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1.
Contraception ; 108: 56-60, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34848179

RESUMO

OBJECTIVE: To describe use of three types of longer-acting contraception-intrauterine devices, subdermal contraceptives, and depot medroxyprogesterone-among transmasculine and cisgender women patients. STUDY DESIGN: A repeated cross-sectional study using electronic medical records of patients, age 18 to 45, receiving care within Kaiser Permanente Northern California between 2009 and 2019. Variations in demographics, clinical characteristics and contraception method uptake were assessed using t tests for continuous variables and chi-square tests for categorical variables for patients enrolled in 2019. A linear trend test for each group was used to assess the age-adjusted uptake of contraception methods by study year. RESULTS: The transmasculine group was younger, with a mean age of 27.3 years (±7.2) vs 32.5 years (±7.8) years, respectively p < 0.001. The transmasculine group used more tobacco, alcohol, and illicit drugs. The uptake of these contraception methods increased from 2009 to 2019 for both groups (transmasculine: 0.7% to 4.1%; cisgender: 5.6% to 6.7%) with a positive linear trend for both groups (p = 0.003 and p < 0.001, respectively). The change in uptake of any intrauterine device from 2009 to 2019 was greater for the transmasculine group (0.3% to 2.3% vs 3.3% to 3.5%). Etonogestrel implant uptake had a positive linear trend from 2009 to 2019 for both groups (transmasculine: 0% to 0.5%, p = 0.02, and cisgender 0.1% to 1.2%, p < 0.001). CONCLUSION: Annual uptake of these contraception methods increased significantly for both transmasculine and cisgender groups, and this increase was greater for the transmasculine patients. Uptake of these contraception methods was higher in the cisgender population. IMPLICATIONS: These findings suggest an improvement in use of long-term contraception and menstrual suppression medications for the transmasculine population. Further research is needed to understand these differences and identify a possible unmet need for intrauterine and subdermal contraceptives and depot medroxyprogesterone use among this often-marginalized population.


Assuntos
Anticoncepcionais Femininos , Dispositivos Intrauterinos , Adolescente , Adulto , Anticoncepção/métodos , Anticoncepcionais Femininos/uso terapêutico , Estudos Transversais , Implantes de Medicamento , Feminino , Humanos , Medroxiprogesterona , Acetato de Medroxiprogesterona/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem
2.
Am J Reprod Immunol ; 87(1): e13423, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33764560

RESUMO

PROBLEM: Decidualized cells display an active role during embryo implantation sensing blastocyst quality, allowing the implantation of normal developed blastocysts and preventing the invasion of impaired developed ones. Here, we characterized the immune microenvironment generated by decidualized cells in response to soluble factors secreted by blastocysts that shape the receptive milieu. METHOD OF STUDY: We used an in vitro model of decidualization based on the Human Endometrial Stromal Cells line (HESC) differentiated with medroxiprogesterone and dibutyryl-cAMP, then treated with human blastocysts-conditioned media (BCM) classified according to their quality. RESULTS: Decidualized cells treated with BCM from impaired developed blastocysts increased IL-1ß production. Next, we evaluated the ability of decidualized cells to modulate other mediators associated with menstruation as chemokines. Decidualized cells responded to stimulation with BCM from impaired developed blastocysts increasing CXCL12 expression and CXCL8 secretion. The modulation of these markers was associated with the recruitment and activation of neutrophils, while regulatory T cells recruitment was restrained. These changes were not observed in the presence of BCM from normal developed blastocysts. CONCLUSION: Soluble factors released by impaired developed blastocysts induce an exacerbated inflammatory response associated with neutrophils recruitment and activation, providing new clues to understand the molecular basis of the embryo-endometrial dialogue.


Assuntos
Blastocisto/fisiologia , Decídua/metabolismo , Implantação do Embrião/fisiologia , Inflamação/metabolismo , Células Estromais/metabolismo , Blastocisto/efeitos dos fármacos , Linhagem Celular , Decídua/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Feminino , Humanos , Medroxiprogesterona/administração & dosagem , Células Estromais/efeitos dos fármacos
3.
Contraception ; 105: 42-45, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34418379

RESUMO

OBJECTIVES: Females with sickle cell disease now have a life expectancy that extends well into and beyond their reproductive years. Pregnancy and childbirth are accompanied by high morbidity and mortality in this population, rendering contraception a critical part of their health care. STUDY DESIGN: We approached adult female patients of the Hospital of the University of Pennsylvania hematology clinic who were of reproductive age (ages 18-45) and carried a diagnosis of sickle cell disease. We evaluated contraceptive method uptake and method characteristic preferences, as well as other reproductive history, and compared contraceptive uptake rates to that from female respondent data from the National Survey of Family Growth (2017-2019). RESULTS: Of 95 eligible patients, we completed surveys with 48 participants (response rate of 51%). Over half (n = 27, 56%) of participants were not currently using any form of contraception-double the rate of the general United States population (25%). The most common contraceptives currently used were the depot medroxyprogesterone (DMPA) injection (n = 6, 13%) and the progestin intrauterine device (IUD) (n = 6, 13%). DMPA uptake was significantly higher, and permanent contraceptive and oral contraceptive pill uptake significantly lower, among these participants with sickle cell disease compared to the general United States population. Participants' preferred contraceptive characteristics included effectiveness (n = 39, 81%), control over when to use the contraceptive (n = 39, 81%), and lack of side effects (n = 38, 79%). CONCLUSIONS: Contraceptive uptake was significantly lower and method mix different among females with sickle cell disease compared to the general United States population. Further research is needed on contraceptive safety, non-contraceptive benefits, and contraceptive decision-making for females with sickle cell disease. IMPLICATIONS: This study sheds light on the contraceptive choices and preferences of females with sickle cell disease, who are at disproportionate risk for pregnancy complications. In order to maximize the reproductive health of females with sickle cell disease, we must consider how their disease interacts with contraception and better understand how they approach contraceptive decision-making.


Assuntos
Anemia Falciforme , Anticoncepcionais Femininos , Dispositivos Intrauterinos , Adolescente , Adulto , Anticoncepção , Anticoncepcionais Orais , Feminino , Humanos , Medroxiprogesterona , Pessoa de Meia-Idade , Gravidez , Estados Unidos , Adulto Jovem
4.
Gac Sanit ; 35 Suppl 2: S475-S478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34929879

RESUMO

OBJECTIVE: This study aims to determine the relationship between estradiol hormone levels and duration of the usage on sexual dysfunction in Depo Medroxy Progesterone Acetate acceptors. METHOD: Family Planning (KB/Keluarga Berencana) Depo Medroxy Progesterone Acetate as many as 43 respondents who meet the sample criteria. The sampling technique used was accidental sampling. Data analysis was performed by using chi square. RESULTS: The results showed that there was a significant relation between levels of the hormone estradiol and the incidence of sexual dysfunction (p=0.000), as well as the length of time using Depo Medroxy Progesterone Acetate on sexual dysfunction (p=0.000). CONCLUSION: The result of data analysis is that the duration of Depo Medroxy Progesterone Acetate injection usage significantly reduces the level of the hormone estradiol which can cause sexual dysfunction in Depo Medroxy Progesterone Acetate acceptors.


Assuntos
Estradiol , Progesterona , Acetatos , Humanos , Medroxiprogesterona , Acetato de Medroxiprogesterona , Saúde Pública
6.
Front Endocrinol (Lausanne) ; 12: 708704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630325

RESUMO

Objective: To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR). Patients and Methods: This was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates. Results: In total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% vs. 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% vs. 29.6%, P=0.14). Conclusion: For women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.


Assuntos
Didrogesterona/farmacologia , Fertilização In Vitro/métodos , Infertilidade Feminina/terapia , Medroxiprogesterona/farmacologia , Oócitos/efeitos dos fármacos , Indução da Ovulação/métodos , Progestinas/farmacologia , Adulto , Anticoncepcionais Orais Hormonais/farmacologia , Feminino , Seguimentos , Humanos , Recuperação de Oócitos , Oócitos/patologia , Gravidez , Resultado da Gravidez , Prognóstico , Estudos Retrospectivos
7.
Sovrem Tekhnologii Med ; 13(1): 93-106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513071

RESUMO

This review summarizes the current opinions on the mechanisms of action of nuclear, mitochondrial, and membrane progesterone receptors. The main aspects of the pharmacological action of progestins have been studied. Data on the clinical use of gestagens by nosological groups are presented. Particular attention is paid to progesterone, megestrol acetate, medroxyprogesterone acetate due to broadening of their spectrum of action. The possibilities of using gestagens as neuroprotectors, immunomodulators, and chemosensitizers are considered.


Assuntos
Megestrol , Progestinas , Medroxiprogesterona , Acetato de Medroxiprogesterona/farmacologia , Progesterona
8.
Trop Anim Health Prod ; 53(3): 345, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34091738

RESUMO

We evaluated if alternative treatments achieve at least similar results as traditional long treatments with intravaginal sponges (IVS) in three experiments considering (1) the use of 6-day treatments associated or not with the administration of PGF2alpha at IVS insertion; (2) a reduction of 50% MAP content in short-term or traditional treatments, with or without change of the IVS 6 days after its insertion; and (3) the substitution of IVS for long-time acting injected progesterone associated with the administration of a PGF2alpha. More ewes came into estrus with long than short IVS treatments, independently of the MAP IVS content. Fewer ewes came into estrus if the IVS containing 30 mg was replaced 6 days after its insertion. The length of the treatment did not affect the conception rate, but the pregnancy rate was greater in 12 than 6 days treatments. The administration of long-acting progesterone did not prevent the lower conception rate associated with the use of PGF2alpha and was less effective to synchronize estrus, but the conception rate did not differ from that of 12d IVS treatments. Overall, MAP content could be decreased without affecting the estrous rate; thereafter, the MAP IVS content should be decreased in the commercial devices. Although pregnancy rate was lower using long-acting injected progesterone than with IVS, as the conception rate did not differ, it is interesting to study deeper the use of this treatment, especially if preparations of progesterone with a longer half-life are developed. However considering all the results, the traditional long IVS treatment still provided the best result.


Assuntos
Medroxiprogesterona , Progesterona , Administração Intravaginal , Animais , Dinoprosta , Estro , Sincronização do Estro , Feminino , Inseminação Artificial/veterinária , Gravidez , Ovinos
9.
Arq. bras. med. vet. zootec. (Online) ; 73(3): 752-756, May-June 2021. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278366

RESUMO

O presente trabalho objetivou avaliar os efeitos da administração em dose única de progestágenos em fêmeas caninas hígidas, as quais nunca haviam recebido tais fármacos. Foram selecionadas 20 cadelas, que foram examinadas clinicamente e por meio de exames complementares. Nessas cadelas, foi aplicado medroxiprogesterona por via subcutânea. Noventa dias após, as fêmeas foram esterilizadas cirurgicamente, sendo os tecidos reprodutivos encaminhados para histopatologia. Foi possível verificar que, aos 30 dias, 12 animais (60%) apresentaram hiperplasia mamária. Aos 90 dias, 18 animais (90%) apresentavam sinais de hiperplasia endometrial cística, tendo cinco (27,77%) destes animais apresentado conteúdo purulento no lúmen uterino. No exame microscópico, apenas uma fêmea não demonstrou alterações patológicas, sendo a única que recebeu o contraceptivo na fase correta (anestro). As demais fêmeas apresentaram alterações que variaram entre alterações circulatórias a hiperplasia endometrial cística grave. Assim, foi possível concluir que uma única aplicação de anticoncepcional em fêmeas hígidas pode causar complicações leves a graves.(AU)


Assuntos
Animais , Feminino , Cães , Progestinas/uso terapêutico , Anticoncepcionais/administração & dosagem , Anticoncepcionais/efeitos adversos , Hiperplasia Endometrial/veterinária , Medroxiprogesterona/administração & dosagem
10.
Biochem Biophys Res Commun ; 548: 148-154, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33640608

RESUMO

Endocrine therapy is a promising treatment for endometrial cancer (EC) that preserves fertility, however, progesterone-resistance is currently the major challenges. The Cancer Genome Atlas (TCGA) database analysis showed that CNR1 was closely have a negative correlation with overall survival (OS) and relapse-free survival (RFS) in endometrial cancer. To explore the role of CNR1 in progesterone resistance and possible molecular regulation mechanism, we established stable progesterone-resistant cell lines (IshikawaPR) via progesterone tolerance of ordinary cancer cells (Ishikawa). The difference of CNR1 level in two cell lines was assessed by MTT, RT-PCR, Western blot, immunofluorescence. Then, lentiviruses constructed CNR1-knockdown with GV248 as the tool vector were used to transfect IshikwaPR cells, and the changes of biological behavior and progesterone sensitivity was verified respectively through plate cloning experiment, EdU assay, flow cytometry cycle analysis, transwell, Scratch test, etc. We founded after CNR1 was knocked down, the proliferative activity and ability to migrate of IshikawaPR cells decreased, progesterone-response sensitivity could be improved. Moreover, knockdown of CNR1 can also down-regulate ERK and NFκ B expression and activation. Furthermore, subcutaneous xenograft in nude mice was tested similarly in vivo. The above datas suggest that targeting CNR1 may reverse the progesterone resistance in endometrial cancer and may coordinate the role of ERK pathway activation.


Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Endométrio/anormalidades , Sistema de Sinalização das MAP Quinases , Receptor CB1 de Canabinoide/metabolismo , Doenças Uterinas/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias do Endométrio/genética , Endométrio/metabolismo , Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Medroxiprogesterona/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptor CB1 de Canabinoide/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Doenças Uterinas/genética , Doenças Uterinas/patologia
11.
J Med Case Rep ; 15(1): 92, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618767

RESUMO

BACKGROUND: Gynecologic anomalies, including uterine agenesis and ovarian dysgenesis, are some of the several differential diagnoses in adolescent females with primary amenorrhea and delayed puberty. Primary ovarian insufficiency is reported in the clinical practice of reproductive endocrinology can be determined by conducting sex hormone tests to evaluate the hypothalamic-pituitary-ovarian axis. However, confirmation of Mullerian agenesis by image modalities can be extremely challenging. Once the diagnosis is established, breakthrough bleeding usually occurs 2 to 3 years after hormonal replacement therapy. CASE PRESENTATION: We report a case of a seventeen year old Taiwanese female, 46 XX karyotype, with ovarian dysgenesis and an initial tentative diagnosis of uterine agenesis who experienced a breakthrough bleeding after a month of hormonal replacement therapy. CONCLUSIONS: The breakthrough bleeding after a month of estrogen therapy in primary ovarian insufficiency is uncommon, and the diagnosis of the absent uterus can have an extensive psychological impact on patients and their families.


Assuntos
Terapia de Reposição Hormonal , Menarca/efeitos dos fármacos , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/tratamento farmacológico , Adolescente , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Humanos , Medroxiprogesterona/uso terapêutico , Taiwan/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Anormalidades Urogenitais/diagnóstico por imagem , Útero/anormalidades , Útero/diagnóstico por imagem
12.
Eur J Ophthalmol ; 31(2): NP33-NP38, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32141311

RESUMO

INTRODUCTION: Mooren's ulcer is a painful, inflammatory chronic keratitis that affects corneal periphery, progressing centripetally, ultimately ending in perforation. The first line of treatment includes systemic immunomodulators, with surgery being the last option. We present a case of bilateral Boston keratoprosthesis implantation for severe Mooren's ulcer that responded differently in each eye. CLINICAL CASE: A 32-year-old male with corneal opacification, anterior staphylomas, vision of hand movement, was started on systemic immunosuppression with cyclosporine. After two failed penetrating keratoplasties in each eye, high intraocular pressure despite diode cyclophotocoagulation, and cystic macular edema, we performed Boston keratoprosthesis type 1 in both eyes. The right eye responded initially well, with a best-corrected visual acuity of 20/80 and normal intraocular pressure. The left eye presented high intraocular pressure, which required cyclophotocoagulation, ultimately resulting in hypotony. Boston keratoprosthesis was performed but had peripheral corneal necrosis that progressed despite amniotic membrane transplantation and aggressive intensive treatment with medroxyprogesterone, autologous platelet-rich-in-growth-factors eye drops, and oral doxycycline. Thus, replacement of the semi-exposed Boston keratoprosthesis with tectonic penetrating keratoplasty was necessary. However, both eyes developed phthisis bulbi with final visual acuity of perception of light with poor localization. CONCLUSION: Mainstay treatment of Mooren's ulcer is systemic immunomodulation. Surgical treatment must be considered only when risk of perforation, preferably with inflammation under control. Penetrating keratoplasty frequently fails, and Boston keratoprosthesis may be a viable option. However, postoperative complications, especially uncontrolled high intraocular pressure, corneal necrosis, and recurrence of Mooren's ulcer may jeopardize the outcomes and need to be addressed promptly with intensive topical and systemic treatment.


Assuntos
Órgãos Artificiais , Córnea , Úlcera da Córnea/cirurgia , Próteses e Implantes , Adulto , Antibacterianos/uso terapêutico , Terapia Combinada , Anticoncepcionais Orais Hormonais/uso terapêutico , Doxiciclina/uso terapêutico , Seguimentos , Humanos , Ceratoplastia Penetrante , Masculino , Medroxiprogesterona/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Plasma Rico em Plaquetas/fisiologia , Recidiva , Úlcera , Acuidade Visual
13.
Eur J Clin Pharmacol ; 77(1): 133-140, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32803291

RESUMO

PURPOSE: To examine whether there is a positive association between sexual dysfunction (SD) and different types of progestin-based contraceptives. METHODS: Nested case-control study in women of child-bearing age (15-45 years) from the IQVIA® Ambulatory electronic medical record database from 2008 to 2018. Cases defined by diagnosis of sexual dysfunction identified by international classification for disease clinical modification code 9th and 10th. Each case was matched to four controls and rates of prescriptions of the following were compared: levonorgestrel intra-uterine device (IUD), progestin, and ethinyl estradiol (EE) combined oral contraceptive (COC) formulations including levonorgestrel, norgestimate, drospirenone, desogestrel, norethindrone, and norgestrel; etonogestrel vaginal ring; and medroxyprogesterone injection. RESULTS: Overall, 6689 cases of patients with SD were matched to 26,756 matched controls. Compared with matched controls, more subjects with SD used levonorgestrel IUD (OR 1.24, 95% CI 1.08-1.44), EE-levonorgestrel COC (OR 1.18, 95% CI 1.00-1.41), EE-drospirenone (OR 1.28, 95% CI 1.00-1.67), and medroxyprogesterone (OR 1.38, 95% CI 1.12-1.70). The use of norgestrel exhibited a protective effect (OR 0.83, 95% CI 0.73-0.95). When using the EE-levonorgestrel COC as a comparator, norgestrel users exhibited a protective effect (OR 0.70, 95% CI 0.57-0.87) while no other contraceptives showed a statistically significant difference in association with SD. CONCLUSION: Our study found an increase in the use of levonorgestrel (COC and IUD), drospirenone, and medroxyprogesterone in subjects with SD. The risk of contraceptives did not differ when compared with oral levonorgestrel. The small association size and lack of difference between drug formulations suggest a minimal impact of progestin-based contraceptives on sexual dysfunction.


Assuntos
Progestinas/efeitos adversos , Disfunções Sexuais Fisiológicas/epidemiologia , Adolescente , Adulto , Androstenos/efeitos adversos , Estudos de Casos e Controles , Combinação de Medicamentos , Etinilestradiol/efeitos adversos , Feminino , Humanos , Dispositivos Intrauterinos/efeitos adversos , Levanogestrel/efeitos adversos , Medroxiprogesterona/efeitos adversos , Pessoa de Meia-Idade , Adulto Jovem
14.
BMJ Support Palliat Care ; 11(1): 75-85, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33246937

RESUMO

AIMS: Randomised controlled trials (RCTs) demonstrated benefits of pharmacological interventions for cachexia in improving weight and appetite. However, comparative efficacy and safety are not available. We conducted a systematic review and network meta-analysis (NMA) to evaluate the relative efficacy and safety of pharmacological interventions for cachexia. METHODS: PubMed, EmBase, Cochrane, and ClinicalTrials.gov were searched for RCTs until October 2019. Key outcomes were total body weight (TBW) improvement, appetite (APP) score and serious adverse events. Two reviewers independently extracted data and assessed risk of bias. NMA was performed to estimate weight gain and APP score increase at 8 weeks, presented as mean difference (MD) or standardised MD with 95% CI. RESULTS: 80 RCTs (10 579 patients) with 12 treatments were included. Majority is patients with cancer (7220). Compared with placebo, corticosteroids, high-dose megestrol acetate combination (Megace_H_Com) (≥400 mg/day), medroxyprogesterone, high-dose megestrol acetate (Megace_H) (≥400 mg/day), ghrelin mimetic and androgen analogues (Androgen) were significantly associated with MD of TBW of 6.45 (95% CI 2.45 to 10.45), 4.29 (95% CI 2.23 to 6.35), 3.18 (95% CI 0.94 to 5.41), 2.66 (95% CI 1.47 to 3.85), 1.73 (95% CI 0.27 to 3.20) and 1.50 (95% CI 0.56 to 2.44) kg. For appetite improvement, Megace_H_Com, Megace_H and Androgen significantly improved standardised APP score, compared with placebo. There is no significant difference in serious adverse events from all interventions compared with placebo. CONCLUSIONS: Our findings suggest that several pharmacological interventions have potential to offer benefits in treatment of cachexia especially Megace_H and short-term use corticosteroids. Nonetheless, high-quality comparative studies to compare safety and efficacy are warranted for better management of cachexia.


Assuntos
Corticosteroides/administração & dosagem , Estimulantes do Apetite/administração & dosagem , Caquexia/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Acetato de Megestrol/administração & dosagem , Androgênios/administração & dosagem , Apetite/efeitos dos fármacos , Caquexia/etiologia , Pesquisa Comparativa da Efetividade , Quimioterapia Combinada , Grelina/administração & dosagem , Humanos , Medroxiprogesterona/administração & dosagem , Diferença Mínima Clinicamente Importante , Neoplasias/complicações , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Assistência Terminal/métodos , Ganho de Peso/efeitos dos fármacos
16.
Anim Reprod Sci ; 223: 106644, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33197710

RESUMO

This study was conducted in ewes to assess effects of human chorionic gonadotropin (hCG) administration after imposing an estrous induction treatment regimen. Ewes (n = 115) were treated with a 60 mg medroxyprogesterone-intravaginal-sponge for 6 d plus 200 IU of equine chorionic gonadotropin (eCG) im and 37.5 µg d-cloprostenol im 36 h before sponge removal (Day 0). After natural mating, ewes having at least one corpus luteum (CL; n = 108) were administered either 1 mL of saline (G-Control; n = 53) or 300 IU of hCG (G-hCG; n = 55) on Day 7.5 after sponge removal (Day 0). Ovarian ultrasonography and blood collection were performed on Days 7.5, 13.5, 17.5, 21.5, and 30.5. Accessory CL (aCL) were observed in 81.5 % (G-hCG) and 0.0 % (G-Control) of ewes (P = 0.0001). Diameter, area, and volume of luteal tissue were greater (P < 0.05) in G-hCG from Day 13.5 to 30.5. Progesterone (P4) concentrations were greater (P < 0.05) on Days 13.5, 17.5, 21.5 and 30.5 for ewes of the G-hCG group. Pregnancy percentage was similar (P = 0.25) between groups [47.1 % (G-control) compared with 60.0 % (G-hCG)], although total number of lambs produced by estrous synchronized ewes was greater (P = 0.005) in ewes of the G-hCG group (90.9 % compared with 66.0 %). In conclusion, hCG administration 7.5 days after sponge removal from Morada Nova ewes during the non-breeding season is an effective treatment to induce aCL formation, improve luteal tissue biometry and P4 concentrations, and to enhance the total number of lambs born.


Assuntos
Gonadotropina Coriônica/farmacologia , Corpo Lúteo/efeitos dos fármacos , Sincronização do Estro/efeitos dos fármacos , Ovinos , Animais , Gonadotropina Coriônica/administração & dosagem , Cloprostenol/farmacologia , Anticoncepcionais Orais Hormonais/farmacologia , Esquema de Medicação , Feminino , Humanos , Luteolíticos/farmacologia , Medroxiprogesterona/administração & dosagem , Medroxiprogesterona/farmacologia , Gravidez , Progesterona/sangue , Substâncias para o Controle da Reprodução/administração & dosagem , Substâncias para o Controle da Reprodução/farmacologia
17.
Menopause ; 27(12): 1411-1419, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33109993

RESUMO

OBJECTIVE: Our laboratory previously published that long-term administration of estradiol (E2) was detrimental to the kidneys of midlife ovariectomized Long Evans rats, contrasting clinical studies in showing that menopausal hormone therapy is associated with decreased albuminuria. However, it is unknown whether this renal benefit was due to estrogen and/or the combination with progestogen. Therefore, the objective of the current study was to determine the impact of medroxyprogesterone (MPA) on E2-mediated renal damage using a rodent model. METHODS: Female Long Evans retired breeders underwent ovariectomy at 11 months of age and were treated for 40 days with subcutaneous E2, E2+MPA or vehicle at doses mimicking that of menopausal hormone therapy (N = 5-7 per group). Systolic blood pressure was measured along with indices of renal damage and function to investigate the impact of MPA on E2-mediated renal outcomes. Renal estrogen receptor alpha and G protein-coupled estrogen receptor transcript copy numbers were measured in all treatment groups through droplet digital PCR. RESULTS: Middle-aged female Long Evans rats displayed spontaneous hypertension with similar systolic blood pressures and heart weights between groups. Even though blood pressure was comparable, E2 reduced glomerular filtration rate and increased proteinuria indicating pressure-independent renal damage. Coadministration with MPA prevented E2-induced glomerular filtration rate impairment and proteinuria by promoting renal hypertrophy and preventing renal interstitial fibrosis. Both E2 and E2+MPA reduced renal estrogen receptor alpha (ERα) and increased renal G protein-coupled estrogen receptor mRNA, but neither ERα nor ERß protein was different between groups. CONCLUSION: MPA was protective against E2-induced renal damage and dysfunction in middle-aged female Long Evans rats. Assessing the impact of hormone therapy on renal outcomes may be an important clinical factor when considering treatment options for postmenopausal women.


Assuntos
Estradiol , Medroxiprogesterona , Animais , Estrogênios , Feminino , Humanos , Rim , Pessoa de Meia-Idade , Ovariectomia , Ratos , Ratos Long-Evans
18.
Ups J Med Sci ; 125(4): 325-329, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33043759

RESUMO

More effective treatments are needed for low-grade serous ovarian carcinoma (LGSOC). Our patient, who suffers from metastatic LGSOC, had received all established treatments. Sequencing analysis revealed an activating BRAF mutation. Therefore, combined treatment with BRAF and MEK inhibitors, which is the gold standard in malignant melanoma, was initiated. After eight months of therapy, the response was assessed as complete and the treatment is still, 3.5 years after initiation, of benefit. To our knowledge, no complete response on combined BRAF and MEK inhibitor treatment of low-grade serous ovarian cancer has previously been reported.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , MAP Quinase Quinase 1/antagonistas & inibidores , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Antineoplásicos/farmacologia , Benzimidazóis/administração & dosagem , Bevacizumab/administração & dosagem , Antígeno Ca-125/sangue , Carbamatos/administração & dosagem , Carboplatina/administração & dosagem , Progressão da Doença , Everolimo/administração & dosagem , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imidazóis/administração & dosagem , Medroxiprogesterona/administração & dosagem , Metástase Neoplásica , Recidiva Local de Neoplasia , Oximas/administração & dosagem , Paclitaxel/administração & dosagem , Intervalo Livre de Progressão , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Recidiva , Sulfonamidas/administração & dosagem , Tamoxifeno/administração & dosagem , Resultado do Tratamento , Adulto Jovem
19.
Steroids ; 164: 108735, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32976918

RESUMO

The fungal transformations of medroxyrogesterone (1) were investigated for the first time using Cunninghamella elegans, Trichothecium roseum, and Mucor plumbeus. The metabolites obtained are as following: 6ß, 20-dihydroxymedroxyprogesterone (2), 12ß-hydroxymedroxyprogesterone (3), 6ß, 11ß-dihydroxymedroxyprogesterone (4), 16ß-hydroxymedroxyprogesterone (5), 11α, 17-dihydroxy-6α-methylpregn-4-ene-3, 20-dione (6), 11-oxo-medroxyprogesterone (7), 6α-methyl-17α-hydroxypregn-1,4-diene-3,20-dione (8), and 6ß-hydroxymedroxyprogesterone (9), 15ß-hydroxymedroxyprogesterone (10), 6α-methyl-17α, 11ß-dihydroxy-5α-pregnan-3, 20-dione (11), 11ß-hydroxymedroxyprogesterone (12), and 11α, 20-dihydroxymedroxyprogesterone (13). Among all the microbial transformed products, the newly isolated biotransformed product 13 showed the most potent activity against proliferation of SH-SY5Y cells. Compounds 12, 5, 6, 9, 11, and 3 (in descending order of activity) also showed some extent of activity against SH-SY5Y tumour cell line. The never been reported biotransformed product, 2, showed the most potent inhibitory activity against acetylcholinesterase. Molecular modelling studies were carried out to understand the observed experimental activities, and also to obtain more information on the binding mode and the interactions between the biotransformed products, and enzyme.


Assuntos
Proliferação de Células/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Medroxiprogesterona/farmacologia , Animais , Biotransformação , Caenorhabditis elegans/metabolismo , Inibidores da Colinesterase/química , Simulação por Computador , Cunninghamella/metabolismo , Hypocreales/metabolismo , Técnicas In Vitro , Medroxiprogesterona/química , Medroxiprogesterona/farmacocinética , Simulação de Acoplamento Molecular , Análise Espectral/métodos
20.
Sci Rep ; 10(1): 8298, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427839

RESUMO

Turner Syndrome (TS) is associated with an increased risk of cardiovascular and metabolic complications. Furthermore, TS women need hormone replacement therapy (HRT), of which progestins can influence body weight. We aimed to analyze the metabolic and weight profile in a cohort of 111 TS women. They started receiving estrogen at 15.8 (±3.6) years old, with no change in hypertension, dysglycemia, and dyslipidemia incidence but with a tendency to increase overweight (p = 0.054). As the first used type of progestin, most had received cycles of 10 days per month of medroxyprogesterone (MPA) or levonorgestrel (LNG), then shifted to micronized progesterone (MP), which has currently become the most used one. By multiple linear regression analysis, we found that the prolonged use of MPA, LNG, or MP showed no metabolic change except for weight gain. The percentage of annual BMI increment was positive for all progestins used in TS women (MPA 2.2 ± 2.2; LNG 0.2 ± 1.2; and MP 2.2 ± 2.6 kg/m2), but LNG seemed to best prevent on weight gain over time (p < 0.05). In conclusion, metabolic comorbidities are prevalent in TS even before the HRT regimen, and LNG performed better on less weight gain than MPA and MP in our cohort of the TS population.


Assuntos
Contraceptivos Hormonais/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Levanogestrel/administração & dosagem , Síndrome de Turner/tratamento farmacológico , Ganho de Peso/efeitos dos fármacos , Adolescente , Adulto , Índice de Massa Corporal , Contraceptivos Hormonais/farmacologia , Estudos Transversais , Feminino , Humanos , Levanogestrel/farmacologia , Medroxiprogesterona/administração & dosagem , Medroxiprogesterona/farmacologia , Progestinas/administração & dosagem , Progestinas/farmacologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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