involved in…

  2. IQ, Fetal Testosterone and Individual Variability in Children's Functional Lateralization

    ERIC Educational Resources Information Center

    Mercure, Evelyne; Ashwin, Emma; Dick, Frederic; Halit, Hanife; Auyeung, Bonnie; Baron-Cohen, Simon; Johnson, Mark H.

    2009-01-01

    Previous event-related potential (ERP) studies have revealed that faces and words show a robust difference in the lateralization of their N170. The present study investigated the development of this differential lateralization in school-age boys. We assessed the potential role of fetal testosterone (FT) level as a factor biasing the prenatal…

  3. Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

    PubMed Central

    Barone, Rosario; Marino Gammazza, Antonella; Sangiorgi, Claudia; Barone, Fulvio; Pitruzzella, Alessandro; Locorotondo, Nicola; Di Gaudio, Francesca; Salerno, Monica; Maglietta, Francesca; Sarni, Antonio Luciano; Di Felice, Valentina; Cappello, Francesco; Turillazzi, Emanuela

    2015-01-01

    Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin‐releasing hormone, luteinizing hormone, and follicle‐stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real‐time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the basal level a 15.6 μM dose of nandrolone. Nandrolone‐induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a‐hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down‐regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects. J. Cell. Physiol. 231: 1385–1391, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:26626779

  4. EFFECTS OF ENVIRONMENTAL CHEMICALS ON FETAL TESTES TESTOSTERONE PRODUCTION

    EPA Science Inventory

    Effects of Environmental Chemicals on Fetal Testes Testosterone Production

    Lambright, CS , Wilson, VS , Furr, J, Wolf, CJ, Noriega, N, Gray, LE, Jr.
    US EPA, ORD/NHEERL/RTD, RTP, NC

    Exposure of pregnant rodents to certain environmental chemicals during criti...

  5. Foetal Testosterone, Social Relationships, and Restricted Interests in Children

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca; Baron-Cohen, Simon; Raggatt, Peter; Taylor, Kevin

    2005-01-01

    Background: Sex-differences exist in some areas of human social behaviour. In animals, foetal testosterone (fT) plays a central role in organising the brain and in later social behaviour. fT has also been implicated in language development, eye-contact, and spatial ability in humans. Methods: Fifty-eight children (35 male and 23 female), whose fT…

  6. Second-to-Fourth Digit Length, Testosterone and Spatial Ability

    ERIC Educational Resources Information Center

    Kempel, P.; Gohlke, B.; Klempau, J.; Zinsberger, P.; Reuter, M.; Hennig, J.

    2005-01-01

    Based on stimulating findings suggesting that prenatal levels of steroids may influence cognitive functions, a study with N=40 healthy volunteers of both sexes was conducted. Prenatal levels of testosterone (T) were estimated by use of the second-to-fourth digit ratio (2D:4D) which is supposed to be controlled by the same genes involved in…

  7. EFFECTS OF ENVIRONMENTAL CHEMICALS ON FETAL TESTES TESTOSTERONE PRODUCTION

    EPA Science Inventory

    Effects of Environmental Chemicals on Fetal Testes Testosterone Production

    Lambright, CS , Wilson, VS , Furr, J, Wolf, CJ, Noriega, N, Gray, LE, Jr.
    US EPA, ORD/NHEERL/RTD, RTP, NC

    Exposure of pregnant rodents to certain environmental chemicals during criti...

  8. Testosterone and human performance: influence of the color red.

    PubMed

    Hackney, A C

    2006-02-01

    This study examined the testosterone responses of men to an exercise bout simulating a competitive sporting effort in order to determine if the wearing of red-colored apparel influenced the hormonal response. Male subjects (n = 10) were placed into sets of matched-pairs and performed VO(2max) cycle ergometry exercise test to exhaustion to simulate the competitive effort. Each member of a pairing was randomly assigned to one of two treatment groups-the wearing of red-colored clothing, or the wearing of black-colored clothing. Blood samples were collected before exercise (REST), an immediate postexercise sample was collected at exhaustion (EXH), and a final sample was taken at 15 min into recovery (REC) from exercise. Blood was biochemically analyzed for total testosterone. In response to the exercise, performance characteristics (i.e., VO(2max) and maximal workload) of treatment groups did not differ significantly. A significant increase (P < 0.01) in the testosterone was observed in both treatment groups postexercise at EXH and at REC as compared to REST. However, no differences were observed between treatment groups in the before or postexercise hormonal concentrations. These findings suggest that the wearing of red-colored apparel had no affects on the testosterone responses to an exercise bout simulating a competition.

  9. IQ, Fetal Testosterone and Individual Variability in Children's Functional Lateralization

    ERIC Educational Resources Information Center

    Mercure, Evelyne; Ashwin, Emma; Dick, Frederic; Halit, Hanife; Auyeung, Bonnie; Baron-Cohen, Simon; Johnson, Mark H.

    2009-01-01

    Previous event-related potential (ERP) studies have revealed that faces and words show a robust difference in the lateralization of their N170. The present study investigated the development of this differential lateralization in school-age boys. We assessed the potential role of fetal testosterone (FT) level as a factor biasing the prenatal…

  10. Aromatized testosterone attenuates contextual generalization of fear in male rats.

    PubMed

    Lynch, Joseph F; Vanderhoof, Tyler; Winiecki, Patrick; Latsko, Maeson S; Riccio, David C; Jasnow, Aaron M

    2016-08-01

    Generalization is a common symptom of many anxiety disorders, and females are 60% more likely to suffer from an anxiety disorder than males. We have previously demonstrated that female rats display significantly accelerated rates of contextual fear generalization compared to male rats; a process driven, in part, by activation of ERβ. The current study was designed to determine the impact of estrogens on contextual fear generalization in male rats. For experiment 1, adult male rats were gonadectomized (GDX) and implanted with a capsule containing testosterone proprionate, estradiol, dihydrotestosterone proprionate (DHT), or an empty capsule. Treatment with testosterone or estradiol maintained memory precision when rats were tested in a different (neutral) context 1day after training. However, male rats treated with DHT or empty capsules displayed significant levels of fear generalization, exhibiting high levels of fear in the neutral context. In Experiment 2, we used acute injections of gonadal hormones at a time known to elicit fear generalization in female rats (e.g. 24h before testing). Injection treatment followed the same pattern of results seen in Experiment 1. Finally, animals given daily injections of the aromatase inhibitor, Fadrozole, displayed significant fear generalization. These data suggest that testosterone attenuates fear generalization likely through the aromatization testosterone into estradiol as animals treated with the non-aromatizable androgen, DHT, or animals treated with Fadrozole, displayed significant generalized fear. Overall, these results demonstrate a sex-dependent effect of estradiol on the generalization of contextual fear. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. A longitudinal analysis of women's salivary testosterone and intrasexual competitiveness.

    PubMed

    Hahn, Amanda C; Fisher, Claire I; Cobey, Kelly D; DeBruine, Lisa M; Jones, Benedict C

    2016-02-01

    Research on within-subject changes in women's intrasexual competitiveness has generally focused on possible relationships between women's intrasexual competitiveness and estimates of their fertility. While this approach is useful for testing hypotheses about the adaptive function of changes in women's intrasexual competitiveness, it offers little insight into the proximate mechanisms through which such changes might occur. To investigate this issue, we carried out a longitudinal study of the hormonal correlates of changes in intrasexual competitiveness in a large sample of heterosexual women (N=136). Each woman provided saliva samples and completed an intrasexual competitiveness questionnaire in five weekly test sessions. Multilevel modeling of these data revealed a significant, positive within-subject effect of testosterone on intrasexual competitiveness, indicating that women reported greater intrasexual competitiveness when testosterone was high. By contrast, there were no significant effects of estradiol, progesterone, estradiol-to-progesterone ratio, or cortisol and no significant effects of any hormones on reported relationship jealousy. This is the first study to demonstrate correlated changes in measured testosterone levels and women's reported intrasexual competitiveness, implicating testosterone in the regulation of women's intrasexual competitiveness. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  12. [Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].

    PubMed

    Gonzales, Gustavo F

    2011-03-01

    The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

  13. Hostility, testosterone, and vascular reactivity to stress: effects of sex.

    PubMed

    Girdler, S S; Jammer, L D; Shapiro, D

    1997-01-01

    This study investigated the association of personality with cardiovascular stress reactivity (CVR) in men and women. Also, the degree to which testosterone and estradiol reactivity were related to personality and CVR measures was examined. Twenty-six men and 44 women completed the Cook-Medley Hostility Scale, the Beck Depression Inventory, and the Spielberger Trait Anxiety Inventory before speech, Stroop, and math stress. Testosterone (men) and estradiol (subset of women) were sampled once after an initial rest period and again after the last stressor. Cardiovascular reactivity, including cardiac output and total peripheral resistance (TPR), was assessed during stressors. For men, testosterone increased significantly with stress, and testosterone reactivity to stressors was significantly correlated with hostility. However, stepwise multiple regression revealed that hostility was the only independent predictor of CVR to speech, math, and Stroop stress in men, accounting for 13%-32% of the variance in TPR. Baseline systolic blood pressure explained 22% of the variance in TPR reactivity to speech preparation. No evidence was obtained to suggest that hostility, depressive mood, or anxiety predicted CVR in women, and estradiol did not show stress-sensitive effects. These data provide evidence that increased vascular reactivity may be one mechanism linking hostility to increased cardiovascular mortality in men and support the notion that hostility may have different implications for CVR in women.

  14. No effect of testosterone on behavior in aged Wistar rats

    PubMed Central

    Borbélyová, Veronika; Domonkos, Emese; Bábíčková, Janka; Tóthová, Ľubomíra; Bosý, Martin; Hodosy, Július; Celec, Peter

    2016-01-01

    In men, aging is accompanied by a gradual decline in androgen secretion. Studies suggest beneficial effects of endogenous and exogenous testosterone on affective behavior and cognitive functions. The aim of this study was to describe behavioral and cognitive sex differences and to analyze the effects of long-term androgen deficiency in aged male rats. Thirty-months old rats divided into three groups (males, females and males gonadectomized as young adults) underwent a battery of behavioral tests assessing locomotor activity, anxiety, memory, anhedonia, sociability and depression-like behavior. No major effect of gonadectomy was found in any of the analyzed behavioral measures in male rats. The only consistent sex difference was confirmed in depression-like behavior with longer immobility time observed in males. In an interventional experiment, a single dose of testosterone had no effect on gonadectomized male and female rats in the forced swim test. In contrast to previous studies this comprehensive behavioral phenotyping of aged rats revealed no major role of endogenous testosterone. Based on our results long-term hypogonadism does not alter the behavior of aged male rats, neither does acute testosterone treatment. Whether these findings have any consequences on androgen replacement therapy in aged men remains to be elucidated. PMID:27852981

  15. Effects of Testosterone Administration on Strategic Gambling in Poker Play

    PubMed Central

    van Honk, Jack; Will, Geert-Jan; Terburg, David; Raub, Werner; Eisenegger, Christoph; Buskens, Vincent

    2016-01-01

    Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone’s primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players’ bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one’s reputation by revealing deceptive intent, and secondly, not calling the other players’ bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous. PMID:26727636

  16. Pituitary and testis responsiveness of young male sheep exposed to testosterone excess during fetal development.

    PubMed

    Recabarren, Mónica P; Rojas-Garcia, Pedro P; Einspanier, Ralf; Padmanabhan, Vasantha; Sir-Petermann, Teresa; Recabarren, Sergio E

    2013-06-01

    Prenatal exposure to excess testosterone induces reproductive disturbances in both female and male sheep. In females, it alters the hypothalamus-pituitary-ovarian axis. In males, prenatal testosterone excess reduces sperm count and motility. Focusing on males, this study tested whether pituitary LH responsiveness to GNRH is increased in prenatal testosterone-exposed males and whether testicular function is compromised in the testosterone-exposed males. Control males (n=6) and males born to ewes exposed to twice weekly injections of 30  mg testosterone propionate from days 30 to 90 and of 40  mg testosterone propionate from days 90 to 120 of gestation (n=6) were studied at 20 and 30 weeks of age. Pituitary and testicular responsiveness was tested by administering a GNRH analog (leuprolide acetate). To complement the analyses, the mRNA expression of LH receptor (LHR) and that of steroidogenic enzymes were determined in testicular tissue. Basal LH and testosterone concentrations were higher in the testosterone-exposed-males. While LH response to the GNRH analog was higher in the testosterone-exposed males than in the control males, testosterone responses did not differ between the treatment groups. The testosterone:LH ratio was higher in the control males than in the testosterone-exposed males of 30 weeks of age, suggestive of reduced Leydig cell sensitivity to LH in the testosterone-exposed males. The expression of LHR mRNA was lower in the testosterone-exposed males, but the mRNA expression of steroidogenic enzymes did not differ between the groups. These findings indicate that prenatal testosterone excess has opposing effects at the pituitary and testicular levels, namely increased pituitary sensitivity to GNRH at the level of pituitary and decreased sensitivity of the testes to LH.

  17. Diagnosis and Treatment of Low Testosterone among patients with End-Stage Renal Disease

    PubMed Central

    Bao, Yeran; Johansen, Kirsten L.

    2015-01-01

    The prevalence of low testosterone level is particularly high among patients with end-stage renal disease (ESRD) and has been associated with mortality. In populations without ESRD, low testosterone level has also been associated with a number of morbidities including cardiovascular disease, diabetes mellitus, low muscle mass, low bone mass, low physical performance, and frailty. However, there is controversy regarding what constitutes low testosterone level in the aging population and at what level replacement therapy with testosterone is indicated. There are no randomized controlled trials investigating long-term outcomes of testosterone replacement therapy in populations with or without ESRD. Available trial results suggest equivocal improvements in sexual function. Muscle mass and bone mineral density appear to improve but results in physical function and performance are mixed and there are no data on fracture prevention. Some recent data suggest harm when testosterone was given to men with limited mobility. Finally, there is little evidence that testosterone adds to existing erythropoietin agents in the treatment of anemia in ESRD. Due to lack of evidence supporting long-term use of testosterone, the authors recommend against the routine use of testosterone in ESRD patients with low testosterone levels. Testosterone treatment can be considered in those with low bone mass and total testosterone level less than 200 ng/dL, or in younger patients with sexual complaints with total testosterone level lower than the reference range. It is important to engage patients in discussion of risks and benefits before initiating testosterone therapy; testosterone therapy should be discontinued if the intended treatment effect is not observed after short-term use. PMID:25376701

  18. Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials.

    PubMed

    Gagliano-Jucá, Thiago; Içli, Tevhide Betül; Pencina, Karol M; Li, Zhuoying; Tapper, John; Huang, Grace; Travison, Thomas G; Tsitouras, Panayiotis; Harman, S Mitchell; Storer, Thomas W; Bhasin, Shalender; Basaria, Shehzad

    2017-05-01

    Endogenous testosterone levels have been negatively associated with QTc interval in small ca