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A 24-year-old female with significant ovarian hypertestosteronism, who responded well both to gonadotropin releasing hormone (GnRH) agonist and cyclic administration of estrogen and gestagens in terms of suppressing circulating testosterone levels is reported. The patient's menstrual periods had been regular since menarche at the age of 12 until she became amenorrheic at the age of 20. She visited our facility in November 1988 after receiving three cycles of estrogen and gestagen replacement therapy from a previous physician which caused withdrawal bleeding. Clomiphen citrate reportedly failed to induce apparent ovulation. On her first visit with us, she was 160 cm tall weighing 47 kg with apparent hoarseness but not with hirsutism. Pelvic examination revealed significant clitoromegaly but otherwise normal external and internal genitalia. Laparoscopic examination disclosed that her uterus appeared to be normal with bilateral ovaries relatively small (4 x 4 x 3 cm) without tumorous or polycystic appearance. Histological examination of her ovaries obtained at laparoscopy showed several primary follicles with mild infiltration of the stromal cells. No thickened tunica albuginea or cystic formation were observed. These findings did not support either polycystic ovary or hyperthecosis. Serum testosterone (T) levels were extremely high (7.1 ng/ml), while serum androstenedione levels were only slightly above normal range (3.1 ng/ml). Urine 17-KS excretion was slightly increased (6.1 mg/day), while 17-OHCS output was within normal range (4.0 mg/day). Basal serum LH and FSH levels were within normal range and LH pulse frequency was reduced to 1 in 4 hours. Administration of dexamethasone 1 mg/day for 2 days did not suppress circulating T and free T levels but lowered serum cortisol concentration and urine excretion of 17-OHCS. Blood glucose and insulin levels were within normal limits and their responses to oral glucose administration were normal. Abdominal and pelvic ultrasonography and computed tomography as well as adrenal scintigraphy did not reveal any tumorous lesions in bilateral adrenals and ovaries. Administration of GnRH agonist, Buserelin 900 micrograms/day, suppressed circulating T concentrations to 0.7 ng/ml in 8 days, while it had no significant effects on DHEA and DHEA-S levels. After 16 weeks of Buserelin administration, ovulation was successfully induced by hMG administration. Cyclic estrogen and gestagen replacement therapy by Kaufmann's schedule for 2 cycles also suppressed serum T levels to normal, female range. Thus, the present case represents non-neoplastic, non-PCO, ovarian hypertestosteronism which responded well both to GnRH agonist and estrogen and gestagen replacement therapy in terms of lowering circulating T levels.

Our previous work showed that melatonin (N-acetyl-5-methoxytryptamine) inhibits proliferation of the human endometrial cancer cell line, Ishikawa, which is estrogen receptor-positive. The aim of the present study was to determine whether Ishikawa cells possess membrane melatonin receptors. Binding of the radioligand 2-[125I]-iodomelatonin to membrane preparations obtained from Ishikawa cells was detectable, saturable and stable. Scatchard analysis revealed that the dissociation constant (Kd) of the binding sites was 179.0 pm (similar to that of the MT2 [Mel1b] melatonin receptor subtype), and that the concentration (Bmax) of the binding sites was 12.9 fmol/mg protein. Luzindole, a selective MT2 melatonin receptor antagonist, significantly suppressed binding of 2-[125I]-iodomelatonin at all concentrations tested (10(-8) to 10(-4) m). These results suggest that the MT2 melatonin receptor subtype is present in the membranes of Ishikawa cells, and that the antiproliferative effect of melatonin on Ishikawa cells is mediated via the MT2 receptor. This may have implications for the use of melatonin in endometrial cancer therapy.

Brain metastases of gynecological malignancies are rare, but the incidence is increasing. Patients with brain metastases have a poor prognosis, therefore early detection and optimal management is necessary. In order to determine a new biomarker, we aimed to identify proteins that associated with brain metastases. We investigated proteins associated with brain metastases of gynecological malignancies in three patients who underwent surgical resection (stage IIb cervical cancer, stage Ib endometrial cancer, and stage IIIb ovarian cancer). Proteomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples of the primary tumors and brain metastases, which were analyzed by liquid chromatography with tandem mass spectrometry. Thereafter, candidate proteins were identified by the Scaffold system and Mascot search program, and were analyzed using western blotting and immunohistochemistry. As a result, a total of 129 proteins were identified. In endometrial and ovarian cancers, western blotting revealed that the expression of alpha-enolase (ENO1) and triosephosphate isomerase (TPI-1) was higher and the expression of Transgelin-2 (TAGLN2) was lower in metastatic tumors than in primary tumors. On the other hand, the expression of TPI-1 and TAGLN2 was lower in metastatic tumors than in primary tumors in cervical cancer. Immunohistochemistry confirmed that ENO1 expression was elevated in the metastatic tumors compared with the primary tumors. In conclusion, the present study showed that FFPE tissue-based proteomics analysis can be powerful tool, and these findings suggested that ENO1, TPI-1, and TAGLN2 may have a role in the development and progression of brain metastasis from gynecological malignancies.

Fertility issues should be addressed to all patients in reproductive age before cancer treatment. In men, cryopreservation of sperm should be offered to all cancer patients in reproductive age regardless of the risk of gonadal failure. In women, the recommendation of fertility preservation should be individualized based on multiple factors such as the urgency of treatment, the age of the patient, the marital status, the regimen and dosage of cancer treatment.

Background Patients with gynecologic cancer have a high risk of venous thromboembolism (VTE) like patients with other cancers. However, there is little information on risk factors for VTE during gynecologic surgery and no uniform preventive strategy. Our objectives were to identify risk factors for perioperative VTE in gynecologic patients and establish methods for prevention. Methods We analyzed 1,232 patients who underwent surgery at the Department of Obstetrics and Gynecology of St. Marianna University School of Medicine between January 2005 and June 2008. We investigated (1) risk factors for preoperative VTE, (2) use of an inferior vena cava (IVC) filter, and (3) risk factors for postoperative VTE. Results There were 39 confirmed cases of perioperative VTE (3.17%), including 25 patients with preoperative VTE and 14 with postoperative VTE. Thirty-two patients had cancer and seven patients had benign diseases. Twenty-two of the 32 cancer patients (68.7%) had preoperative VTE, while postoperative VTE occurred in 10 cancer patients. Multivariate analysis indicated that ovarian cancer, tumor diameter ≥10 cm, and previous of VTE were independent risk factors for preoperative VTE. Among ovarian cancer patients, multivariate analysis showed that an age ≥50 years, the presence of heart disease, clear cell adenocarcinoma, and tumor diameter ≥20 cm were independent risk factors for preoperative VTE. The factors significantly related to preoperative VTE in patients with benign disease included previous VTE, age ≥55 years, tumor diameter ≥20 cm, and a history of allergic-immunologic disease. Thirteen of the 25 patients (52%) with preoperative VTE had an IVC filter inserted preoperatively. Postoperative screening (interview and D-dimer measurement) revealed VTE in 14/1,232 patients (1.14%). Multivariate analysis indicated that cancer surgery, a history of allergic-immunologic disease, and blood transfusion ≥2,000 ml were independent risk factors for postoperative VTE. Conclusions Perioperative VTE is often fatal and preventive measures should be taken in the gynecologic field, especially when patients have the risk factors identified in this study. Since VTE is often present before surgery, preoperative screening is important and use of an IVC filter should be considered.