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2.
Eur J Obstet Gynecol Reprod Biol ; 294: 217-221, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301500

RESUMO

OBJECTIVE: Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation. STUDY DESIGN: STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation. RESULT: STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs. CONCLUSION: Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.


Assuntos
Endometriose , Nandrolona/análogos & derivados , Feminino , Humanos , Endometriose/genética , Metaloproteinase 2 da Matriz , Fator de Transcrição STAT3/metabolismo , Interleucina-6/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Antígeno Nuclear de Célula em Proliferação/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Células Estromais/metabolismo , Endométrio/metabolismo
3.
J Gynecol Obstet Hum Reprod ; 53(3): 102744, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346495

RESUMO

OBJECTIVE: NOD-like receptor pyrin domain-containing 3 (NLRP3) is a cytosolic multi-protein complex that induces inflammation and is negatively regulated by progesterone. Previous researches have reported abnormal induction of reactive oxygen species (ROS) and progesterone resistance in endometriosis (EM). Since progesterone regulates ROS level and, consequently, inflammation, our objective is to investigate whether dienogest (DNG) regulates NLRP3 and whether the regulation of NLRP3 inflammasome by DNG in the blood plasma of patients with EM can affect oxidant and antioxidant markers. METHODS: Plasma samples were obtained from control and EM patients experiencing pain symptoms to measure the level of NLRP3, oxidants, and antioxidants. Subsequently, these patients were given oral DNG 2 mg/day for six months for drug treatment. After six months, plasma samples were collected from the patients for re-examination. RESULTS: The findings indicate that DNG reduced NLRP3 concentration and oxidant production while increasing antioxidant production in blood plasma. By reducing NLRP3, DNG was able to alleviate inflammation and pain caused by inflammation in EM patients. CONCLUSION: In conclusion, the use of DNG in EM patients resulted in a decrease in NLRP3 concentration in the patient's plasma. Furthermore, this effect was enhanced by balancing oxidant/antioxidant levels, which may contribute to reducing inflammation associated with EM.


Assuntos
Antioxidantes , Endometriose , Nandrolona/análogos & derivados , Feminino , Humanos , Oxidantes , Endometriose/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Progesterona , Espécies Reativas de Oxigênio , Dor , Inflamação , Plasma
4.
Eur J Obstet Gynecol Reprod Biol ; 295: 67-74, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340593

RESUMO

OBJECTIVE: One serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker. STUDY DESIGN: This was a prospective cohort study. Female patients aged 20 - 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P < 0.05 was considered statistically significant. RESULTS: 64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies. CONCLUSION: The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.


Assuntos
Endometriose , Nandrolona , Nandrolona/análogos & derivados , Humanos , Feminino , Anticoncepcionais Orais Combinados/efeitos adversos , Endometriose/tratamento farmacológico , Estudos Prospectivos , Nandrolona/efeitos adversos
5.
Obstet Gynecol ; 143(3): 431-434, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38227942

RESUMO

This pooled analysis compared the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) containing estradiol (E2) valerate-dienogest with those containing ethinyl E2-levonorgestrel. Data were retrieved from two large, prospective, observational cohort studies. Propensity score subclassification was applied to balance baseline parameters between the COC user cohorts. Crude and adjusted hazard ratios (HRs) were calculated based on the extended Cox model. The pooled data set included 11,616 E2 valerate-dienogest users and 18,681 ethinyl E2-levonorgestrel users, contributing 17,932 and 29,140 women-years of observation, respectively. A significantly decreased VTE risk in E2 valerate-dienogest COCs compared with ethinyl E2-levonorgestrel COCs was observed (propensity score-stratified HR 0.46, 95% CI, 0.22-0.98). This pooled analysis expands data from a previous postauthorization safety study and provides valuable real-world safety information on the relative safety of current COCs.


Assuntos
Anticoncepcionais Orais Combinados , Estradiol/análogos & derivados , Nandrolona/análogos & derivados , Tromboembolia Venosa , Feminino , Humanos , Anticoncepcionais Orais Combinados/efeitos adversos , Levanogestrel , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologia , Estudos Prospectivos , Etinilestradiol/efeitos adversos , Estradiol/efeitos adversos , Valeratos , Combinação de Medicamentos
6.
Arch Gynecol Obstet ; 309(2): 589-597, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38019280

RESUMO

PURPOSE: To evaluate the efficacy and long-term safety (up to 108 months) of treatment with Dienogest in patients with endometriosis. METHODS: Patients with chronic pelvic pain endometriosis-related were enrolled in this observational study from June 2012 to July 2021. The patients enrolled took Dienogest 2 mg as a single daily administration. Group B of long-term therapy patients (over 15 months) were compared with group A of short-term therapy patients (0-15 months). The effects of the drug on pain variation were assessed using the VAS scale and endometriomas dimensions through ultrasonographic evaluation. Furthermore, has been valuated the appearance of side effects and the effect of the drug on bone metabolism by performing MOC every 24 months in group B. RESULTS: 157 patients were enrolled. The mean size of the major endometrioma progressively decreased from 33.2 mm (29.4-36.9) at T0 to 7 mm (0-15.8) after 108 months of treatment. We found a significant improvement in dysmenorrhea, dyspareunia, dyschezia and non-cyclic pelvic pain. As for the side effects, both groups complained menstrual alterations present in 22.9%. In 27.6% of group B, osteopenia was found. Group B had a higher percentage statistically significant of side effects such as headaches, weight gain and libido reduction compared to group A. 2 CONCLUSION: Long-term therapy with Dienogest has proven effective in controlling the symptoms of the disease and reducing the size of endometriomas, with an increase in the positive effects related to the duration of the intake and in the absence of serious adverse events. Study approved by the "Palermo 2" Ethics Committee on July 2, 2012 No. 16.


Assuntos
Dor Crônica , Endometriose , Nandrolona , Feminino , Humanos , Endometriose/complicações , Endometriose/tratamento farmacológico , Endometriose/diagnóstico , Dor Pélvica/tratamento farmacológico , Dor Pélvica/etiologia , Dismenorreia/complicações , Nandrolona/efeitos adversos , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Resultado do Tratamento
7.
Orthop Traumatol Surg Res ; 110(1): 103723, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37879533

RESUMO

BACKGROUND: Muscle fatty degeneration following rotator cuff tears has been unequivocally associated with poorer functional outcomes and increased risk for retear following rotator cuff repair. Promising results have emerged from animal studies, with the implementation of various interventions for biologic inhibition of this fatty muscle degeneration. The lack of high quality randomized human evidence on this topic, increases the impact of pooled results from animal literature. The aim of the present study was to systematically review the available published literature for animal studies evaluating the ability of several interventions used to mitigate muscle fatty degeneration following the repair of massive rotator cuff tears. PATIENTS AND METHODS: A comprehensive search was conducted on Pubmed, Scopus and Google Scholar, covering the period from conception until 16th April 2022. Datasets were stratified based on the type of intervention performed. SYRCLE risk of bias instrument was implemented for quality assessment of the included studies. RESULTS: Rotator cuff repair augmentation with Adipose derived stem cells (ADSC's), Mesenchymal stem cells (MSC's) and Nandrolone was effective against fatty infiltration, but less effective against muscle atrophy. More beneficial effect was shown by the utilization of Beige adipose tissue - Fibroadipogenic progenitors (BAT-FAP) stimulation, using either Amibregon or BAT-FAPs transplantation. Both provided good results in mitigating muscle atrophy, fatty infiltration and fibrosis. DISCUSSION: ADSC's, MSC's, Nandrolone and BAT-FAP stimulation may have a role in mitigating muscle fatty degeneration following rotator cuff tears. Large scale human studies are required to further elucidate their role in the clinical setting. LEVEL OF EVIDENCE: V; systematic review of pre-clinical studies.


Assuntos
Nandrolona , Lesões do Manguito Rotador , Animais , Tecido Adiposo/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/prevenção & controle , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/complicações
8.
Clin Pharmacol Drug Dev ; 13(2): 140-145, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37743573

RESUMO

This trial was a randomized, open-label, single-dose, 2-treatment, 2-period, crossover study to evaluate the pharmacokinetic (PK) profile, bioequivalence, and safety of test formulation and reference formulation of 2-mg dienogest tablets in healthy Chinese participants. Eligible participants were randomly administered a single 2-mg dose of either the test formulation or the reference formulation orally under fed conditions, followed by a 1-week washout period and the administration of the other formulation. Samples of blood were collected until 48 hours following administration. The main PK parameters were calculated using noncompartmental analysis techniques. The main PK parameters included maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable concentration, and AUC from time zero to infinity. The bioequivalence of test and reference dienogest tablets was determined if the 90% confidence intervals of the geometric mean ratio of the test to reference formulations were within the predefined range of 80%-125%. The safety assessment included incidence of adverse events and serious adverse events and others. Twenty-four healthy Chinese participants were enrolled in this trial. The geometric mean ratios of maximum plasma concentration, AUC from time zero to the last quantifiable concentration, and AUC from time zero to infinity between the 2 formulations, and corresponding 90% confidence intervals, all fell within the range of 80%-125% under fed conditions. The test and reference dienogest tablets were well tolerated, and no severe adverse events were reported in the trial. It was shown that the test and the reference dienogest tablets were bioequivalent and well tolerated under fed conditions in healthy Chinese female participants.


Assuntos
Nandrolona/análogos & derivados , Equivalência Terapêutica , Humanos , Feminino , Disponibilidade Biológica , Estudos Cross-Over , China
9.
Molecules ; 28(21)2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37959848

RESUMO

Estradiol methyl ether (EDME) has recently been described by us as a very potent and subtype-specific inhibitor of the lysosomal cation channel TRPML1. Following the principle of bioisosteres, we worked out efficient synthetic approaches to ring-A aza-analogs of EDME, namely a methoxypyridine and a methoxypyrimidine analog. Both target compounds were obtained in good overall yields in six and eight steps starting from 19-nortestosterone via the oxidative cleavage of ring A followed over several intermediates and with the use of well-selected protective groups by re-cyclization to provide the desired hetero-analogs. The methoxypyridine analog largely retained its TRPML1-inhibitory activity, whereas the methoxypyrimidine analog significantly lost activity.


Assuntos
Nandrolona , Canais de Potencial de Receptor Transitório , Estradiol/farmacologia , Lisossomos
10.
Medicina (Kaunas) ; 59(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38003989

RESUMO

Background and Objectives: Nandrolone decanoate (ND) is the most widely used among the anabolic androgenic steroids (AAS), synthetic substances derived from testosterone, to improve muscular and health gains associated with exercises. The AAS leads to physical performance enhancement and presents anti-aging properties, but its abuse is associated with several adverse effects. Supraphysiological doses of AAS with or without physical exercise can cause morphological and functional alterations in neuromuscular interactions. This study aims to investigate the effects of ND supraphysiological doses in neuromuscular interactions, focusing on the soleus muscle and its neuromuscular junctions (NMJs) in rats, associated or not with physical exercise. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: sedentary and exercised groups, with or without ND at the dose of 10 mg/kg/week. The animals were treated for eight weeks, with intramuscular injections, and the soleus muscle was collected for morphological analyses. Results: The supraphysiological doses of ND in the sedentary group caused muscle degeneration, evidenced by splitting fibers, clusters of small fibers, irregular myofibrils, altered sarcomeres, an increase in collagen deposition and in the number of type I muscle fibers (slow-twitch) and central nuclei, as well as a decrease in fibers with peripheral nuclei. On the other hand, in the ND exercise group, there was an increase in the NMJs diameter with scattering of its acetylcholine receptors, although no major morphological changes were found in the skeletal muscle. Thus, the alterations caused by ND in sedentary rats were partially reversed by physical exercise. Conclusions: The supraphysiological ND exposure in the sedentary rats promoted an increase in muscle oxidative pattern and adverse morphological alterations in skeletal muscle, resulting from damage or post-injury regeneration. In the ND-exercised rats, no major morphological changes were found. Thus, the physical exercise partially reversed the alterations caused by ND in sedentary rats.


Assuntos
Anabolizantes , Nandrolona , Ratos , Masculino , Animais , Decanoato de Nandrolona/farmacologia , Nandrolona/efeitos adversos , Anabolizantes/efeitos adversos , Ratos Wistar , Ratos Sprague-Dawley , Músculo Esquelético/fisiologia , Junção Neuromuscular
11.
Biol Reprod ; 109(6): 851-863, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37669128

RESUMO

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/farmacologia
12.
J Immunol Methods ; 522: 113572, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37774776

RESUMO

In this study, we have developed bridge heterologous ELISA for the detection of 17α- Methyltestosterone by incorporating aromatic spacers between 17α-Methyltestosterone-3-Carboxymethyloxime and Horseradish peroxidase label through N-hydroxysuccinimide mediated carbodiimide reaction method. The immunogen 17α-Methyltestosterone-3-Carboxymethyloxime-Bovine serum albumin used to generate the antibody was also prepared by the N-hydroxysuccinimide mediated carbodiimide reaction without using any spacer. We have studied the impact of bridge/aromatic spacers on functional parameters i.e. sensitivity, affinity and ED50 of the bridge heterologous assay and compared it with homologous assay. The five combinations of bridge heterologous assay using 17α-Methyl testosterone-3-CMO-BSA antiserum and 17α-MT-3-CMO-4,4'-Diaminodiphenyl sulphide-HRP, 17α MT-3-CMO-4,4'-Oxydianiline-HRP, 17α-MT-3-CMO-Benzidine-HRP, 17α- MT-3-CMO-p-Phenylenediamine-HRP and 17α-MT-3-CMO-Dapson-HRP enzyme conjugates were evaluated. Out of these five combinations, the combination 17α-MT-3-CMO-BSA with 17α-MT-3-CMO-Benzidine-HRP showed the best results. Sensitivity, affinity and ED50 were improved and found to be 0.02 ng/mL, 0.086 × 10-8 L/mol and 2.95 ng/mL than homologous assay where Sensitivity, affinity and ED50 were 0.11 ng/mL, 0.02 × 10-8 L/mol and 5.78 ng/mL respectively. The cross-reactivity for this bridge heterologous assay combination was seen with only 4 steroids (6-hydrotestosterone- 6%, Testosterone-5.14%, Danazol-0.9% and Nandrolone-0.85%) instead of eight steroids (6-hydrotestosterone-43.75%, Testosterone-38.3%, Danazol-25.14%, Androstenediol-19.16%, Nandrolone-19%, Metandienone-5%, Androstenedione-3.52%, and 17α dimethyltestosterone-2%) as in homologous assay out of 59 structurally related steroids. Thus, the results of this study conclude that the incorporation of aromatic spacer (bridge) in enzyme conjugate has a crucial role in improving sensitivity, specificity, ED50 and affinity of the developed assay. The assay was then studied for parameters such as recovery (97.4%-108.6%), precision (Inter and Intra-assay coefficient of variation <10%), correlation coefficient (R2 = 0.96) by comparing with the commercial kit and validated by measuring levels of 17α- methyltestosterone in rat serum after administering them.


Assuntos
Metiltestosterona , Nandrolona , Animais , Ratos , Danazol , Ensaio de Imunoadsorção Enzimática/métodos , Antígenos , Esteroides , Testosterona , Benzidinas , Carbodi-Imidas
13.
Clin Ther ; 45(10): 973-976, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37599165

RESUMO

PURPOSE: The goal of this study was to examine the efficacy and safety of the levonorgestrel intrauterine system (LNG-IUS) versus dienogest (DNG) in female subjects with symptomatic uterine adenomyosis. METHODS: This study enrolled 117 women with symptomatic adenomyosis who visited our hospital from May 1, 2019, to June 30, 2022. Participants were randomized to either the LNG-IUS group (n = 48) or the DNG group (n = 79) in an as-controlled clinical trial for 36 months. Visual analog scale (VAS) scores, uterine volume, endometrial thickness, serum carcinoma antigen 125 level, estradiol, follicle-stimulating hormone, luteinizing hormone, and side effects were assessed to compare the efficacy of LNG-IUS and DNG. FINDINGS: The VAS pain score was significantly decreased in both groups after 3 months of treatment. Three months later, patients receiving DNG reported significantly lower VAS scores compared with those treated with LNG- IUS (P < 0.05). Compared with LNG-IUS, DNG effectively controlled uterine volume growth after 12 months of treatment but neither significantly reduced uterine volume. During the treatment period, endometrial thickness in both groups was maintained at 0.4 to 0.7 cm. IMPLICATIONS: Both DNG and LNG-IUS significantly improved adenomyosis-associated pain after 3 months of treatment. Compared with LNG-IUS, DNG was shown to continuously relieve the symptoms of pain and effectively control the growth of uterine volume.


Assuntos
Adenomiose , Nandrolona , Feminino , Humanos , Levanogestrel/efeitos adversos , Adenomiose/tratamento farmacológico , Adenomiose/induzido quimicamente , Adenomiose/complicações , Nandrolona/efeitos adversos , Dor/tratamento farmacológico
14.
Arch Gynecol Obstet ; 308(4): 1341-1349, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37433947

RESUMO

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/farmacologia
15.
J Vet Pharmacol Ther ; 46(4): 201-217, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37264491

RESUMO

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 , Doping nos Esportes , Nandrolona , Cavalos , Animais , Masculino , Cães , Humanos , Esteróides Androgênicos Anabolizantes , Nandrolona/farmacologia , Testosterona , Androgênios/farmacologia , Esteroides/química , Anabolizantes/farmacologia , Anabolizantes/química
16.
Eur J Contracept Reprod Health Care ; 28(3): 198-204, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37132337

RESUMO

OBJECTIVE: Primary aim of this study was to investigate endometriosis characteristics of patients with psychiatric conditions or depression. The secondary aim was to study tolerability of dienogest in this context. METHODS: This observational case-control study included endometriosis data from patients visiting our clinic from 2015-2021. We collected information from patient charts and in phone interviews based on a structured survey. Patients with surgical confirmed endometriosis were included. RESULTS: 344 patients fulfilled the inclusion criteria: n = 255 no psychiatric disorder, n = 119 any psychiatric disorder and n = 70 depression. Patients with depression (EM-D, p=.018; p=.035) or psychiatric condition (EM-P, p=.020; p=.048) suffered more often from dyspareunia and dyschezia. EM-P patients had more often primary dysmenorrhoea with higher pain scores (p=.045). rASRM stage or localisation of lesions did not differ. EM-D and EM-P patients discontinued dienogest treatment more often related to worsening of mood (p= .001, p=.002). CONCLUSION: EM-D or EM-P had a higher prevalence of pain symptoms. This could not be attributed to differences in rASRM stage or location of endometriosis lesions. Strong primary dysmenorrhoea might predispose to develop chronic pain-based psychological symptoms. Therefore, early diagnosis and treatment are relevant. Gynaecologist should be aware of the potential impact of dienogest on mood.


Women with endometriosis and psychiatric disorders especially have more dyschezia and dyspareunia, independent from rASRM stage, depth of infiltration and localisation of endometriosis lesions. Dienogest has an impact on mood especially in already prone patients.Trial registration: trial registration number: NCT04816357. https://clinicaltrials.gov/ct2/show/NCT04816357Date of registration: 22.03.2021, date of enrolment of the first subject: 25.03.2021.


Assuntos
Endometriose , Nandrolona , Humanos , Feminino , Endometriose/complicações , Endometriose/tratamento farmacológico , Endometriose/diagnóstico , Dor Pélvica/etiologia , Dismenorreia/epidemiologia , Estudos de Casos e Controles , Depressão/tratamento farmacológico , Nandrolona/efeitos adversos
17.
Steroids ; 197: 109247, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37149242

RESUMO

AIM: To investigate the effect of acute treatment with the anabolic steroid (AS) nandrolone decanoate in mitochondrial homeostasis and JAK-STAT3 signaling during the progression of cardiac ischemia/reperfusion injury (IR). METHODS: Male Wistar rats (2 months old) were randomly allocated into four experimental groups: Control (CTRL), IR, AS, and AS + AG490. All animals were euthanized 3 days after a single intramuscular injection of nandrolone at 10 mg/kg (AS and AS + AG490 groups) or vehicle (CTRL and IR groups). Baseline mRNA expression of antioxidant enzymes superoxide dismutase (SOD) 1 and 2, glutathione peroxidase, catalase, and myosin heavy chain (MHC) α and ß were compared between CTRL and AS groups. Isolated hearts were submitted to ex vivo ischemia and reperfusion, except for hearts from the CTRL group. Before the IR protocol, the JAK-STAT3 inhibitor AG490 was perfused in hearts from the AS + AG490 group. Heart samples were collected during reperfusion to investigate the effects on mitochondrial function. Results Antioxidant enzyme mRNA expression was unaffected, whereas the AS group exhibited decreased ß- MHC/α-MHC ratio versus the CTRL group. Compared to the IR group, the AS group exhibited better recovery of post-ischemic left ventricular (LV) end-diastolic pressure and LV-developed pressure levels, while infarct size significantly decreased. Furthermore, mitochondrial production, transmembrane potential, and swelling were improved, whereas ROS formation was decreased versus the IR group. These effects were prevented by the perfusion of JAK-STAT3 inhibitor AG490. CONCLUSION: These findings suggest that acute nandrolone treatment can provide cardioprotection by recruiting the JAK-STAT3 signaling pathway and mitochondrial preservation.


Assuntos
Traumatismo por Reperfusão Miocárdica , Nandrolona , Ratos , Animais , Masculino , Antioxidantes , Ratos Wistar , Mitocôndrias/metabolismo , RNA Mensageiro
18.
Reprod Sci ; 30(11): 3135-3143, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37217824

RESUMO

The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative treatments (GnRH agonist, other progestins, and estro-progestins). The design used in this study is systematic review with meta-analysis. The data source includes PubMed and EMBASE searched up to March 2022. A systematic review and meta-analysis were performed in accordance with guidelines from the Cochrane Collaboration. Keywords such as "dienogest," "endometriosis surgery," "endometriosis treatment," and "endometriosis medical therapy" were used to identify relevant studies. The primary outcome was recurrence of endometriosis after surgery. The secondary outcome was pain recurrence. An additional analysis focused on comparing side effects between groups. Nine studies were eligible, including a total of 1668 patients. At primary analysis, dienogest significantly reduced the rate of cyst recurrence compared with placebo (p < 0.0001). In 191 patients, the rate of cyst recurrence comparing dienogest vs GnRHa was evaluated, but no statistically significant difference was reported. In the secondary analysis, a trend toward reduction of pain at 6 months was reported in patients treated with dienogest over placebo, with each study reporting a significantly higher reduction of pain after dienogest treatment. In terms of side effects, dienogest treatment compared with GnRHa significantly increased the rate of spotting (p = 0.0007) and weight gain (p = 0.03), but it was associated with a lower rate of hot flashes (p = 0.0006) and a trend to lower incidence of vaginal dryness. Dienogest is superior to placebo and similar to GnRHa in decreasing rate of recurrence after endometriosis surgery. A significantly higher reduction of pain after dienogest compared with placebo was reported in two separate studies, whereas a trend toward reduction of pain at 6 months was evident at meta-analysis. Dienogest treatment compared with GnRHa was associated with a lower rate of hot flashes and a trend to lower incidence of vaginal dryness.


Assuntos
Cistos , Endometriose , Nandrolona , Feminino , Humanos , Endometriose/tratamento farmacológico , Endometriose/cirurgia , Endometriose/complicações , Progestinas/uso terapêutico , Dor Pélvica/etiologia , Dor Pélvica/tratamento farmacológico , Fogachos , Nandrolona/efeitos adversos , Cistos/induzido quimicamente , Cistos/complicações , Cistos/tratamento farmacológico
19.
Arch Gynecol Obstet ; 308(3): 947-952, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37010614

RESUMO

OBJECTIVES: To compare the effectiveness of dienogest (DIE) and norethisterone acetate (NETA) regimens in the treatment of endometrial hyperplasia (EH) without atypia. METHODS: Participants were premenopausal women with irregular uterine bleeding, and endometrial hyperplasia without atypia on endometrial biopsy. Enrolled patients were randomly allocated into two groups: group I got DIE 2 mg/day (orally Visanne) for 14 days (10th to the 25th day of cycle) while group II received between the 16th and 25th day of the cycle, norethisterone acetate (NETA) 15 mg/d (orally Primolut Nor) was administered for 10 days. Both groups continued the therapy for six months. RESULTS: The DIE group showed a higher resolution (32.7%) and regression (57.7%) than NETA group (31% & 37.9%, respectively) with significant regression (p = 0.039). No progression in DIE group while four (6.9%) women in NETA group were recorded a progression to complex type without a significance. Also, NETA group showed a significant persistence rate (22.5%) than DIE group (3.8%) (p = 0.005). Also number in NETA group managed by hysterectomy with significant difference (p = 0.042). CONCLUSION: If used as first-line treatment, Dienogest produces a better rate of regression and a lower incidence of hysterectomy than Norethisterone Acetate does when used in EH without atypia.


Assuntos
Hiperplasia Endometrial , Nandrolona , Feminino , Humanos , Masculino , Acetato de Noretindrona , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , Nandrolona/uso terapêutico , Endométrio/patologia , Noretindrona/uso terapêutico , Estradiol
20.
BMC Pharmacol Toxicol ; 24(1): 17, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36922878

RESUMO

BACKGROUND: Anabolic steroids (AS) are commonly abused by body builders and athletes aiming to increase their strength and muscle mass but unfortunately, the long-term use of AS may lead to serious side effects. Nandrolone Decanoate is one of the Class II anabolic androgenic steroids which quickly spread globally and used clinically and illicitly. Our research was directed to assess the toxic effects of anabolic steroids on cardiac and skeletal muscles in male albino rats and to evaluate the potential ameliorative effects of fenugreek seeds extract and silymarin. METHODS: Our research was done on 120 male albino rats that were allocated into 6 groups; group I: Served as a control group, group II: Received the anabolic steroid Nandrolone Decanoate, group III: Received silymarin orally, group IV: Received fenugreek seeds extract orally, group (V): Received the anabolic steroid Nandrolone Decanoate and silymarin and group (VI): Received the anabolic steroid Nandrolone Decanoate and fenugreek seeds extract. By the end of the study, rats were sacrificed, and blood samples were collected for biochemical analysis and autopsy samples for histopathological examination. RESULTS: The anabolic steroids toxic effects on rats showed a significant decrease in serum High Density Lipoprotein (HDL) level and increase in cholesterol, triglycerides, and Low-Density Lipoprotein (LDL) levels. There was a significant elevation in cardiac troponin I level. As regards to histopathological examination of the cardiac and skeletal muscles, the study showed marked degenerative changes and necrosis. Both silymarin and fenugreek seeds extract provided a protective effect on the biochemical and histopathological changes. The antioxidant effects of silymarin and fenugreek seeds extract were evaluated on the heart, skeletal muscles and showed that, the tissue levels of Superoxide dismutase (SOD), Catalase and reduced glutathione (GSH) decreased in AS treated rats compared to the control group. On the other hand, the tissue Malondialdehyde (MDA) levels were elevated. CONCLUSIONS: Anabolic steroids have a toxic effect on the cardiac and skeletal muscles of albino rats with improvement by treatment with fenugreek seeds extract and silymarin.


Assuntos
Anabolizantes , Nandrolona , Silimarina , Trigonella , Ratos , Animais , Decanoato de Nandrolona , Nandrolona/toxicidade , Esteróides Androgênicos Anabolizantes , Decanoatos , Silimarina/farmacologia , Anabolizantes/toxicidade , Músculo Esquelético
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