Testosterone has been used therapeutically for over 70 years in men suffering from the symptoms of testosterone deficiency (TD, hypogonadism), and a strong body of evidence suggests testosterone treatment is safe and efficacious in patients for whom it is indicated. Additionally, there exists sufficient data to recognize male hypogonadism as a risk factor for cardiovascular disease. Four recently published studies suggested that testosterone therapy is associated with myocardial infarction, stroke, and death. Although these studies are afflicted with poor study design, flawed data analysis and misinterpretations, and received nearly unanimous rejection by experts in the field, the mainstream media has catapulted the studies into the public spotlight with sensationalist headlines, creating a hysteria that has had far-reaching and dangerous implications for patients and physicians. The media-driven hysteria has created an environment in which pharmaceutical companies are being sued, physicians are withholding treatment from men suffering from testosterone deficiency, and the United States Food and Drug Administration has been petitioned to place a black box warning on testosterone products. The imbalanced media coverage has crossed a grave ethical line by interfering in the patient-physician relationship to the extent that patients are being harmed.

Proliferative responses of normal rat ventral prostate in vitro were investigated using the incorporation of 5-[125I]-iodo-2'-deoxyuridine (125I-UdR) to monitor DNA synthesis, with the aim of establishing a model system for evaluating the direct effects of hormones and chemotherapeutic agents on prostatic growth. In androgen-free, chemically-defined organ culture, the proliferative activity of young adult rat (4 to 6 months old) ventral prostate declined with time and the tissue underwent retrogressive changes resembling post-castration atrophy in vivo. Treatment with testosterone (4 x 10-12 to 4 x 10-5M) exhibited a dose-dependent response, with concentrations ranging from 4 x 10-9to 4 x 10-6M preventing the retrogressive changes associated with androgen deprivation and eliciting maximal increases (approximately 3-fold) in 125I-Udr uptake. Higher testosterone concentrations (2.5 x 10-5 to 4 x 10-5M) exerted a non-specific cytotoxic effect, resulting in marked suppression of 125I-Udr uptake. Following stimulation with an optimal concentration of testosterone (4 x 10-7M), 125I-Udr incorporation reached peak activity on day 4 of the culture period and rapidly declined thereafter, despite the continued presence of testosterone. Effects of variations in organ culture media and methodology were also examined to further establish optimal conditions for investigations of the proliferative response to testosterone stimulation. The established method of quantitative organ culture was then used to compare the proliferative effect of testosterone with that of its major metabolites, 5α-dihydrotestosterone, androstenedione, androstenedione and 5α-androstane-3β, 17β-diol.

Orientador: Jacks Jorge Junior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-20T02:57:10Z (GMT). No. of bitstreams: 1 Hopp_RenatoNicolas_D.pdf: 2089975 bytes, checksum: a53b427e5a17e243fecc17545189419c (MD5) Previous issue date: 2012 / Resumo: Estudos sugerem que a exposição pré-natal à testosterona (PT) está relacionada à inteligência ou à capacidade de aprendizado. A proporção entre os dedos indicador e anelar (proporção digital ou 2D:4D) correlaciona-se negativamente à exposição pré-natal à testosterona. Este estudo avaliou as correlações entre o 2D:4D e o sucesso acadêmico em disciplinas teóricas e práticas no currículo do curso de Odontologia da Faculdade de Odontologia de Piracicaba da Universidade Estadual de Campinas, Brasil. Ao todo, 80 indivíduos (40 homens e 40 mulheres) com idade entre 18 e 22 anos (média 19,5 ± 1,1 anos para os homens e 19,7 ± 1,2 para mulheres), alunos do 2º ao 4º ano de graduação tiveram sua mão direita fotografada por meio de câmera digital acoplada a dispositivo padronizador perpendicular à superfície. As imagens foram transferidas ao software Adobe Photoshop® e os dedos indicador e anelar foram medidos de forma linear, da depressão mais caudal ao ponto mais rostral da ponta do dedo. Os dados foram analisados usando os softwares Microsoft Excel, SPSS 16 e Statview. A proporção digital média foi de 0,980 ± 0,038 para homens e 0,991 ± 0,025 para mulheres. Correlacionou-se então esta proporção às notas teóricas e práticas obtidas pelos estudantes durante os primeiros quatro semestres letivos do curso. As notas teóricas e práticas foram negativamente correlacionadas à proporção digital em homens (especialmente após a remoção da influência das horas de estudo domésticas; p = 0,02 e 0,004, respectivamente), mas não em mulheres (p = 0,89 e 0,77, respectivamente). Este achado apóia a correlação entre a influência da testosterona pré-natal e o desenvolvimento da inteligência em homens. A falta de correlação entre a testosterona pré-natal e o sucesso acadêmico em mulheres sugere que a inteligência no sexo feminino deve ser influenciada por fatores alheios à testosterona pré-natal / Abstract: It has been suggested that prenatal testosterone (PT) is positively related to intelligence or learning-ability skills. Digit ratio (2D:4D) is a negative correlate of PT. This study considered the correlations between 2D:4D and academic success in practical and theoretical disciplines in the Dental School curriculum of the Piracicaba Dental School, State University of Campinas, Brazil. Overall, 80 subjects (40 males and 40 females) aged between 18 and 22 years (means 19.5 ± 1.1 and 19.7 ± 1.2, respectively) had their right hand palm photographed by a digital camera attached to a standardising device, perpendicular to the surface. The images were transferred to a computer and the index and ring fingers were measured from the ventralmost crease up to the tip of the finger using Adobe Photoshop. Data were analyzed using Microsoft Excel and SPSS 16. Mean digit ratio was 0.980 ± 0.038 for males and 0.991 ± 0.025 for females. Digit ratio was correlated to the grades obtained by the students through their first four semesters. Theoretical and practical grades were significantly negatively correlated to digit ratio in males (and this was particularly so after the influence of age and hours of study were removed, p = 0.02 and 0.004, respectively), but not in females (p = 0.89 and 0.77, respectively). This finding supports a link between high PT and intelligence in males. The lack of relationship between 2D:4D and examination marks in female students, suggests that intelligence in females may be influenced by factors other than prenatal testosterone / Doutorado / Patologia / Doutor em Estomatopatologia

Aromatase, a member of the cytochrome P450 superfamily, catalyses the conversion of androgens to estrogens; specifically, testosterone to estradiol and androstenedione to estrone. Aromatase is widely expressed across a range of tissues and deleterious metabolic effects are observed in both murine aromatase knock-out models and in rare human cases of aromatase deficiency. The effects of pharmacological inhibition of aromatase, as employed in the treatment of breast cancer, are not well characterised. This thesis addresses the hypothesis that aromatase inhibition, and consequent changes in sex steroid hormone action (higher androgen:estrogen ratio), results in disadvantageous changes in body composition and reduced insulin sensitivity. In a cohort study of 197 community-dwelling men, lower testosterone and SHBG concentrations were observed in those fulfilling criteria for metabolic syndrome, although no relationship with estrogens was observed. The strongest determinant of circulating estrogens was substrate androgen concentration. A case-control study of aromatase inhibitor treated breast cancer patients and age-matched controls (n=40) demonstrated decreased insulin sensitivity and increased body fat in those treated with aromatase inhibitors; serum leptin concentration and leptin mRNA transcript levels (in subcutaneous adipose tissue) were elevated in this group. In healthy male volunteers (n=17), 6 weeks of aromatase inhibition (1 mg anastrozole daily) resulted in reduced glucose disposal during a hyperinsulinaemic euglycaemic clamp study, with d2-glucose and d5-glycerol tracers. No effects upon hepatic insulin sensitivity, lipolysis or body composition were noted, although serum leptin concentration was reduced following aromatase inhibitor administration. In conclusion, aromatase inhibition is associated with increased insulin resistance and, in women, increased body fat. This may be relevant for patients receiving aromatase inhibitor therapy, where more careful monitoring of glucose tolerance may be warranted.

Male stickleback did not show a greater increase in displacement or parental fanning when injected with prolactin than they did when injected with saline solvent alone. Displacement fanning was higher in gonadectomized fish with pituitary activity suppressed by short photoperiod than in gonadectomized fish with an active pituitary under long photoperiods when both groups were treated with the same testosterone concentration. Injection of pituitary fractions into the short photoperiod fish reduced fanning to the levels found under long photoperiods. Normal males under long photoperiod showed significantly higher fanning than any of the gonadectomized groups indicating that methyl testosterone in concentrations used did not fully replace the effects of the normal gonad. Exposure of males to a wide range of testosterone concentrations indicated that a relatively high concentration of testosterone was required for normal fanning. Low levels of fanning occurred after gonadectomy of fish in breeding condition in both "displacement" fanning and parental fanning stages, indicating the gonad was not required for performance of the fanning pattern as such but was required for fanning to reach levels approaching these found in normal fish. No evidence was found that prolactin initiates or maintains the parental fanning cycle. Testosterone however was necessary for normal fanning levels. / Science, Faculty of / Zoology, Department of / Graduate

A group of five goldfish, Carassius auratus, treated ten and sixteen days with a 1: 3,980,000 concentration of synthetic sodium thyroxine during the winter, had their oxygen consumption significantly raised. Five goldfish treated with .03 per cent thiourea for the same lengths of time during the same period had their oxygen consumption significantly depressed. Two series of similar treatments of three, seven, fourteen and twenty-one days duration throughout the summer did not statistically alter the oxygen consumption and ammonia excretion. Treatments with a 1: 1500,000 concentration of methyl testosterone for three, seven, fourteen and twenty-one days statistically elevated the oxygen consumption and ammonia excretion. The thiourea, synthetic sodium thyroxine and methyl testosterone treatments for three, seven, fourteen and twenty-one days did not appreciably alter the total lipid and moisture content of the goldfish tissue. These treatments do not appear to alter the oxygen carbon dioxide tension at death nor the length of time to asphyxiate the goldfish. / Science, Faculty of / Zoology, Department of / Graduate

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