Genetic variations within the insulin gene region are associated with accelerated fetal growth.

Size at birth has been proposed to be associated with the risk of type 2 diabetes and cardiovascular disease later in life. It is, however, unclear whether this association is attributed to an unfavorable intrauterine environment or to specific genotypes predisposing both altered fetal growth and common diseases in adult life. The aim of this study was to investigate the associations between the neonatal birth size and the genotypes of polymorphic loci within the insulin gene (INS) region, which is susceptible to diabetes mellitus. We analyzed the genotypes of two polymorphic loci; -23HphI and HUMTH01, in 520 pairs of normal Japanese mothers and their neonates, and compared with the somatoscopic characteristics at birth converted into standard deviation scores (SDS) according to sex, parity and gestational weeks at delivery. It was revealed that neonatal -23HphI T allele and HUMTH01 allele10, which are linked to the INS variable number of tandem repeats (VNTR) class III allele, were associated with increased weight, head circumstance, and length at birth. These associations confirmed that variation within the INS region, most probably at the INS-VNTR, influences fetal growth. Furthermore, the finding that the paternally transmitted -23HphI T allele was exclusively correlated with increased size at birth indicates the involvement of an imprinting mechanism. In conclusion, the INS-VNTR class III allele might accelerate fetal growth in a parent-specific manner.

Recent changes of the incidence of complete and partial mole in Chiba prefecture.

AIMS: To study the changes of the incidence of complete mole (CM) and partial mole (PM) by 10-year age groups in Chiba Prefecture. METHODS: All women registered as CM and PMs in Chiba Prefecture during these 18 years were included in this study. The diagnosis of CM and PM was based on the macroscopic and/or microscopic findings. The annual numbers of pregnancy were obtained from the Division of Statistics in Chiba Prefecture Government. RESULTS: The incidence of CM at the upper and lower extremes of maternal age is higher than that of PM. The incidence of CM has decreased constantly at all maternal ages and significantly decreased in women of middle reproductive age (20-39 years old) since 1991, while that of PM has stayed constant during these 18 years. CONCLUSIONS: The incidence of CM and PM in Chiba Prefecture has become as low as that in Europe or the USA. These recent changes suggest that Japanese women may have lost the increased risk to ovulate a nuclear or inactive oocytes, or the differential diagnosis between CM and PM may be obscured with the macroscopic and/or microscopic findings.

Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and review of the literature.

OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by pituitary gonadotroph macroadenoma, and include a review of the literature. CASE REPORT: A 27-year-old woman presented with irregular menstruation and bilateral multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were marginally elevated for the follicular phase but within the physiological range. Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging disclosed a pituitary macroadenoma. Immunohistochemical examination of the surgically removed adenoma showed intense reactivity for FSH and LH. After the operation, E(2), LH and PRL levels were normalized, the ovaries returned to a normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A review of the literature showed that ovarian hyperstimulation caused by pituitary gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL and E(2) and low LH were reported in the majority of the cases, but E(2) may stay within the range observed in normal menstrual cycles.

Amino acid changes during successful pregnancy in a case of lysinuric protein insufficiency.

Lysinuric protein insufficiency (LPI) is a rare autosomal recessive disorder, and pregnancy in patients with this condition has been considered risky. We, however, observed a relatively favorable course of pregnancy in a woman with LPI, and even amelioration of symptoms during pregnancy. We believe that this unique observation is not only important for patients with LPI who are facing a choice of child-bearing, but is also of interest to obstetricians and researchers of amino acid metabolism.

Genetic origin and imprinting in hydatidiform moles. Comparison between DNA polymorphism analysis and immunoreactivity of p57KIP2.

OBJECTIVE: To evaluate whether p57KIP2 expression is concordant with the result of DNA polymorphism analysis in molar pregnancy. STUDY DESIGN: Eleven molar pregnancies diagnosed by pathologic findings between October 2002 and April 2004 were studied. Histopathologic diagnosis, DNA polymorphism analysis and p57KIP2 immunohistochemistry were investigated. RESULTS: DNA polymorphism analysis identified 3 biparental conceptuses as well as 4 dispermic androgenetic complete moles (CMs) and 4 suggestive monospermic CMs. Distinctly positive nuclear immunoreactivity of p57KIP2 was observed in a significant proportion of the villous cytotrophoblast and mesenchyme (30-60% of cells positive) in 3 cases of biparental conceptuses proven by DNA polymorphism. In contrast, p57KIP2 expression was negative (< 5% positive cells) in either the villous cytotrophoblast or mesenchyme in 8 cases of androgenetic conceptuses proven by DNA polymorphism. In all 11, p57KIP2 immunostaining was observed in the nuclei of extravillous trophoblasts that served as internal positive controls. CONCLUSION: Negative p57KIP2 immunoreactivity (paternally imprinted, maternally expressed gene) was in perfect concordance with the androgenetic origin of molar pregnancies proven by DNA polymorphism. The results suggest that p57KIP2 immunoreactivity, which can be performed in routine pathologic examinations, is a promising ancillary diagnostic tool to differentiate androgenetic CM from biparental conceptuses.

Accelerated bone turnover in pregnant women with McCune-Albright syndrome.

Bone turnover in pregnant women with McCune-Albright syndrome may be affected by both the syndrome and pregnancy. This study evaluated changes in biochemical bone turnover markers in pregnant women with the syndrome. Serum calcium, phosphorus, 1,25-dihydroxyvitamin D (1,25-(OH)2D), intact osteocalcin (I-OC) and alkaline phosphatase (ALP), and urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and hydroxyproline (HPR) were measured during pregnancy and postpartum in 2 women with McCune-Albright syndrome. Serum calcitonin (CT), and plasma intact parathyroid hormone (I-PTH) and parathyroid hormone-related protein (PTHrP) were also measured in 1 patient. Serum corrected Ca levels were normal or low-normal; phosphorus levels were normal, and 1,25-(OH)2D levels increased toward term and decreased thereafter, similar to normal pregnant women. Urinary Pyr, D-Pyr and HPR were elevated during pregnancy compared to normal pregnant women, peaked just after delivery, and decreased thereafter. Serum I-OC and ALP levels were high during pregnancy and postpartum. Intact PTH levels were increased during pregnancy and postpartum compared to normal pregnant women, whereas serum CT and PTHrP levels were not elevated. Both bone formation and absorption appear to be more enhanced during pregnancy and postpartum in women with McCune-Albright syndrome than in normal pregnant women. Additional or amplified cyclic AMP synthesis in bone cells through activation of the alpha subunit of G protein, independent of hormonal control, may explain the high local bone turnover.

Relapse rate of patients with low-risk gestational trophoblastic tumor initially treated with single-agent chemotherapy.

OBJECTIVE: To determine the factors for relapse in patients with low-risk gestational trophoblastic tumor (GTT) treated with single-agent chemotherapy. METHODS: Between 1974 and 2000, 272 consecutive patients with low-risk GTT were initially treated with methotrexate (MTX), actinomycin D (Act-D) or etoposide chemotherapy. The primary remission rate, change of chemotherapy because of drug resistance or toxicity, and relapse rate were compared. RESULTS: Overall survival rate and primary remission rate for 272 patients were 100% and 75.7%, respectively. Primary remission rate was significantly higher in patients given etoposide than those given conventional MTX (P < 0.0001) or MTX-folinic acid (MTX-CF) (P = 0.0005). Twenty-four (8.8%) patients required a change of chemotherapy because of drug resistance. The frequency of drug resistance was significantly higher in patients treated with MTX-CF than those treated with etoposide (P = 0.006). Although maternal age, presence of metastasis, high pretreatment hCG titer, and planned hysterectomy did not influence the development of drug resistance, the new FIGO scores were significantly higher in patients who developed drug resistance. Relapse rate increased significantly in patients who had high FIGO scores and who required change of chemotherapy due to drug resistance. CONCLUSIONS: All patients with low-risk GTT eventually attained complete remission, even though some developed drug resistance to the first-line chemotherapy. The relapse rate was significantly higher in patients with drug resistance than those with primary remission. Chemotherapy regimen that induces little drug resistance is desirable from the viewpoint of long-term prognosis.

Successful pregnancy and delivery after removal of gonadotrope adenoma secreting follicle-stimulating hormone in a 29-year-old amenorrheic woman.

We report a case of ovarian hyperstimulation related to a gonadotroph adenoma in a 29-year-old woman. The patient presented with amenorrhea and large cystic ovaries. Her serum estradiol was markedly elevated (up to 31,100 pmol/l). Serum LH was low, but serum FSH and PRL were normal. Cranial magnetic resonance imaging study revealed a pituitary macroadenoma. After successful removal of the pituitary tumor, FSH, LH and estradiol normalized and fluctuated within normal ranges thereafter. The patient resumed regular cycles of menstruation and conceived spontaneously. During pregnancy, estradiol increased and FSH and LH decreased. The finding confirms restoration of negative feedback of estradiol on FSH and LH secretion. The pregnancy course was uneventful and enlargement of ovaries did not occur.

Serum vascular endothelial growth factor (VEGF) and VEGF-C levels as tumor markers in patients with cervical carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) and VEGF-C play a crucial role in the regulation of tumor growth and metastasis. The current study examined the significance of serum VEGF and VEGF-C levels in relation to conventional clinicopathologic parameters, response to treatment, and survival in patients with cervical carcinoma. METHODS: Between December 1999 and March 2004, serum VEGF and VEGF-C levels were analyzed in 78 patients with cervical carcinoma undergoing primary treatment (primary surgery [n=40] and radiotherapy [n=38]), as well as in 30 healthy controls. Serum VEGF and VEGF-C levels were assessed by enzyme-linked immunosorbent assay before and within 2 weeks after treatment. RESULTS: Serum VEGF and VEGF-C levels were higher in patients with cervical carcinoma than in the healthy control (P=0.0002 and P=0.0007, respectively). Both VEGF and VEGF-C concentrations increased significantly in patients with squamous cell carcinoma (SCC vs. normal control: P<0.0001 and P=0.0001, respectively), but not in adenocarcinoma (vs. normal control: P=0.2982 and P=0.7766, respectively). In an analysis of SCC, the pretherapeutic serum levels of VEGF and VEGF-C correlated significantly with advanced International Federation of Gynecology and Obstetrics stage and large tumor size, but not with lymph node metastasis. The pretherapeutic serum level of VEGF-C also correlated significantly with disease recurrence or persistence after treatment. Both serum VEGF and VEGF-C levels decreased significantly after treatment. CONCLUSIONS: The serum levels of both VEGF and VEGF-C have potential usefulness as biologic markers of SCC of the uterine cervix.

Advances in the clinical laboratory detection of gestational trophoblastic disease.

BACKGROUND: Gestational trophoblastic disease (GTD) consists of a spectrum of disorders that are characterized by an abnormal proliferation of trophoblastic tissue. Gestational trophoblastic neoplasia (GTN) refers to a subset of GTD with a persistently elevated serum hCG in the absence of a normal pregnancy and with a history of normal or abnormal pregnancy. Although previously a lethal disease, GTN is considered today the most curable gynecologic cancer. However, a delay in the diagnosis may increase the patient's risk of developing malignant GTN, and therefore the prompt identification of GTN is important. SERUM MARKERS: hCG test is essential for detection of GTN. It has emerged that there are problems with hCG tests. In addition to regular hCG, at least five major variants of hCG are present in serum samples. False-positive hCG (phantom hCG) can occur in the absence of GTN. Low-level real hCG may occasionally persist in the absence of clinical evidence of pregnancy or GTD. Alternatively, low-level real hCG may be due to pituitary hCG. Other placental hormones, human placental lactogen (hPL), inhibin and activin, and progesterone have also been evaluated as tumor markers for GTD. CONCLUSION: hCG has high diagnostic sensitivity, approaching 100% sensitivity, for managing the treatment of GTN and for detecting recurrences of disease. It is recommended to use hCG test that recognizes all forms of the hCG molecule. In cases where low-level hCG persists, it must be differentiated whether it is real or false. Real-hCG may be due to quiescent gestational trophoblastic disease or pituitary hCG. It has not yet been established whether measurement of markers other than hCG (hPL, inhibin, activin, and progesterone) is useful in the detection and follow-up of GTD.

Quantitative and qualitative evaluations of fetal lung with MR imaging.

PURPOSE: To measure both volume and signal intensity of the fetal lung at magnetic resonance (MR) imaging and to evaluate the clinical use of this method to predict fetal pulmonary hypoplasia. MATERIALS AND METHODS: A total of 87 fetuses evaluated with MR imaging at 24-39 weeks of gestation were classified into a control group with good respiratory outcome (group A, n = 58) or a poor outcome group with severe respiratory disturbance after birth (group B, n = 29). Planimetric measurement of total lung volume and calculation of the ratio of lung signal intensity to spinal fluid signal intensity (L/SF) were performed on MR images by using region-of-interest analysis. Regression analysis, analysis of covariance, analysis of variance, and receiver operating characteristic (ROC) analysis were performed. RESULTS: The best fit for group A lung volume was represented by the regression line V = (2.41 x G) - 37.6 (r = 0.537, P <.001), in which V is lung volume and G is gestational weeks; that for group B, by V = (0.97 x G) - 14.0 (r = 0.378, P <.05). Results of analysis of covariance with gestational weeks used as a covariate showed a significant difference in lung volume between the two groups (P <.001). Mean +/- SEM for L/SF ratio was 0.817 +/- 0.013 and 0.598 +/- 0.019 in groups A and B, respectively (P <.001). For prediction of postnatal respiratory outcome, the area under the ROC curve for lung volume and L/SF ratio combined was 0.990, significantly higher than that for lung volume alone (P <.05). CONCLUSION: Simultaneous measurement of fetal lung volume and signal intensity on MR images is a promising method for predicting fetal pulmonary hypoplasia.

Multi-minicore disease with susceptibility to malignant hyperthermia in pregnancy.

Multi-minicore disease (MmD) is a congenital non-progressive or slowly progressive myopathy associated with multifocal degeneration of muscle fibers. Obstetric management for patients with MmD has not been described previously. A 25-year-old primigravida with a history of muscular weakness from birth was diagnosed with MmD and found to be susceptible to malignant hyperthermia (MH) by muscle biopsy at 28 weeks of gestation. Pregnancy proceeded uneventfully and she had a successful vaginal delivery under sufficient preparation for the possible occurrence of MH. Pregnant women who exhibit myopathic symptoms from childhood should consult an anesthesiologist prior to delivery.

Criteria for initiating chemotherapy in patients after evacuation of hydatidiform mole.

OBJECTIVES: To evaluate the spontaneous regression curve of serum human chorionic gonadotropin (hCG) in patients with an uneventful course after evacuation of hydatidiform mole and to compare the criteria for initiating chemotherapy in patients after evacuation of mole. METHODS: From 1986 to 2001, 608 patients were followed at our department after evacuation of mole. The spontaneous regression curves of serum hCG in 432 patients with an uneventful course were established. RESULTS: After evacuation of mole, the titers of serum hCG decreased constantly, and 90% of patients with an uneventful course were within normal range within 16 weeks. In 432 patients with an uneventful course, the upper 95% confidence limit of serum hCG at 5, 8 and 20 weeks was 753.7, 422.9 and 14.8 mIU/ml, respectively. Moreover, 39 (9.0%) and 15 patients (3.5%) with an uneventful course might have been diagnosed with gestational trophoblastic tumor and received needless chemotherapy based on the normal regression curve established by the Japan Society of Obstetrics and Gynecology or the US criteria of 4 consecutive plateauing or rising hCG values, respectively. CONCLUSIONS: Our more selective criteria for initiating chemotherapy in patients after evacuation of mole, i.e. hCG of 10,000 mIU/ml at 5 weeks, 1,000 mIU/ml at 8 weeks and nondetectable levels at 24 weeks after evacuation of mole, may be safe and acceptable in the management of patients after evacuation of mole.

Placental mesenchymal dysplasia initially diagnosed as partial mole.

Placental mesenchymal dysplasia is a rare condition of pregnancy that presents as macroscopic features of molar change in the placenta and normal karyotype fetus. These cases are often misdiagnosed as partial mole. We report a new case of mesenchymal dysplasia. A 27-year-old Japanese primigravida delivered an 820 g female baby (46XX karyotype) without congenital anomalies at 27 weeks gestation due to massive bleeding with placenta previa. The placenta had mimicking partial moles, grape-like vesicles and normal villi that diffusely occupied the area on the maternal surface of the placenta. Pathologically, enlarged stem villi contained loose, moderately cellular connective tissue with focal cistern-like formation, and peripherally located vessels. Abnormal trophoblastic proliferation and trophoblastic inclusions were not observed in any of the sections examined. Some villi contained chorioangiomatoid changes. The mother and child were followed up for more than 5 years and showed no sign of trophoblastic disease or Beckwith-Wiedemann syndrome features.

Detection of epidermal growth factor receptor mRNA in peripheral blood of cervical cancer patients.

OBJECTIVE: Epidermal growth factor receptor (EGFR) has been reported to be expressed by immunohistochemistry in invasive cervical cancers. We evaluated the feasibility of detecting EGFR mRNA by EGFR-based reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood of patients with cervical cancer. METHODS: Expression of EGFR mRNA, cytokeratin (CK)-19 mRNA, and CK-20 mRNA was examined by RT-PCR in 12 human cervical cancer cell lines. All 12 cell lines expressed both EGFR mRNA and CK-19 mRNA, but only 4 of 12 (33.3%) cell lines expressed CK-20 mRNA. Peripheral blood samples from 20 healthy donors and 45 cervical cancer patients were also examined. RESULTS: In peripheral blood from 20 healthy donors, neither EGFR mRNA nor CK-20 mRNA was expressed, but CK-19 mRNA was expressed in 13 of 20 (65%). In contrast, EGFR mRNA was expressed in 12 of 45 (26.7%) patients with cervical cancer (P = 0.0071, 2 test, patient vs control). On the other hand, expression of EGFR was observed in 98% of tumor tissues by immunohistochemistry. CK-19 mRNA and CK-20 mRNA were found in 35 of 45 (77.8%) and 0 of 45 (0%) patients, respectively (NS, chi(2) test, patient vs control). The rate of detection of EGFR mRNA in peripheral blood correlated with FIGO stage (P = 0.049). CONCLUSION: Both CK-19 mRNA and CK-20 mRNA showed no diagnostic value as markers of circulating tumor cells in cervical cancers. However, EGFR mRNA in blood might be a useful marker of circulating tumor cells in cervical cancers.

Profile of neurokinin B concentrations in maternal and cord blood in normal pregnancy.

OBJECTIVE: Neurokinin B (NKB) is a neuropeptide with a vasopressor effect belonging to the tachykinin family. This neuropeptide has attracted attention since recent reports indicated that it is also secreted in the placenta and is probably a cause of pre-eclampsia. To provide a basis for elucidation of the relationship between pre-eclampsia and NKB, this study aimed to clarify the trend of changes in blood NKB levels during normal pregnancy by measuring NKB concentrations in maternal blood during various gestational periods and in umbilical blood. METHODS: Fifty-nine normal pregnant women, 12 normal puerperal women and 24 nonpregnant women were studied. The normal pregnant women comprised of 24 at 8-20 weeks' gestation (early), 11 at 28-34 weeks (middle) and 24 at 35-40 weeks (late). Plasma was separated from peripheral blood samples, umbilical venous blood samples (n = 24) and umbilical arterial blood samples (n = 9). Peptide fractions were extracted from each plasma sample and NKB concentrations were measured by the radioimmunoassay method. RESULTS: The NKB concentration in early pregnancy was not significantly different from that in the nonpregnant state. During pregnancy, the blood NKB concentration increased with advance in gestational week, and a correlation was demonstrated by a linear regression equation. The concentration during puerperium was significantly lower than that in late pregnancy. The umbilical blood concentration was significantly higher than the maternal blood concentration in late pregnancy. There was no significant difference between umbilical venous and arterial blood. CONCLUSION: This study demonstrated that NKB secreted from the placenta during pregnancy enters both the maternal and fetal circulation. These results suggest that NKB may modulate fetoplacental haemodynamics through a paracrine mechanism.

Significance of perivascular lymphocytic infiltrates on survival of patients with invasive cervical cancer.

The authors retrospectively reviewed the medical records of 129 patients with stage IB and II cervical cancer (93 squamous cell carcinomas, 30 adenocarcinomas, and 6 adenosquamous carcinomas) who underwent primary surgery between 1989 and 2000. Vascular invasion is the predictor of recurrence, and lymphocytic infiltrates within the tumor is associated with favorable outcome in cervical cancer. Hence, 129 patients were divided into three groups according to the presence or absence of vascular invasion (VI) and perivascular lymphocytic infiltrates (PLI); VI- (n = 77), VI+PLI- (n = 26), and VI+PLI+ (n = 26), to evaluate the significance of PLI. Age, clinical stage, histology, tumor grade, depth of stromal invasion, VI and PLI, tumor size, ovarian metastasis, pelvic lymph node metastasis, postoperative irradiation, and chemotherapy were assessed statistically for recurrence of the disease by Cox regression analysis. Disease-free survival was analyzed using Kaplan-Meier survival analysis. Recurrence was observed in 32 (25%) of all 129 cases. In a multivariate analysis, VI ( = 0.003) and histology ( = 0.006) remained significantly associated with recurrence. When divided into three groups, the hazard ratio for recurrence was higher in the absence of PLI (2.95 in VI+PLI- group versus 2.07 in VI+PLI+ group), and value became significant in the absence of PLI (0.008 in VI+PLI- group versus 0.106 in VI+PLI+ group). In Kaplan-Meier survival analysis, only the VI+PLI- group ( = 0.006) was significantly associated with worse survival compared with the VI- group. These results suggest that the coexistence of perivascular lymphocytic infiltrates is associated with a better prognosis in cases with vascular invasion.

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor.

OBJECTIVE: This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). METHODS: A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study. RESULTS: The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) (P = 0.028). CONCLUSION: Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.

A case-control study of endometrial cancer after antipsychotics exposure in premenopausal women.

OBJECTIVE: Most endometrial cancers are related to hormonal imbalance, and antipsychotics are a common cause of hyperprolactinemia. We investigated the possible relation between the use of antipsychotics and the risk of endometrial cancer. METHODS: A case-control study was conducted on premenopausal women at the Chiba University Hospital between 1989 and 2000. The cases were 41 patients with histologically confirmed endometrial cancer. For each case, there were 3 controls matched by age and date of visit. Subsequently 123 women without endometrial cancer were enrolled as controls. Detailed information including obesity, parity, hypertension, diabetes mellitus, use of exogenous estrogen and use of antipsychotics was analyzed. Odds ratios, two-sided p values and 95% confidence intervals were estimated by a conditional logistic regression analysis. Radioimmunoassays of serum luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol and progesterone were performed in 4 of 5 patients with endometrial cancer who were using antipsychotics. RESULTS: Use of antipsychotics, diabetes mellitus and obesity were identified as independent variables with risk estimates of 5.4, 9.3 and 4.9, respectively. Serum progesterone, estradiol and prolactin levels ranged from 0.4 to 0.7 ng/ml, 32 to 110 pg/ml and 34 to 258 ng/ml, respectively. CONCLUSIONS: Use of antipsychotics is a risk factor for endometrial cancer, and hyperprolactinemia associated with antipsychotics may impart the risk of endometrial cancer in premenopausal women.

Changes in the incidence of molar pregnancies. A population-based study in Chiba Prefecture and Japan between 1974 and 2000.

BACKGROUND: The aim of this population-based retrospective study was to evaluate the trend in the incidence of molar pregnancy. METHODS: Questionnaires about the occurrence of hydatidiform mole were mailed to all clinics and hospitals in Chiba Prefecture between 1974 and 2000. The diagnosis of hydatidiform mole was based on the post-operative morphological and/or pathological findings. Data of live births were collected from the annual reports of maternal and child health statistics. A total of 3778 women with hydatidiform mole and 1 661 579 women with live births were analysed. RESULTS: The incidence of hydatidiform mole per 1000 live births was constant from 1974 to 1990, while it decreased significantly after 1991 (chi(2)-test for trend, P < 0.0001). The incidence of complete mole also decreased after 1991 (chi(2)-test for trend, P = 0.0001), though the incidence of partial mole remained unchanged. CONCLUSIONS: The incidence of hydatidiform mole in Chiba Prefecture has become as low as that in Europe or the USA, and it is attributed to the decreasing incidence of complete mole. A number of environmental factors that prevent the ovulation of 'empty' oocytes might have contributed to the decreasing incidence of complete mole.