Women with polycystic ovary syndrome have elevated serum concentrations of and altered GABA(A) receptor sensitivity to allopregnanolone.

OBJECTIVE: Several studies have reported that γ-aminobutyric acid (GABA) ergic circuits are involved in the pathophysiology of polycystic ovary syndrome (PCOS). The progesterone metabolite allopregnanolone is a potent GABA(A) -receptor-modulating steroid, and patients may have increased concentrations of allopregnanolone or altered GABAA receptor sensitivity. We investigated both of these possibilities in this study. PATIENTS: We enrolled 9 women with PCOS and 24 age-matched eumenorrhoeic controls, who were divided into two groups by body mass index (BMI) (16 normal weight and 8 overweight). MEASUREMENTS: We investigated the effects of allopregnanolone injection on GABA(A) receptor sensitivity in both groups of women. All women received a single intravenous dose of allopregnanolone (0·050 mg/kg). GABA(A) receptor sensitivity was assessed with the saccadic eye velocity (SEV) over 30° (SEV30°), the SEV30°/allopregnanolone concentration ([Allo]) ratio, and sedation, which were measured together with serum allopregnanolone at intervals for 180 min after injection. The controls were tested in the follicular phase of the menstrual cycle. RESULTS: Baseline allopregnanolone concentrations were higher in the PCOS women than in the normal-weight (P = 0·034) and overweight controls (P = 0·004). The allopregnanolone concentrations after injection were higher in the PCOS women (P = 0·006) and overweight controls (P = 0·037) than in the normal-weight controls. All groups showed a decline in the SEV30°/[Allo] ratio after injection. Allopregnanolone had a smaller effect on the SEV30°/[Allo] ratio in the overweight women (PCOS, P = 0·032; controls, P = 0·007) than in the normal-weight controls. The sedation score after allopregnanolone injection was lower in the PCOS patients than in the controls, but was not different between the two control groups. CONCLUSIONS: PCOS women had elevated baseline allopregnanolone concentrations compared with follicular-phase controls. All overweight women (PCOS and controls) were less sensitive to allopregnanolone than normal-weight controls.

Long-Term Follow-Up of Tamoxifen Treatment and the Use of Imaging in Psammocarcinoma: A Case Report, Review of the Literature and Discussion of Diagnostic and Therapeutic Challenges.

Psammocarcinoma (PsC) represents a rare form of low-grade serous tumor of the ovary or peritoneum. Although ovarian cancer generally has a poor prognosis in its late stages, PsC seems to have a more indolent course. We present a patient with a history of unspecific abdominal pain for more than a year, with sudden acute onset of severe inguinal pain. On admission to the hospital, a computed tomography (CT) revealed a pelvic mass of suspected ovarian origin. Radical surgery was attempted but not achieved due to widespread tumor growth. Histopathological evaluation revealed estrogen receptor-positive stage III PsC. Tamoxifen treatment was thus initiated, still maintaining stable disease 10 years later. The patient has undergone extensive radiological work-up, including CT, chest X-ray, 18F-fluoro-deoxy-glucose positron emission tomography (PET)/CT, 99mTc- hydroxymethylene diphosphonate (HDP) bone scintigraphy, 18F-fluoro-thymidine (FLT) PET/CT, Tc-99m depreotide scintigraphy and magnetic resonance imaging. In conclusion, we demonstrate that PsC has characteristic radiological features and different imaging modalities can be suitable in different clinical situations. In contrast to most other ovarian cancers, PsC does not always warrant adjuvant chemotherapy, even in advanced stages. This emphasizes the need for a deeper knowledge of the biological behavior of this rare tumor, to select the optimal treatment strategy.