Реферат
This study aims to observe the effect and explore the mechanism of Qirong Tablets in the treatment of premature ovarian insufficiency(POI) in mice via the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor 1(HIF-1) signaling pathway. Sixty SPF female BALB/c mice were randomly divided into normal group, model group, positive control group, Qirong Tablets low-, medium-and high-dose group. The normal group was intraperitoneally injected with the same amount of normal saline, and the other groups were intraperitoneally injected with cyclophosphamide 120 mg·kg~(-1)·d~(-1) once to establish a POI animal model. After the model was successfully established, the low-, medium-and high-dose groups of Qirong Tablets were administered orally with 0.6, 1.2, 2.4 mg·kg~(-1)·d~(-1) respectively. The positive control group was given 0.22 mg·kg~(-1)·d~(-1) Clementine Tablets by intragastric administration, and the normal group and model group were given intragastric administration with the same amount of normal saline, and the treatment was 28 d as a course of treatment. After drug intervention, enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-mullerian hormone(AMH) in peripheral blood, and hematoxylin-eosin(HE) staining to observe the ovarian tissue. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay was used to detect the apoptosis of granulosa cells, and Western blot to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, PI3K, Akt, and HIF-1. Compared with the normal group, the modeling of POI caused loose or destroyed ovarian tissue with vacuolar structures, edema and fibrosis in the ovarian interstitium, disordered or loose arrangement of granulosa cells, and reduced normal follicles. Compared with the model group, drug interventions restored the ovarian tissue and follicles at all the development stages and reduced atretic follicles. Compared with the normal group, the modeling of POI lowered the serum level of E_2 and AMH(P<0.01), and elevated the level of FSH and LH(P<0.01). Compared with the model group, high-dose Qirong Tablets elevated the levels of E_2 and AMH(P<0.05), and lowered the levels of FSH and LH(P<0.05). Compared with the normal group, the modeling of POI up-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 and down-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.01). Compared with the model group, low-, medium-, and high-dose Qirong Tablets down-regulated the protein levels of PI3K, Akt, HIF-1, Bax, and caspase-3 proteins and up-regulated the protein level of Bcl-2 in the ovarian tissue(P<0.05). In conclusion, Qirong Tablets can up-regulate the expression Bcl-2, down-regulate the expression of Bax and caspase-3 in POI mice. Qirong Tablets may inhibit the apoptosis of follicular granulosa cells in mice, thereby delaying ovarian aging, improving reproductive axis function, and strengthening ovarian reserve capacity, which may be associated with the inhibition of PI3K/Akt/HIF-1 pathway.
Тема - темы
Humans , Mice , Female , Animals , Proto-Oncogene Proteins c-akt/metabolism , bcl-2-Associated X Protein , Phosphatidylinositol 3-Kinases/metabolism , Caspase 3/metabolism , Saline Solution/therapeutic use , Signal Transduction , Granulosa Cells , Primary Ovarian Insufficiency/drug therapy , Follicle Stimulating Hormone/therapeutic use , Proto-Oncogene Proteins c-bcl-2/metabolism , ApoptosisРеферат
Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.
Тема - темы
Child , Humans , Female , Primary Ovarian Insufficiency/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Vascular Endothelial Growth Factor A , Medicine, Chinese Traditional , NF-kappa B , KidneyРеферат
El objetivo de este manuscrito es realizar una revisión y actualización de la literatura de la insuficiencia ovárica primaria (IOP) en población adolescente, a partir del diagnóstico, manejo y seguimiento de un caso clínico. La insuficiencia ovárica primaria se define como la menopausia en una mujer antes de los 40 años, acompañada de amenorrea, hipogonadismo hipergonadotrópico e infertilidad. Su prevalencia varía entre 1 a 2%, y en mujeres menores de 20 años su prevalencia es un caso de cada 10,000. Aunque se sabe que muchas afecciones pueden llevar a una IOP, la más común es la causa idiopática. La presentación clínica es diversa, y varios trastornos diferentes pueden también, llevar a esta condición. CASO CLÍNICO: Se presenta el caso de una adolescente de 17 años, previamente sana, con historia de amenorrea secundaria, no embarazada, con examen físico general y ginecológico normal. Se solicita estudio analítico complementario resultando con niveles de hormona folículo estimulante (FHS), estradiol (E2) y hormona antimülleriana (AMH) compatibles con una insuficiencia ovárica como la observada en la posmenopausia. Se inicia terapia hormonal (TH) clásica con estradiol y progesterona, siendo posteriormente reemplazada por anticoncepción hormonal combinada (AHC) oral, coincidente con el inicio de vida sexual, con respuesta favorable y sangrados regulares. La IOP tiene graves consecuencias para la salud incluyendo trastornos psicológicos como angustia, síntomas depresivos o depresión, infertilidad, osteoporosis, trastornos autoinmunes, cardiopatía isquémica, y un mayor riesgo de mortalidad. La enfermedad de Hashimoto es el trastorno autoinmune más frecuente asociado a la IOP. Su tratamiento y diagnóstico deben establecerse de forma precoz para evitar consecuencias a largo plazo. La terapia con estrógenos es la base del tratamiento para eliminar los síntomas de la deficiencia de estrógenos, además de evitar las consecuencias futuras del hipogonadismo no tratado. También el manejo debe incluir los siguientes dominios: fertilidad y anticoncepción, salud ósea, problemas cardiovasculares, función psicosexual, psicológica y neurológica, informando a los familiares y a la paciente sobre la dimensión real de la IOP y la necesidad de tratamiento multidisciplinario en muchos casos. CONCLUSIÓN: El caso presentado, pese a ser infrecuente, permite abordar de manera sistematizada el diagnostico de IOP y evaluar alternativas de manejo plausibles para evitar graves consecuencias en la salud, así como conocer respuesta clínica y de satisfacción de la adolescente.
The objective of this manuscript is to review and update the literature on primary ovarian insufficiency (POI) in an adolescent population, based on the diagnosis, management and follow-up of a clinical case. Primary ovarian insufficiency is defined as menopause in a woman before the age of 40, accompanied by amenorrhea, hypergonadotropic hypogonadism, and infertility. Its prevalence varies between 1 to 2%, and in women under 20 years of age its prevalence is one case in every 10,000. Although it is known that many conditions can lead to POI, the most common is the idiopathic cause. The clinical presentation is diverse, and several different disorders can also lead to this condition. CLINICAL CASE: The case of a 17-year-old adolescent, previously healthy, with a history of secondary amenorrhea, not pregnant, with a normal general physical and gynecological examination is presented. A complementary analytical study is requested, resulting in levels of follicle stimulating hormone (FHS), estradiol (E2) and anti-müllerian hormone (AMH) compatible with ovarian insufficiency such as that observed in postmenopause. Classic hormonal therapy (HT) with estradiol and progesterone was started, later being replaced by combined hormonal contraception (CHC), coinciding with the beginning of sexual life, with a favorable response and regular bleeding. POI has serious health consequences including psychological disorders such as distress, depressive symptoms or depression, infertility, osteoporosis, autoimmune disorders, ischemic heart disease, and an increased risk of mortality. Hashimoto's disease is the most common autoimmune disorder associated with POI. Its treatment and diagnosis must be established early to avoid long-term consequences. Estrogen therapy is the mainstay of treatment to eliminate the symptoms of estrogen deficiency, in addition to avoiding the future consequences of untreated hypogonadism. Management should also include the following domains: fertility and contraception, bone health, cardiovascular problems, psychosexual, psychological and neurological function, informing family members and the patient about the real dimension of POI and the need for multidisciplinary treatment in many cases. CONCLUSION: The case, although infrequent, allows a systematic approach to the diagnosis of POI and evaluate plausible management alternatives to avoid serious health consequences, as well as to know the clinical response and satisfaction of the adolescent.
Тема - темы
Humans , Female , Pregnancy , Adolescent , Primary Ovarian Insufficiency/diagnosis , Primary Ovarian Insufficiency/drug therapy , Menopause, Premature , Hormone Replacement Therapy , Estradiol/analysis , Anti-Mullerian Hormone/analysis , Amenorrhea/etiology , Follicle Stimulating Hormone/analysis , Infertility, FemaleРеферат
Chitooligosaccharide-zinc (COS·Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg·kg
Тема - темы
Animals , Female , Humans , Mice , Chitosan , NF-E2-Related Factor 2/genetics , Nuclear Proteins , Oligosaccharides , Primary Ovarian Insufficiency/drug therapy , Signal Transduction , ZincТема - темы
Humans , Female , Primary Ovarian Insufficiency/diagnosis , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/drug therapy , Testosterone/therapeutic use , Brazil , Hormone Replacement Therapy , Estradiol/therapeutic use , Estrogens/therapeutic use , Evidence-Based Practice , Ambulatory Care/methodsРеферат
Premature ovarian failure has an overall prevalence of 0.3 percent to 0.9 percent in general population. If fertility is a concern, treatment usually consists of estrogen therapy as hormone replacement and oocyte donation. Spontaneous pregnancy in affected women is uncommon. We report a case of a 34-year old woman, who had premature ovarian failure and primary hypothyroidism, and conceived spontaneously eleven years after the development of premature ovarian failure and correction of hypothyroidism.
A falência ovariana prematura tem uma prevalência global variando de 0,3 por cento a 0,9 por cento na população em geral. Nos casos em que existe preocupação com a fertilidade, o tratamento geralmente consiste de terapia de reposição hormonal com estrógeno e doação de oócitos. A gravidez espontânea em mulheres afetadas não é comum. Relatamos um caso de uma mulher de 34 anos de idade que apresentou falência ovariana prematura e hipotireoidismo primário e concebeu espontaneamente onze anos após o desenvolvimento da falência ovariana prematura e da correção do hipotireoidismo.
Тема - темы
Female , Humans , Pregnancy , Hypothyroidism/drug therapy , Pregnancy Complications , Pregnancy Outcome , Primary Ovarian Insufficiency/drug therapy , Estrogen Replacement Therapy , Hypothyroidism/diagnosis , Primary Ovarian Insufficiency/diagnosis , Thyroxine/therapeutic useРеферат
CONTEXT AND OBJECTIVE: Studies on postmenopausal women have reported increased risk of breast cancer relating to the type and duration of hormone therapy (HT) used. Women with premature ovarian failure (POF) represent a challenge, since they require prolonged HT. Little is known about the impact of prolonged HT use on these women's breasts. This study aimed to evaluate the effects of one type of HT on the breast density of women with POF, compared with postmenopausal women. DESIGN AND SETTING: Cross-sectional study at the Department of Obstetrics and Gynecology, Universidade Estadual de Campinas (Unicamp). METHODS: 31 women with POF and 31 postmenopausal women, all using HT consisting of conjugated equine estrogen combined with medroxyprogesterone acetate, and matched according to HT duration, were studied. Mammography was performed on all subjects and was analyzed by means of digitization or Wolfe's classification, stratified into two categories: non-dense (N1 and P1 patterns) and dense (P2 and Dy). RESULTS: No significant difference in breast density was found between the two groups through digitization or Wolfe's classification. From digitization, the mean breast density was 24.1 percent ± 14.6 and 18.1 percent ± 17.2 in the POF and postmenopausal groups, respectively (P = 0.15). Wolfe's classification identified dense breasts in 51.6 percent and 29.0 percent, respectively (P = 0.171). CONCLUSION: There was no difference in breast density between the women with POF and postmenopausal women, who had used HT for the same length of time. These results may help towards compliance with HT use among women with POF.
CONTEXTO E OBJETIVO: Estudos com mulheres na pós-menopausa relatam aumento no risco de câncer de mama relacionado ao tipo e duração da terapia hormonal (TH) utilizada. Mulheres com falência ovariana prematura (FOP) representam desafio por necessitarem de TH prolongada. Pouco se conhece sobre ação da TH nas mamas dessas mulheres. Este estudo objetivou avaliar os efeitos de um tipo de TH sobre a densidade mamária de mulheres com FOP comparativamente à de mulheres pós-menopausa. TIPO DE ESTUDO E LOCAL: Estudo de corte transversal no Departamento de Tocoginecologia, Universidade Estadual de Campinas (Unicamp). MÉTODOS: Estudaram-se 31 mulheres com FOP e 31 mulheres na pós-menopausa, todas usando TH com estrogênio conjugado equino mais acetato de medroxiprogesterona, pareadas pelo tempo de utilização da TH. Todas realizaram mamografia, analisada por digitalização e por classificação de Wolfe, estratificada em duas categorias: não densa (padrão N1 e P1) e densa (P2 e Dy). RESULTADOS: Não houve diferença significativa entre a densidade mamária dos grupos analisadas por digitalização ou classificação de Wolfe. Pela digitalização, calculou-se densidade mamária média em 24.1 por cento ± 14.6 e 18.1 por cento ± 17.2 nas com FOP e pós-menopausa, respectivamente (P = 0,15); pela classificação de Wolfe identificou-se mamas densas em 51,6 por cento e 29,0 por cento, respectivamente (P = 0,171). CONCLUSÃO: Não se observou diferença na densidade mamária de mulheres com FOP comparativamente à de mulheres na pós-menopausa utilizando TH pelo mesmo período de tempo. Estes resultados podem auxiliar na aderência à TH de pacientes com FOP.
Тема - темы
Adult , Female , Humans , Middle Aged , Breast/drug effects , Estrogen Replacement Therapy/adverse effects , Postmenopause/drug effects , Primary Ovarian Insufficiency/drug therapy , Breast Neoplasms/etiology , Cross-Sectional Studies , Mammography , Pilot Projects , Risk FactorsРеферат
Premature ovarian failure (POF) is a common occurrence in women during their reproductive years. There is paucity of data on spontaneous ovulation and subsequent pregnancies in such women. In this report, we describe three women with POF, two of whom had spontaneous conceptions and the third resumed spontaneous regular menstrual cycles. All these women had received oestrogen-progesterone tablets for many cycles (ethyl oestradiol 0.05 mg and levonorgestrel 0.25 mg a day, 21 days a month). We speculate about the possibility of elevated gonadotrophins causing down regulation of gonadotrophin receptors and restoration of the sensitivity of the few remaining ovarian follicles by lowering of serum gonadotrophins with oestrogen therapy.
Тема - темы
Adult , Estradiol Congeners/therapeutic use , Ethinyl Estradiol/therapeutic use , Female , Humans , Levonorgestrel/therapeutic use , Primary Ovarian Insufficiency/drug therapy , Pregnancy , Progesterone Congeners/therapeutic useРеферат
A falência ovariana prematura é uma condiçäo caracterizada por amenorréia, infertilidade, deficiência dos hormônios sexuais e elevaçäo das gonadotrofinas em mulheres com idade inferior a 40 anos. Os autores relatam a ocorrência de uma gravidez em uma paciente de 32 anos portadora de amenorréia hipergonadotrófica, em uso de terapia de reposiçäo hormonal (TRH).
Тема - темы
Humans , Female , Adult , Pregnancy , Hormone Replacement Therapy , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/drug therapy , Menopause, Premature , Diabetes, Gestational , Pregnancy, High-RiskРеферат
Se presenta el cuadro de falla ovárica prematura de etiología inmunológica, describiendo sus características fisiopatológicas y clínicas, diagnóstico, tratamiento y pronóstico. Se reporta un caso clínico atendido en el Servicio de Ginecología y Obstetricia del Hospital San Juan de Dios, discutiendo alternativas diagnósticas y terapéuticas
Тема - темы
Humans , Female , Adult , Autoimmune Diseases/complications , Primary Ovarian Insufficiency/etiology , Amenorrhea/etiology , Hormone Replacement Therapy , Primary Ovarian Insufficiency/classification , Primary Ovarian Insufficiency/physiopathology , Primary Ovarian Insufficiency/drug therapy , Oophoritis/physiopathology , Signs and SymptomsРеферат
OBJETIVOS: Descrever os efeitos de um esquema de reposiçao hormonal cíclico em mulheres com falência ovariana precoce (FOP) sobre os níveis de gonadotrofinas e a morfologia endometrial. CASUISTICA E METODOLOGIA: Foram estudadas 12 mulheres com FOP e comparadas a 17 mulheres normais e ovulatórias. O regime de substituiçao consistiu de doses crescentes de valerato de estradiol, mimetizando uma elevaçao pré ovulatória e início de progesterona vaginal no dia 14 do ciclo, em doses crescentes. Foram dosados diariamente LH, FSH, estradiol e progesterona e realizado biópsia de endométrio no dia 21 do ciclo. RESULTADOS: as concentraçoes de LH e FSH permaneceram mais elevadas do que as concentraçoes médias de mulheres ovulatórias. Houve pico de LH e FSH em todas as pacientes, em torno do 14( dia do ciclo induzido. Os níveis de estradiol foram similares aos de um ciclo normal, havendo um aumento ao final da fase folicular e outro correspondendo ao meio da fase lútea. Os níveis de progesterona elevaram-se a partir do dia do pico de LH, com um perfil semelhante ao de um ciclo normal, porém com valores mais baixos (5 a 7 ng/ml). Os endométrios biopsiados no dia 21 foram sincrônicos, com adequada maturaçao estromal e glandular. CONCLUSOES: apesar de concentraçoes plasmáticas diferentes, o ciclo de substituiçao proposto foi capaz de promover um perfil endócrino e resposto endometrial compátiveis com um ciclo normal.
Тема - темы
Humans , Female , Adult , Endometrium/drug effects , Estradiol/pharmacology , Gonadotropins/blood , Primary Ovarian Insufficiency/drug therapy , Estrogen Replacement Therapy/methods , Estradiol/therapeutic use , Follicle Stimulating Hormone/blood , Luteinizing Hormone/bloodТема - темы
Humans , Male , Female , Pregnancy , Infant, Newborn , Adult , Estrogens/therapeutic use , Primary Ovarian Insufficiency/drug therapy , Ovulation Induction , Pregnancy , Estrogens/pharmacologyРеферат
El presente estudio: Falla Ovárica Prematura, se realizó retrospectivamente en el Hospital Nacional Cayetano Heredia, en el servicio de Endocrinología Ginecológica, durante los años 1980-1986. Se estudiaron 15 pacientes cuyas edades fluctuaron entre los 17 y 37 años, que habían presentado amenorrea, bochornos, sudoraciones, cefaleas y también adolecían de infertilidad primaria o secundaria. Dentro de los síntomas vasomotores encontramos que los bochornos fueron la manifestación más frecuente, 73.3 por ciento de los casos. Se realizaron determinaciones hormonales, encontrándose que en todas las pacientes los niveles de LH y FSH estuvieron incrementados en el rango de 40 a 100 mUI/ml, 80 por ciento para FSH y 86.7 por ciento para LH. Las otras pacientes tuvieron rangos hormonales mayores. Se realizó biopsia ovárica en 13 pacientes, encontrándose ausencia de folículos en 9 de ellas. En ningún caso se encontró infiltrado linfocitario. Se administró tratamiento con diversos esquemas: Estrógenos Progestágenos combinados, Estrógenos Progestágenos cíclicos, Estrógenos solos y Bromocriptina sola o combinada. Se obtuvieron respuestas positivas (menstruación) en 11 de las 13 pacientes que recibieron tratamiento; 2 pacientes se perdieron al seguimiento. Se obtuvo una gestación en una paciente, que además tenía niveles altos de prolactina y que recibió tratamiento con Bromocriptina y Clomifeno.