RESUMO
The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.0 mg/kg) or vehicle (60.0 µL) and were submitted or not to swimming sessions (60 min, 5% body weight overload) for 4 weeks. Gastric emptying, intestinal transit, in vitro GI contractility, intestinal morphometry, and duodenal mucosal mast cells were evaluated in all experimental groups. ND treatment accelerated gastric emptying, slowed small intestine transit time, enhanced gastric carbachol-mediated reactivity, decreased crypt depth and villus height, reduced mucosal thickness, and increased the circular and longitudinal muscle layer thickness of the duodenum in sedentary rats. Moderate exercise accelerated intestinal transit time and reduced submucosa thickness. In vehicle-treated animals, a strong negative correlation was found between intestinal transit and mucosal mast cells, which was reversed by ND treatment. Combining ND treatment and swimming accelerated gastric emptying, increased duodenal cholinergic reactivity, inhibited the sodium nitroprusside relaxing response, increased the number of duodenal mast cells, decreased villus height, and increased the thickness of all muscle layers. ND changed the morphological and functional properties of the GI tract over time, with intense dysmotility, especially in sedentary animals, but moderate exercise seemed to have played a compensatory role in these harmful effects in the gut.
Assuntos
Anabolizantes , Duodeno , Motilidade Gastrointestinal , Decanoato de Nandrolona , Nandrolona , Condicionamento Físico Animal , Ratos Wistar , Animais , Masculino , Decanoato de Nandrolona/farmacologia , Duodeno/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Anabolizantes/farmacologia , Nandrolona/farmacologia , Nandrolona/análogos & derivados , Mastócitos/efeitos dos fármacos , Ratos , Natação , Esvaziamento Gástrico/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the initial impact of a combined oral contraceptive (COC) containing norgestimate (NGM) on female sexuality and on circulating androgen levels in users. MATERIALS AND METHODS: Six months modification in the McCoy Female Sexuality Questionnaire (MFSQ) and testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) serum levels in women starting a monophasic pill containing ethinyl-estradiol (EE) 35 µg and NGM 0.250 mg. RESULTS: The study was completed by 36 subjects. There was a significant increase in MFSQ during treatment (p < 0.0001) (and its domains with the exclusion of vaginal lubrication domain) with concomitant decreases in T (-4.45%, p < 0.0001) and DHEAS (-19.41%, p < 0.0001) serum levels. CONCLUSIONS: Contraception with EE/NGM was associated with a short term non-deteriorating effect on sexuality despite the evident decrease in androgen levels. Female sexuality during COC use is a complex topic and is not only linked with changes in serum androgen levels.
EE/NGM treatment has a short term non-deteriorating effect on sexuality despite the evident decrease in androgen serum levels.
Assuntos
Anticoncepcionais Orais Combinados , Etinilestradiol , Testosterona , Humanos , Feminino , Projetos Piloto , Etinilestradiol/farmacologia , Etinilestradiol/administração & dosagem , Adulto , Testosterona/sangue , Anticoncepcionais Orais Combinados/farmacologia , Sulfato de Desidroepiandrosterona/sangue , Androgênios/sangue , Sexualidade/efeitos dos fármacos , Nandrolona/análogos & derivados , Nandrolona/farmacologia , Inquéritos e Questionários , Adulto Jovem , Norgestrel/análogos & derivadosRESUMO
Caffeine and anabolic-androgenic steroids (AAS) are commonly used to improve muscle mass and athletic performance. Nandrolone Decanoate (ND) is one of the most abused AAS worldwide, leading to behavioral changes in both humans and rodents. Caffeine, the most widely consumed psychostimulant globally, is present in various thermogenic and gym supplements. Low and moderate doses of caffeine antagonize adenosine receptors and have been linked to improved memory and pain relief. We have previously demonstrated that consuming caffeine prevents the risk-taking behavior triggered by nandrolone. In this study, we aimed to investigate the long-term effects of ND and caffeine, either alone or in combination, on passive avoidance memory and nociception. We used the step-down and hot-plate tasks in male and female Lister Hooded rats. Our results confirmed the antinociceptive effect of caffeine and indicated that chronic administration of the ND-caffeine association promotes the evocation of aversive memory in female rats.
Assuntos
Aprendizagem da Esquiva , Cafeína , Memória , Decanoato de Nandrolona , Nociceptividade , Animais , Cafeína/farmacologia , Feminino , Masculino , Ratos , Nociceptividade/efeitos dos fármacos , Decanoato de Nandrolona/farmacologia , Memória/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Nandrolona/farmacologia , Nandrolona/análogos & derivados , Estimulantes do Sistema Nervoso Central/farmacologia , Anabolizantes/farmacologiaRESUMO
PURPOSE: This study examined the acute and long-term effects of nandrolone decanoate (ND) on fractional synthetic rates (FSR). METHODS: Male C57BL/6 mice were randomized into ND ( n = 20) or sham ( n = 20) groups. ND injections (10 g·kg -1 ·wk -1 ) started at 7 months of ages and continued for 6 wk. Ten animals from each group were randomly separated and examined 1 wk following drug cessation. The remaining animals were examined at 16 months of age. Animals were injected IP with 1.5 mL of deuterated water 24 h before euthanasia. The kidney, liver, heart, gastrocnemius, and soleus were extracted. Samples were analyzed for deuterated alanine enrichment in the bound protein and intracellular fraction by liquid chromatography tandem mass spectrometry to measure estimated FSR (fraction/day (F/D)) of mixed tissue. RESULTS: One-way ANOVA, with treatment and age as fixed factors, indicated that kidney FSR was greater ( P = 0.027) in ND (0.41 ± 0.02 F/D) than sham (0.36 ± 0.014F/D) and higher ( P = 0.003) in young (0.42 ± 0.2 F/D) than old (0.35 ± 0.01 F/D). Liver and heart FSR values were greater ( P ≤ 0.001) in young (0.79 ± 0.06 F/D and 0.13 ± 0.01 F/D, respectively) compared with old (0.40 ± 0.01 F/D and 0.09 ± 0.01 F/D, respectively), but not between ND and sham. Gastrocnemius FSR was ( P ≤ 0.001) greater in young (0.06 ± 0.01 F/D) compared with old (0.03 ± 0.002 F/D), and greater ( P = 0.006) in ND (0.05 ± 0.01 F/D) compared with sham (0.04 ± 0.003 F/D). Soleus FSR rates were greater ( P = 0.050) in young (0.13 ± 0.01 F/D) compared with old (0.11 ± 0.003 F/D), but not between ND (0.12 ± 0.01 F/D) and sham (0.12 ± 0.01 F/D). Old animals who had received ND displayed elevated FSR in the gastrocnemius ( P = 0.054) and soleus ( P = 0.024). CONCLUSIONS: ND use in young adult animals appeared to maintain long-term elevations in FSR in muscle during aging.
Assuntos
Envelhecimento , Fígado , Camundongos Endogâmicos C57BL , Proteínas Musculares , Músculo Esquelético , Animais , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Proteínas Musculares/biossíntese , Proteínas Musculares/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Decanoato de Nandrolona/farmacologia , Decanoato de Nandrolona/administração & dosagem , Rim/metabolismo , Rim/efeitos dos fármacos , Miocárdio/metabolismo , Camundongos , Androgênios/administração & dosagem , Androgênios/farmacologia , Distribuição Aleatória , Nandrolona/farmacologia , Nandrolona/administração & dosagem , Nandrolona/análogos & derivados , Anabolizantes/administração & dosagem , Anabolizantes/farmacologiaRESUMO
Long-term use of anabolic androgenic steroids (AAS) in supratherapeutic doses is associated with severe adverse effects, including physical, mental, and behavioral alterations. When used for recreational purposes several AAS are often combined, and in scientific studies of the physiological impact of AAS either a single compound or a cocktail of several steroids is often used. Because of this, steroid-specific effects have been difficult to define and are not fully elucidated. The present study used male Wistar rats to evaluate potential somatic and behavioral effects of three different AAS; the decanoate esters of nandrolone, testosterone, and trenbolone. The rats were exposed to 15 mg/kg of nandrolone decanoate, testosterone decanoate, or trenbolone decanoate every third day for 24 days. Body weight gain and organ weights (thymus, liver, kidney, testis, and heart) were measured together with the corticosterone plasma levels. Behavioral effects were studied in the novel object recognition-test (NOR-test) and the multivariate concentric square field-test (MCSF-test). The results conclude that nandrolone decanoate, but neither testosterone decanoate nor trenbolone decanoate, caused impaired recognition memory in the NOR-test, indicating an altered cognitive function. The behavioral profile and stress hormone level of the rats were not affected by the AAS treatments. Furthermore, the study revealed diverse AAS-induced somatic effects i.e., reduced body weight development and changes in organ weights. Of the three AAS included in the study, nandrolone decanoate was identified to cause the most prominent impact on the male rat, as it affected body weight development, the weights of multiple organs, and caused an impaired memory function.
Assuntos
Anabolizantes , Transtornos da Memória , Nandrolona , Ratos Wistar , Testosterona , Animais , Masculino , Testosterona/sangue , Testosterona/análogos & derivados , Ratos , Nandrolona/análogos & derivados , Nandrolona/farmacologia , Anabolizantes/efeitos adversos , Anabolizantes/farmacologia , Transtornos da Memória/induzido quimicamente , Tamanho do Órgão/efeitos dos fármacos , Acetato de Trembolona/farmacologia , Decanoato de Nandrolona/farmacologia , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Reconhecimento Psicológico/efeitos dos fármacosRESUMO
Male contraceptive development has included use of testosterone (T) with or without a progestin or the use of a single molecule such as progestogenic androgens (PA) for suppression of testicular T production. Expanding upon the vast amount of data accumulated from nortestosterone (NT), NT analogs, and their prodrugs, a new series of PA, the C7 methyl, and ethyl α-substituted T analogs 7α-Methyltestosterone (7α-MT) and 7α-Ethyltestosterone (7α-ET), respectively, were hypothesized and designed to have superior androgenic and progestogenic activities when compared with parent T. Results from androgen receptor and progesterone receptor competitive binding and transcriptional activation assays showed favorable activities for these T analogs. Additionally, 7α-MT and 7α-ET were shown to be active substrates for aromatase in vitro, mitigating a potential negative impact on bone mineral density with long-term use. In conjunction with this observation, the diminished metabolism of these T analogs by 5α-reductase may reduce potential concerns for prostatic growth. In the Hershberger in vivo rat bioassay, 7α-MT and 7α-ET showed superior androgenic and anabolic activities as compared with T. These C7 α-substituted T analogs also showed clear progestogenic activity in the McPhail bioassay which evaluated endometrial glandular arborization in a rabbit model. The discovery of aromatizable molecules with reduced metabolism by 5α-reductase that have androgenic, anabolic, and progestogenic properties indicates that the core and/or prodrugs of 7α-MT and 7α-ET are promising molecules for further development as male contraceptive PAs.
Assuntos
Anticoncepcionais Masculinos , Nandrolona , Pró-Fármacos , Masculino , Ratos , Coelhos , Animais , Humanos , Androgênios/farmacologia , Androgênios/metabolismo , Testosterona , Progestinas/farmacologia , Nandrolona/farmacologia , Nandrolona/metabolismo , Metiltestosterona , Anticoncepção , Anticoncepcionais Masculinos/farmacologiaRESUMO
PURPOSE: to compare the effects of Dienogest 2 mg (D) alone or combined with estrogens (D + ethinylestradiol 0.03 mg, D + EE; D + estradiol valerate 1-3 mg, D + EV) in terms of symptoms and endometriotic lesions variations. METHODS: This retrospective study included symptomatic patients in reproductive age with ultrasound diagnosis of ovarian endometriomas. Medical therapy for at least 12 months with D, D + EE or D + EV was required. Women were evaluated at baseline visit (V1) and after 6 (V2) and 12 months (V3) of therapy. RESULTS: 297 patients were enrolled (156 in the D group, 58 in the D + EE group, 83 in the D + EV group). Medical treatment leaded to a significant reduction in size of endometriomas after 12 months, with no differences between the three groups. When comparing D and D + EE/D + EV groups, a significant decrease of dysmenorrhea was detected in the D group than in D + EE/D + EV group. Conversely, the reduction of dysuria was more significative in the D + EE/D + EV groups rather than in the D group. Regarding tolerability, treatment associated side effects were reported by 16.2% patients. The most frequent one was uterine bleeding/spotting, significantly higher in the D + EV group. CONCLUSION: Dienogest alone or associated with estrogens (EE/EV) seems to be equally effective in reducing endometriotic lesions mean diameter. The reduction of dysmenorrhea was more significative when D was administered alone, while dysuria seems to improve more when D is associated with estrogens.
Assuntos
Endometriose , Nandrolona , Humanos , Feminino , Estrogênios/uso terapêutico , Estudos Retrospectivos , Endometriose/diagnóstico por imagem , Endometriose/tratamento farmacológico , Endometriose/complicações , Dismenorreia/complicações , Disuria/complicações , Disuria/tratamento farmacológico , Estradiol , Nandrolona/uso terapêutico , Nandrolona/farmacologiaRESUMO
Anabolic androgenic steroids are synthetic substances related to the male sex hormones (androgens). These agents promote the growth of skeletal muscle (anabolic effects) and the development of male sexual characteristics (androgenic effects). Anabolic steroids have been illegally used for many years as performance-enhancing drugs in human, equine, and canine sports and as growth promoters in livestock reared to provide meat for human consumption. The analytical challenge to developing effective means of control within these fields has been exacerbated by the reported endogenous nature of some of these steroids. Anabolic steroids have been employed extensively in equine practice over the past 50 years. Their usefulness is largely dependent on subjective opinions, as only minimal studies investigating pharmacodynamics have been carried out in horses. Therefore, their use will vary markedly between practitioners depending on their personal experiences and pressures by trainers to use them. They form part of rational therapy in a variety of conditions. In addition to their use for increasing muscle mass, they are used to varying extents in the raising of yearlings and in the training and racing of horses with the view of improving performance. The use of these agents is prohibited in the horseracing industry by the Association of Racing Commissioners International (ARCI), International Federation of Horseracing Authorities (IFHA), and Fédération Equestre Internationale (FEI).
Assuntos
Anabolizantes , Dopagem Esportivo , Nandrolona , Cavalos , Animais , Masculino , Cães , Humanos , Esteróides Androgênicos Anabolizantes , Nandrolona/farmacologia , Testosterona , Androgênios/farmacologia , Esteroides/química , Anabolizantes/farmacologia , Anabolizantes/químicaRESUMO
PURPOSE: The aim of this study was to compare the effects of Dienogest and medroxyprogesterone acetate (MPA) on the recurrence of endometriosis lesions and clinical symptoms in women undergoing laparoscopic surgery. METHODS: This single center clinical trial was conducted among 106 women with endometriosis undergoing laparoscopic surgery who candidate receiving post-surgery hormone therapy. Participants were allocated to two groups. The first group received Dienogest pills (2 mg) daily for the first three months and then cyclic for three months afterward. The second group received MPA pills twice daily (10 mg) for three months and then cyclic for the next three months. Six months after the intervention, the rate of endometriosis recurrence, the size of endometriosis lesions and pelvic pain were assess and compared between two groups. RESULTS: Finally, data were evaluated based on 48 and 53 women in the Dienogest and MPA groups, respectively. After 6 months follow-up assessments the pelvic pain score was significantly lower in Dienogest group than MPA group (P < 0.001). There was not statistically difference between two groups in terms of recurrence rate of endometriosis (P = 0.4). Although the size of endometriosis cyst recurrence was smaller in Dienogest group compared to MPA group (P = 0.02). CONCLUSIONS: The findings showed that Dienogest treatment has better effect in reducing pelvic pain and the mean size of the recurrent endometriosis lesions after endometriosis laparoscopic surgery when compared to MPA treatment. Although the recurrent rate of endometriosis was similar between these treatments.
Assuntos
Endometriose , Laparoscopia , Nandrolona , Feminino , Humanos , Endometriose/complicações , Endometriose/tratamento farmacológico , Endometriose/cirurgia , Acetato de Medroxiprogesterona/uso terapêutico , Nandrolona/uso terapêutico , Nandrolona/farmacologia , Dor Pélvica/tratamento farmacológico , Dor Pélvica/etiologia , Dor Pélvica/cirurgiaRESUMO
Endometriosis affects up to 10% of women of reproductive age, causing dysmenorrhea, chronic pelvic pain, and infertility. The current key drug for endometriosis is dienogest, a progestin with high specificity for the progesterone receptor. To reveal the direct anti-endometriotic effect of dienogest on ovarian endometriotic cells, we investigated the genome-wide gene expression profiles of ovarian endometriotic stromal cells with (Dienogest group) or without dienogest treatment (Control group) and compared the groups' gene expression profiles. We performed a gene ontology (GO) analysis and Ingenuity pathway analysis using these data. To validate the microarray data, we performed real-time RT-PCRs and immunohistochemistry for the differentially expressed genes between the two groups. Of 647 genes differentially expressed between the two groups, 314 genes were upregulated and 333 were downregulated in the Dienogest group versus the Control group. The GO analysis showed that the regulation of macrophage chemotaxis, the collagen catabolic process, and the proteoglycan biosynthetic process are the main biological processes closely associated with the differentially expressed genes. We identified 20 canonical pathways that were most significantly differentially expressed in the Dienogest group versus the Control group. We observed that matrix metalloproteinases (MMPs) are the genes in these pathways that are most closely associated with dienogest treatment. Of components involved in the regulation of macrophage chemotaxis, colony-stimulating factor 1 and macrophage-stimulating 1 are potential upstream regulators of MMPs and were observed herein to be suppressed by dienogest. Our results suggest that dienogest may thus exert its anti-endometriotic effect by directly suppressing MMPs.
Assuntos
Endometriose , Nandrolona , Humanos , Feminino , Endometriose/tratamento farmacológico , Endometriose/genética , Endometriose/complicações , Progestinas/farmacologia , Nandrolona/farmacologia , Nandrolona/uso terapêutico , Perfilação da Expressão Gênica , Células Estromais/metabolismoRESUMO
Nandrolone, an anabolic androgenic steroid, is included in the prohibited list of the World Anti-Doping Agency. Drugs of abuse activate brain dopamine neurons and nandrolone has been suspected of inducing dependence. Accordingly, possible critical periods for the effects of nandrolone on muscular strength and dopaminergic activity have been investigated, including the effects of chronically administered nandrolone alone and on morphine-induced increases in dopamine efflux in the nucleus accumbens. Six- or 10-week-old male Sprague-Dawley rats were used. Treatment with nandrolone was initiated in adolescent (6-week-old) and young adult (10-week-old) rats. Nandrolone (5.0 mg/kg s.c.) or sesame oil vehicle was given once daily, on six consecutive days per week, for 3 weeks and then once per day for 4 consecutive days. Nandrolone enhanced the developmental increase in grip strength of 6- but not 10-week-old rats, without altering the developmental increase in body weight of either age group. Using in vivo microdialysis in freely moving 6-week-old rats given nandrolone for 4 weeks, basal accumbal dopamine efflux was unaltered, while the increase in dopamine efflux induced by acute administration of morphine (1.0 mg/kg s.c.) was reduced. The present study provides in vivo evidence that adolescence constitutes a critical period during which repeated administration of nandrolone enhances increases in muscular strength without influencing increases in body weight. Though repeated administration of nandrolone during this period of adolescence did not stimulate in vivo mesolimbic dopaminergic activity, it disrupted stimulation by an opioid, the drug class that is most commonly coabused with nandrolone.
Assuntos
Dopamina , Nandrolona , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Nandrolona/farmacologia , Morfina/farmacologia , Núcleo AccumbensRESUMO
This study examined the effect of 6 weeks of supraphysiological nandrolone decanoate (ND) administration in adult mice (7 months) on cognitive function and neuroinflammation during aging. Male C57BL/6 mice were randomized into ND (10 mg·kg-1·wk-1) or control (CTL) groups. Half of the mice were tested at a young (Y) age (ND-Y and CTL-Y), 1 week following final ND administration, while the remaining mice were tested at 16 months (O) (ND-O and CTL-O). Learning and memory were better in young mice compared to older mice, regardless of treatment. ND-O displayed decreased anxiety as compared to all other groups. TNFα and IL1ß expression were higher in older mice, regardless of treatment. ND administration in young mice appeared to attenuate the neuroinflammatory response in aging mice as evidenced by decreased COX2, IL-4 and increased IL-10 expression in ND-O compared to CTL-O. BDNF AR and ER expression increased in ND-O compared to CTL-O. Results of the study indicated that supraphysiological ND administration had no negative effect on learning and memory but may attenuate anxiety in older mice. In addition, ND administration in young adult mice may attenuate the inflammatory response during aging, which may be related to elevations in both AR and ER expression.
Assuntos
Anabolizantes , Nandrolona , Masculino , Camundongos , Animais , Decanoato de Nandrolona , Nandrolona/farmacologia , Anabolizantes/farmacologia , Fatores de Crescimento Neural , Camundongos Endogâmicos C57BLRESUMO
The anabolic androgenic steroids (AAS) are natural compounds that are precursors or derivatives of testosterone and, as a consequence of indiscriminate use, cause irreversible neuronal effects. For this study, 70 brain samples were used from male Wistar rats, separated into 14 groups, divided into: control, sedentary, and exercise groups; in the concentrations: 5 mg, 10 mg, and 15 mg. Two different AAS were used: Testosterone Cypionate (TC) and Nandrolone Decanoate (ND). The encephali followed all the conventional histological procedures, for further analysis of the estimates of neuron bodies of the Locus coeruleus; also being carried out the techniques of the Tunnel Assay and Von Kossa staining. The results obtained show significant values different from the control group: Testosterone Cypionate (TCS): 5 mg (25,00 ± 4,47); 10 mg (23,67 ± 4,45) and 15 mg (21,93 ± 5,65), as well as for Nandrolone Decanoate (ND) in the doses: 5 mg (23,40 ± 3,81); 10 mg (22,80 ± 3,80) and 15 mg (22,80 ± 4,54) being the values of the control group (CGS) 34,27 ± 6,06. For the groups that exercised, the values were: TCT 5 mg 20,87 ± 3,23; TCT 10 mg 21,93 ± 4,91 and TCT 15 mg 21,47 ± 4,36 while, the Nandrolone Decanoate (ND) groups, in the different doses were: NDT 5 mg 21,53 ± 4,34; NDT 10 mg 23,53 ± 1,68 and NDT 15 mg 23,40 ± 2,20, also expressing significant values different from the control group. When comparing the sedentary control group with the animals that exercised, a statistically significant difference was observed being: CGS 34,27 ± 6,06; TCT 5 mg; 20,87 ± 3,23; NDT 5 mg 21,53 ± 4,34; TCT 10 mg 21,93 ± 4,91; NDT 10 mg 23,53 ± 1,68; TCT 15 mg 21,47 ± 4,36 and NDT 15 mg 23,40 ± 2,20. The results of this study, point out that both steroids drastically reduce neuronal density in the Locus coeruleus area inferring that, the possible cause of neuronal death is necrosis, caused by intracellular calcium imbalance.
Assuntos
Anabolizantes , Nandrolona , Congêneres da Testosterona , Animais , Masculino , Ratos , Anabolizantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Nandrolona/farmacologia , Decanoato de Nandrolona , Ratos Wistar , Esteroides , Congêneres da Testosterona/efeitos adversos , Congêneres da Testosterona/farmacologia , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/etiologiaRESUMO
INTRODUCTION: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E2 ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin. MATERIAL AND METHODS: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover). CLINICAL TRIAL REGISTRATION: NCT02352090. RESULTS: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers. CONCLUSIONS: Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives.
Assuntos
Anticoncepcionais Orais Combinados , Nandrolona , Adolescente , Adulto , Anticoncepcionais Orais Combinados/farmacologia , Estradiol , Estrogênios , Etinilestradiol/farmacologia , Feminino , Fibrina , Humanos , Levanogestrel , Nandrolona/farmacologia , Progestinas , Trombina , Tromboplastina , Adulto JovemRESUMO
Anabolic androgenic steroids (AAS) are frequently used to improve physical appearance and strength. AAS are known to affect muscle growth, but many AAS-users also experience psychiatric and behavioral changes after long-term use. The AAS-induced effects on the brain seem to depend on the type of steroid used, but the rationale behind the observed effect is still not clear. The present study investigated and compared the impact of nandrolone decanoate and testosterone undecanoate on body weight gain, levels of stress hormones, brain gene expression, and behavioral profiles in the male rat. The behavioral profile was determined using the multivariate concentric squared field test (MCSF-test). Blood plasma and brains were collected for further analysis using ELISA and qPCR. Nandrolone decanoate caused a reduction in body weight gain in comparison with both testosterone undecanoate and control. Rats receiving nandrolone decanoate also demonstrated decreased general activity in the MCSF. In addition, nandrolone decanoate reduced the plasma levels of ACTH in comparison with the control and increased the levels of corticosterone in comparison with testosterone undecanoate. The qPCR analysis revealed brain region-dependent changes in mRNA expression, where the hypothalamus was identified as the region most affected by the AAS. Alterations in neurotransmitter systems and stress hormones may contribute to the changes in behavior detected in the MCSF. In conclusion, both AAS affect the male rat, although, nandrolone decanoate has more pronounced impact on the physiological and the behavioral parameters measured.
Assuntos
Anabolizantes , Nandrolona , Anabolizantes/farmacologia , Animais , Peso Corporal , Masculino , Nandrolona/farmacologia , Decanoato de Nandrolona , Neurotransmissores/farmacologia , Ratos , Testosterona/análogos & derivados , Testosterona/farmacologiaRESUMO
Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14th day, brain 18FDG-microPET scans were performed. Hypothalamic pAMPKT172/AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18FDG uptake. We found that ND increased the pAMPKT172/AMPK ratio in both adult and aged mice but increased 18FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.
Assuntos
Anabolizantes , Nandrolona , Proteínas Quinases Ativadas por AMP/metabolismo , Anabolizantes/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Suplementos Nutricionais , Fluordesoxiglucose F18 , Glucose/metabolismo , Camundongos , Nandrolona/metabolismo , Nandrolona/farmacologia , Decanoato de Nandrolona , Tomografia por Emissão de PósitronsRESUMO
CONTEXT: Limited studies have compared the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. OBJECTIVE: To compare estradiol valerate (EV)â +â dienogest (DNG), EEâ +â DNG, and DNG alone (active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, anti-Müllerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the free androgen index (FAI). METHODS: This spin-off study from a randomized trial enrolled 59 healthy, 18 to 35-year-old ovulatory women, outpatients at Helsinki and Oulu University Hospitals, Finland, who were randomized to EV 2 mgâ +â DNG 2-3 mg (nâ =â 20); EE 0.03 mgâ +â DNG 2 mg (nâ =â 20); and DNG 2 mg (nâ =â 19) for 9 weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Age and BMI were comparable between groups; 3 women discontinued. RESULTS: EVâ +â DNG suppressed FSH by -27% (-51% to -3%) (median [95% CI]) vs EEâ +â DNG, -64% (-78 to -51), Pâ =â 0.04, but AMH levels decreased similarly by -9% (-18 to -0.1) vs -13% (-28 to 0.2), Pâ =â 0.38, respectively. EVâ +â DNG increased SHBG levels by 56% (30% to 82%) and EEâ +â DNG by 385% (313% to 423%), Pâ <â 0.001. Total testosterone decreased by 16% (-27% to -5%) in the EVâ +â DNG group but it did not decrease in the EEâ +â DNG group, whereas the FAI decreased by -39% (-54% to -25%) vs -72% (-78% to -67%), Pâ <â 0.001. DNG alone did not induce changes in any of these parameters. CONCLUSION: Compared with EEâ +â DNG, treatment with EVâ +â DNG resulted in milder pituitary downregulation and reduced induction of hepatic SHBG synthesis-potentially carrying more beneficial health effects.
Assuntos
Nandrolona , Doenças da Hipófise , Adolescente , Adulto , Anticoncepcionais Orais Combinados/farmacologia , Estradiol/farmacologia , Etinilestradiol/farmacologia , Feminino , Hormônio Foliculoestimulante , Humanos , Nandrolona/farmacologia , Ovário , Adulto JovemRESUMO
Aging hinders the effectiveness of regenerative medicine strategies targeting the repair of volumetric muscle loss (VML) injury. Anabolic steroids have been shown to improve several factors which contribute to the age-related decline in muscle's regenerative capacity. In this study, the impact of exogenous nandrolone decanoate (ND) administration on the effectiveness of a VML regenerative repair strategy was explored using an aged animal model. Unilateral tibialis anterior VML injuries were repaired in 18-month-aged animal models (male Fischer 344 rat) using decellularized human skeletal muscle scaffolds supplemented with autologous minced muscle. The contralateral limb was left untreated/uninjured. Following repair, ND(+) or a carrier control (ND-) was delivered via weekly injection for a period of 8 weeks. At 8 weeks, muscle isometric torque, gene expression, and tissue structure were assessed. ND(+) treatment did not improve contractile torque recovery following VML repair when compared to carrier only ND(-) injection controls. Peak isometric torque in the ND(+) VML repair group remained significantly below contralateral uninjured control values (4.69 ± 1.18vs. 7.46 ± 1.53 N mm/kg) and was statistically indistinguishable from carrier only ND(-) VML repair controls (4.47 ± 1.18 N mm/kg). Gene expression for key myogenic genes (Pax7, MyoD, MyoG, IGF-1) were not significantly elevated in response to ND injection, suggesting continued age related myogenic impairment even in the presence of ND(+) treatment. ND injection did reduce the histological appearance of fibrosis at the site of VML repair, and increased expression of the collagen III gene, suggesting some positive effects on repair site matrix regulation. Overall, the results presented in this study suggest that a decline in regenerative capacity with aging may present an obstacle to regenerative medicine strategies targeting VML injury and that the delivery of anabolic stimuli via ND administration was unable to overcome this decline.
Assuntos
Nandrolona , Regeneração , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Masculino , Músculo Esquelético/fisiologia , Nandrolona/farmacologia , RatosRESUMO
OBJECTIVES: Given the cardiac pathological remodeling following to anabolic androgenic steroids (AASs) consumption, we examined the effect of chronic administration of nandrolone decanoate with high-intensity endurance exercise on the left ventricular hypertrophy index, levels of hydroxyproline, tumor necrosis factor-alpha (TNF-α), adiponectin (APN) and its receptors (AdipoR1 and AdipoR2) expression in rats' hearts. METHODS: The male Wistar rats randomly divided to six groups included the control (CTL), exercise (Ex), nandrolone (Nan), vehicle (Arach), trained vehicle (Ex + Arach), and trained nandrolone (Ex + Nan) groups that were treated for eight weeks. RESULTS: Nandrolone consumption significantly enhanced the hypertrophy index (p<0.05) and exercise intensified this effect. It also increased the level of cardiac hydroxyproline (p<0.001), however exercise completely masked this effect. The values of TNF-α protein and AdipoR1 protein significantly increased in trained nandrolone-treated (Ex + Nan) group in comparison with CTL group (p<0.05), however, did not show significant alteration in Nan or Ex groups. High-intensity endurance exercise significantly enhanced the AdipoR2 protein (p<0.05), but, co-administration of nandrolone with exercise prevented this effect. The mRNA expression of AdipoR1 significantly reduced in the animals that received nandrolone for eight weeks and exercise recovered this effect (p<0.001). CONCLUSIONS: Despite an additive effect of high-intensity endurance exercise plus nandrolone on TNF-α level, their effects on hydroxyproline and APN receptors expression is incompatible in heart of rat. It is suggests a part of beneficial regulatory role of endurance exercise against nandrolone induced heart remodeling may apply through modulation of APN system.