Metformin improves polycystic ovary syndrome and activates female germline stem cells in mice / 生理学报

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E2 levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.

Ovarian tumors with elevated ca-125 levels and severe juvenile hypothyroidism: A need for increased awareness.

A 15-yr-old girl presented with bilateral gross ovarian tumors, clinical features of long-standing unrecognized hypothyroidism and markedly elevated CA-125 levels. Ovarian resection was avoided, as the presentation was consistent with the Van Wyk and Grumbach syndrome; and the patient was treated with replacement of thyroid hormone. Regression of the ovarian tumors occurred 6 months after initiation of the treatment. The authors emphasise the need for increased awareness and screening for hypothyroidism in patients with ovarian tumors, in order to prevent inadvertent operative interventions.

Treatment of autonomous ovarian follicular cyst with long-term anastrozole therapy.

Functional follicular ovarian cysts are frequently reported in girls with peripheral precocious puberty (PP). These cysts are usually self-limiting and resolve spontaneously. Several drugs like antiestrogens (tamoxifen) and new aromatase inhibitors are seldom used for treatment. Here we report a girl with peripheral PP who presented with unilateral enlargement of the ovary and a recurrent autonomous ovarian cyst. No skin pigmentation or bone anomaly was noted. The patient was successfully treated with anastrozole, a highly selective aromatase inhibitor. No adverse reaction was noted. Anastrozole is a safe and tolerable drug especially used to suppress estrogen action.

Massas anexiais na gestação / Adnexal masses in pregnancy

O advento da ultrassonografia (US) durante o pré-natal tem contribuído para o aumento da detecção de massas anexiais na gestação. A maior parte dos tumores tem resolução espontânea por volta da 16ª semana de gestação, sendo associada a cistos funcionais. Massas que persistem após esse período podem acarretar riscos de torção, ruptura e obstrução do canal de parto, necessitando, muitas vezes, de uma intervenção cirúrgica de emergência. A ocorrência de tumores malignos é rara. Além da US, que é utilizada como primeira modalidade para o diagnóstico, o estudo do CA-125 e do B-hCG deve ser realizado. Esses marcadores estão normalmente aumentados durante a gestação. No entanto, na presença de massas tumorais, os níveis são bem mais alterados. O manejo dessa patologia na gravidez é desafiante para o médico e acarreta ansiedade para a paciente. A cirurgia, quando indicada, deverá ser realizada entre o segundo e terceiro trimestres da gestação, levando-se em conta os riscos de complicações para a mãe e o feto. Estudos mostram que, havendo indicações precisas de tratamento adjuvante na gravidez, seu uso não deve ser adiado, pois, em longo prazo, o prognóstico para fetos expostos à quimioterapia intra-útero parece ser bom.

The advent of routine prenatal ultrasonography (US) has increased the detection of adnexal masses during pregnancy. The majority of tumors spontaneously resolve around the 16ª week of gestation, usually being associated with functional cysts. Masses that last after this period can complicate on risks of torsion, rupture of obstruction of labor, requiring emergent surgical intervention. The prevalence of malignant tumor is rare. Besides the use of US, which is the primary diagnostic modality, the study of tumor markers, such as CA-125 and B-hCG, must be done. Their levels are already elevated during pregnancy. However, in the presence of certain types of tumors, these levels are much more altered. The management of this pathology during pregnancy is quite challenging to the medical team and involves psychological issues to the patient. When indicated, the surgery must be taken place between the second and third trimester, always considering the risks of complications to the mother and the fetus. Several studies report that if there are strong indications for adjuvant therapy, it should not be delayed, because the longterm fetal outcomes appear to be good for those fetuses exposed to chemotherapy in utero.

¿Son útiles los anticonceptivos orales en el tratamiento de los quistes ováricos funcionales? / Usefulness of oral contraceptives in the treatment of functional ovarian cysts

Objetivos: Determinar si los preparados de estrógenos y progestágenos orales, usados ampliamente en la práctica clínica, son realmente útiles en el manejo de quistes ováricos con características de benignidad en la ecografía transvaginal. Método: Se realizó una búsqueda detallada en bases de datos electrónicas de uso frecuente. Dos de los artículos encontrados cumplían con los criterios de inclusión. Resultados: Mackenna y cois trabajaron con un total de 50 mujeres con quistes funcionales inducidos farmacológicamente. Dividieron en forma aleatoria a las pacientes en dos grupos. Uno de ellos recibió anticonceptivos orales y el otro no. No se encontraron diferencias significativas en el tiempo de desaparición de las lesiones a la ecografía entre ambos grupos. Bayar y cois, siguieron a 141 mujeres en edad fértil que presentaban quistes simples en la ecografía. Conformaron dos grupos. El primero se manejó con anticonceptivos orales y el segundo de manera expectante. En ese estudio no se encontraron diferencias significativas en la reducción del tamaño de los quistes en el tiempo al comparar ambos grupos. Conclusiones: Sería adecuado que el médico al enfrentarse a mujeres premenopáusicas con quistes simples, considerase inicialmente el manejo conservador por al menos dos meses y luego evaluase la persistencia o desaparición de éstos con estudio de imágenes.

Objective: To establish if oral contraceptives composed by estrogens and progestogens are useful in the management of ovarian cysts that appear benign in transvaginal ultrasound. Method: A detailed search was performed in electronic data bases. Two of the articles found met the inclusion criteria. Results: Mackenna and cols, worked with fifty women with functional ovarian cysts pharmacologically induced. They divided their patients randomly in two groups. One of them received oral contraceptives and the other did not. There were no significant differences between the groups in the time of disappearance of the lesions in ultrasound. Bayar and cols, studied 141 fertile women with simple ovarian cysts in ultrasound. One group received oral contraceptives and the other did not. In this study there were no significant differences between groups in the reduction of the size of the cysts over time. Conclusions: In premenopausic women with simple ovarian cysts it would be adequate to considerate expectant management initially for at least two months.

Comparison of low-dose monophasic oral contraceptive pills and expectant management in treatment of functional ovarian cysts.

OBJECTIVE: To compare the effectiveness of low-dose monophasic oral contraceptive pills in the treatment of spontaneously occurring functional ovarian cyst detected by ultrasonography compared with expectant management. MATERIAL AND METHOD: A total of 70 women in their reproductive period with functional ovarian cysts detected by means of ultrasonography were randomized to low-dose monophasic Oral Contraceptive pills (OC) or to expectant management and followed up at one month with a second ultrasonography. If the ovarian cysts were still present, the women were followed for another month while on the same treatment. RESULTS: At the first month, the remission rates of ovarian cyst were 63.6% in low-dose monophasic OC and 52.9% in expectant groups. At the second month, the cumulative remission rates increased up to 72.7% in low-dose monophasic OC and 67.6% in expectant groups. There was no statistically significant difference between the two groups at both the first and second month of treatment. The most common side effect in women using OC was acne (18%). CONCLUSION: Low-dose monophasic OC were no more effective than expectant management in the treatment of spontaneously occurring functional ovarian cysts.

Tumor ovárico en la postmenopausia consideraciones sobre su manejo / Ovarian tumor in the postmenopause considerations on its handling

Se presenta una serie de 234 pacientes postmenopáusicas mayores de 50 años con diagnóstico de tumor ovárico operadas en nuestro centro. Aproximadamente 60 por ciento de los casos fueron hallazgo del examen, ecografía o de la cirugía. Las pacientes fueron mayoritariamente abordadas por laparotomía (89 por ciento). Sólo en 25 casos se realizó laparoscopia no registrándose casos de tumor maligno. En un 23 por ciento de los casos el diagnóstico histológico fue el de cáncer de ovario. En aquellos casos en que se realizó biopsia contemporánea (72,6 por ciento) hubo excelente concordancia (98,8 por ciento) con el diagnóstico reportado en la biopsia definitiva. La tasa de complicaciones observada fue menor al 10 por ciento (con menos de un 5 por ciento de complicaciones graves). De interés resulta el que no se observaron tumores malignos en lesiones ováricas con diámetro ultrasonográfico menor de 3 cm. Los hallazgos encontrados sugieren que el tumor ovárico en la postmenopausia no debe ser una indicación perentoria de cirugía abierta. El seguimiento ecográfico es factible en lesiones pequeñas (menores de 3 a 5 cm), particularmente si las características ecográficas sugieren benignidad y el CA-125 es negativo. Dada la frecuencia de tumores benignos, en casos bien seleccionados (por tamaño, características ecográficas y marcadores) y contando con biopsia contemporánea es posible realizar un abordaje por laparoscopia. En centros especializados la edad avanzada (> 70 años) no debiese ser una contraindicación a la cirugía.

A funçäo ovariana na síndrome de McCune-Albright: uma autonomia questionada / The ovarian function in McCune-Albright syndrome: a questionable autonomy

A síndrome de McCune-Albright faz parte do diagnóstico etiológico da puberdade precoce e está associada à formaçao de cistos ovarianos, displasia fibrosa óssea e manchas cutâneas hiperpigmentadas. Outras endocrinopatia podem estar presentes levando à hiperfunçao de tiróide, paratiróide e adrenal, além de hipersecreçao de hormônio do crescimento e prolactina. A sua exata fisiopatologia nao está esclarecida, porém tem sido admitida a ocorrência de hiperfunçao glandular múltipla e autônoma decorrente da expressao inadequada da adenilciclase nos órgaos envolvidos. Contrariando a hipótese de autonomia ovariana inicial e reversível após a puberdade, relatamos o acompanhamento longitudinal, por 20 anos, de uma paciente portadora da síndrome cujo controle da hiperfunçao ovariana na infância e involuçao dos cistos ovarianos de repetiçao, na vida adulta, sempre foram conseguidos com o bloqueio da secreçao das gonadotrofinas, seja com progestágenos, seja com superanálogos do LHRH.

Comportamento dos tumores císticos do ovário após conduta expectante e tratamento hormonal / Behavior of cystic tumor of the ovary after expectant management and hormonal treatment

Com a finalidade de determinar o comportamento dos tumores císticos do ovário diagnosticados e acompanhados pelo exame ginecológico e ultra-sonográfico, analisaram-se pacientes com cisto de 30 a 49mm (grupo I) e com cisto de 50 mm ou mais de diâmetro (grupo II). O tratamento clínico incluiu conduta expectante, associaçäo estrógeno-progestágeno ou progestágeno isolado. Comprovou-se regressäo do cisto em 84,6% das pacientes do grupo Isubmetidas a conduta expectante, o mesmo acontecendo com 83,3% do II; em 85,4% das do primeiro grupo que receberam associaçäo estrógeno-progestágeno e em 88,9% do segundo que receberam semelhante medicamento; 92,5% das do grupo I e em 93,1% das do II que fizeram uso de progestágeno isolado. Concluiu-se que a administraçäo desses esteróides näo influi na taxa de regressäo dos cistos de ovário tidos como funcionais, menores, iguais ou maiores que 50 mm de diâmetro

Shrinkage of recurrent endometrioma, after danazol.

A 29-year-old woman presented with a history of primary infertility one year after excision of endometrioma of the left ovary. On the first pelvic examination at the Infertility Clinic, the uterus was of normal size, retroversion and rather fixed with 0.5 cm firm nodule at its posterior surface. There was a tense cystic mass about 4-5 cm at the right adnexa. Three months later this mass was noted to have increased in size and the ultrasound revealed a slight, thick wall cystic mass with the largest diameter of 7 cm. The impression was endometriotic cyst of the right ovary. The patient was put on danazol 200 mg daily. After 6 months of treatment, the right ovarian mass was found to be 3.3 cm in the largest diameter by ultrasound. So the medication was discontinued. The patient conceived on the third cycle after discontinuing danazol. A healthy male infant, birth weight 3,320 g was delivered by elective cesarean section at term.