Urinary iodine concentration during pregnancy in an area of unstable dietary iodine intake in Switzerland.

We prospectively investigated urinary iodine concentration (UIC) in pregnant women and in female, non-pregnant controls in the canton of Berne, Switzerland, in 1992. Mean UIC of pregnant women [205 +/- 151 microg iodine/g creatinine (microg l/g Cr); no. = 153] steadily decreased from the first (236 +/- 180 microg l/g Cr; no. = 31) to the third trimester (183 +/- 111 microg l/g Cr, p < 0.0001; no. = 66) and differed significantly from that of the control group (91 +/- 37 microg l/g Cr, p < 0.0001; no. = 119). UIC increased 2.6-fold from levels indicating mild iodine deficiency in controls to the first trimester, demonstrating that high UIC during early gestation does not necessarily reflect a sufficient iodine supply to the overall population. Pregnancy is accompanied by important alterations in the regulation of thyroid function and iodine metabolism. Increased renal iodine clearance during pregnancy may explain increased UIC during early gestation, whereas increased thyroidal iodine clearance as well as the iodine shift from the maternal circulation to the growing fetal-placental unit, which both tend to lower the circulating serum levels of inorganic iodide, probably are the causes of the continuous decrease of UIC over the course of pregnancy. Mean UIC in our control group, as well as in one parallel and several consecutive investigations in the same region in the 1990s, was found to be below the actually recommended threshold, indicating a new tendency towards mild to moderate iodine deficiency. As salt is the main source of dietary iodine in Switzerland, its iodine concentration was therefore increased nationwide in 1998 for the fourth time, following increases in 1922, 1965 and 1980.

Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal women.

OBJECTIVE: To compare the effects of tibolone and conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life (QoL) and tolerability. DESIGN: A double-blind, randomised comparative trial. SETTING: Thirty-seven centres in six European countries. POPULATION: Five hundred and one postmenopausal women, under 65 years of age with an intact uterus. INTERVENTIONS: For 12 months, women received daily treatment with tibolone 2.5 mg (n = 250), or conjugated equine oestrogens 0.625 mg continuously combined with medroxyprogesterone acetate 5 mg (CEE-MPA, n = 251). MAIN OUTCOME MEASURES: The primary outcome was vaginal bleeding rate during cycles 4-6. The secondary outcomes were vaginal bleeding rate during cycles 1-3, 7-9 and 10-13, cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital complaints and tolerability. RESULTS: Treatment with tibolone led to a significantly lower bleeding rate during cycles 4-6 compared with CEE-MPA (15.0% vs 26.9%; P = 0.004); there was a similar difference during cycles 1-3. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital complaints. By intent-to-treat analysis, tibolone significantly improved sexual drive, interest and/or performance, compared with CEE-MPA at 12 months (P = 0.017). Although both treatments were well tolerated, there was a significantly lower incidence of breast tenderness with tibolone than CEE-MPA (2.4% vs 17.1%; P < 0.001). CONCLUSION: The vaginal bleeding rate during cycles 4-6 was significantly lower in women using tibolone. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was significantly less frequent with tibolone.

Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect.

OBJECTIVE: This study sought to confirm the efficacy and safety of the currently recognized dose of Cimicifugae racemosae rhizoma (40 mg/day) and to evaluate a higher dose and its associated physiological effects. METHODS: We conducted a controlled, randomized, double-blinded parallel group study of perimenopausal and postmenopausal women treated with two different doses (39 mg and 127.3 mg) of a unique C. racemosa preparation over a 24-week period. Efficacy and tolerability were determined by the Kupperman Menopause Index, Self-Rating Depression Scale (SDS), a global assessment of tolerability, adverse events, routine hematology, and biochemical tests. To determine if the unique C. racemosa preparation exerts its effect through an estrogen-identical mode of action, we investigated vaginal cytology and gynecologically relevant hormones. RESULTS: Both perimenopausal and postmenopausal patients tolerated the treatment well, and menopausal symptoms decreased regardless of dose (responder rate 70% and 72%, respectively). The lack of change in vaginal cytology measures indicates a nonestrogenic effect of the tested extract in this critical organ. Likewise, the lack of significant changes in the levels of gynecologically relevant hormones does not indicate an overall estrogenic effect. CONCLUSIONS: The higher dose did not exert a significantly greater effect on any end point. Thus, the currently recognized standard dose of the isopropanolic aqueous C. racemosa extract should be preferred over the higher dose. Despite the absence of a placebo group, this study suggests that C. racemosa extract is associated with improvement in menopause symptoms without evidence of estrogenlike effects.

Capacity for hormone production of cultured trophoblast cells obtained from placentae at term and in early pregnancy.

PROBLEM: There is an increased doubt about the identity of isolated cytotrophoblast cells at term. Therefore, we compared pregnancy serum levels of three hormones [human placental lactogen (hPL), human chorionic gonadotropin (hCG), and leptin] with the capacity for hormone production of early placentae [EP; 8-13 weeks of gestation (WG)] and term placentae (TP; 38-42 WG). METHODS: Serum levels of these hormones were determined in 15 paired maternal (7-41 WG) and fetal (37-41 WG) samples. Cytotrophoblast cells were isolated from term (TP; 38-42 weeks) and early (EP; 8-13 weeks) placentae by enzymatic digestion and subsequent purification on a Percoll gradient. These cells were cultured for 6 days. The production of the hormones hPL, hCG, and leptin was determined as release during culture + cell content after culture - cell content before culture. RESULTS: Serum levels (mean +/- SD; n = 15) at 7-12 and 37-41 WG were 89,652 +/- 21,431 and 13,620 +/- 5854 mIU/ml for hCG, 400 +/- 182 and 7088 +/- 2030 ng/ml for hPL, and 12,675 +/- 4266 and 32,236 +/- 10,961 pg/ml for leptin, respectively. For cultured cells from EP and TP, hCG and hPL showed different patterns of release during the first 2-3 days. While the release of these two hormones by EP cytotrophoblast cells continued during 6 days in culture, their concentrations reached a plateau for TP cytotrophoblasts between 4 and 6 days. Leptin was undetectable (< 15 pg/ml) in TP cell cultured media, while for EP all three hormones showed the same release profiles. Production calculated for 30,000 TP trophoblast cells cultured for 6 days (n = 8) was 2-31 mIU for hCG and 0.5-2 ng for hPL. For EP (n = 11), it was 50-1070 mIU for hCG, 15-323 ng for hPL, and 137-580 pg for leptin. Net synthesis of hCG and hPL for TP was > 10-fold and < 1-fold, respectively. In contrast, the production of all three hormones for EP was at least 100 times the initial cell content. CONCLUSIONS: These results demonstrate that trophoblasts from early pregnancy show much higher production rates of hCG, hPL, and leptin than at term. However, the in vitro findings are difficult to be reconciled with the different serum concentrations of the two hormones hPL and leptin observed during the course of pregnancy.

Clear cell adenocarcinoma of the cervix associated with a rare genitourinary malformation.

BACKGROUND: Cervical adenocarcinoma and genitourinary malformations are relatively common disorders, yet their coexistence is rare. CASE: A 49-year-old woman developed clear cell adenocarcinoma in the atretic hemicervix of a communicating uterus type 7 and had ipsilateral renal agenesis. Compared with the unaffected right hemicervix, only the tumor-involved glands of the atretic left hemicervix contained ciliated tuboendometrial cells. Four and a half years after radical hysterectomy and pelvic radiation, she showed no evidence of recurrence. CONCLUSION: In contrast to current opinion, communicating uteri type 7 are associated with ipsilateral renal agenesis. Our histologic findings support the hypothesis that tuboendometrial cells are the cells of origin for cervical clear-cell adenocarcinoma.

Ovarian cancer. an institutional review of patterns of care, health insurance and prognosis.

The purpose of this study was to investigate the prognostic importance of the health insurance status in 145 consecutive patients with ovarian cancer diagnosed between 1984 and 1996. All patients had basic (Type III) insurance to cover outpatient treatment and hospital expenses for a per diem flat fee; some patients had one of two types of supplemental private insurance (Type I and Type II) to cover the treatment by physicians of their choice and fee-for-service hospital treatment. The prognostic impact of health insurance was evaluated by multivariate statistical methods. The median follow-up was 81.9 months (range: 21-181); the 5-year probability of survival was 72% (standard error of the mean (SEM) 9.8%) for stage I, 53% (SEM 16.2%) for stage II, 17% (SEM 5. 9%) for stage III and 11% (SEM 5.5%) for stage IV cancer. Age, stage, histological grade and debulking surgery were independent predictors of survival in multivariate proportional hazards regression analysis. Patients with private insurance were younger and received more chemotherapy than patients with basic insurance. In multivariate analysis, insurance was an independent predictor of survival: patients with Type II insurance had a hazard ratio of 2.31 (95% confidence interval (CI): 1.05-5.04), and patients with Type III insurance had a hazard ratio of 3.30 (95% CI 1.52-7.17) compared with the reference group of Type I insured patients. Health insurance status was an independent predictor of survival in ovarian cancer. Research is needed to devise strategies to improve the medical care of patients with basic insurance.

Production of protein hormones by cultured trophoblast cells isolated from term and early placentae.

PROBLEM: To compare the capacity of de novo hormone synthesis by cultured trophoblast cells isolated from early and term placenta as cytotrophoblast, and to determine the ability of these cells to proliferate in culture. METHOD OF STUDY: Cytotrophoblast cells were isolated from term (TP, 38-42 weeks) and early placentae (EP, 8-13 weeks) by enzymatic digestion and subsequent purification on a percoll gradient. The net synthesis of the hormones human placental lactogen (hPL) and human chorionic gonadotropin (hCG) was determined as the release during culture + cell content after culture - cell content before culture. Proliferation was determined using a dedicated colorimetric reagent (CellTiter 96). RESULTS: Using a percoll gradient we were able to isolate three cell bands with densities of 1.051, 1.058, and 1.063 g/mL, which were predominantly cytotrophoblast cells as shown by immunocytochemical analysis. The cytotrophoblast cells with the highest density (1.063 g/mL) were used because they were found to release the highest amount of hormones and have shown the lowest rate of cell death after 6 days in culture. Both hCG and hPL showed different patterns of release during the first 2-3 days of culture between TP and EP. While the release by EP cytotrophoblast cells continued during 6 days of culture (n = 4), the concentrations for TP cytotrophoblast (n = 4) reached a plateau between 4 and 6 days. Net de novo synthesis calculated for 3 x 10(4) TP trophoblast cells cultured for 6 days (mean +/- SD, n = 4) was 8.65 +/- 9.05 mU for hCG and 0.95 +/- 0.45 ng for hPL. For EP, it was 395.5 +/- 265.5 mU for hCG and 148.8 +/- 84.2 ng for hPL. Net synthesis of hCG was > 10-fold (TP) and > 70-fold (EP) higher than the initial cell content. While at term, hPL synthesis was only a fraction of the initial cell content, production by EP cytotrophoblast was 106 times the initial cell content. The extent of cell death after 6 days in culture was significantly (P < 0.02) higher for term (30-40%) than for early trophoblast (10-20%). Using a proliferation detection agent during the first 3 days of culture with first trimester cytotrophoblast cells, we did not find any changes in the proliferative activity. CONCLUSIONS: There are differences in the functional activity between trophoblast cells obtained from first and third trimester. The in vitro findings are difficult to reconcile with the different patterns of plasma concentrations of the two hormones observed in vitro during the course of pregnancy.

Three-dimensional laparoscopy. Gadget or progress? A randomized trial on the efficacy of three-dimensional laparoscopy.

BACKGROUND: This study was designed to compare conventional laparoscopy with three-dimensional (3-D) laparoscopy. METHOD: Thirty candidates, 20 inexperienced and 10 experienced in operative laparoscopy, executed standardized exercises on a pelvitrainer. The candidates were randomized to two groups. Group A executed the exercises first with the conventional and then with the three-dimensional system. Group B accomplished the exercises in the reverse sequence. At the end of the exercises, the candidates answered specific questions about the two systems. RESULTS: A total of 21 h 6 min 6 sec of laparoscopic exercises were analyzed-10 h 8 min 1 sec with the conventional and 10 h 58 min 5 sec with the three-dimensional system (p = 0.38). Group A required 12 h 26 min 56 sec to perform all the exercises. There was no statistically significant difference from group B, where the candidates needed 8 h 39 min 10 sec (p = 0.14). Neither were there any differences in the number of failed attempts between the two groups. There were also no statistical difference when the results obtained from the candidates without experience in laparoscopy and the participants experienced in operative laparoscopy were analyzed separately. Both the inexperienced and the experienced candidates became tired earlier, had more headaches, and needed extra time to adapt to the 3-D system. CONCLUSION: When analyzed in a standardized fashion, 3-D laparoscopy does not have any significant advantages over conventional laparoscopy.

Lymphadenectomy in high risk endometrial carcinoma stage I and II: no more morbidity and no need for external pelvic radiation.

The objectives of this retrospective study were to analyze the morbidity of surgical staging and to evaluate the omission of external radiotherapy in high-risk patients with stage I and II endometrial carcinoma when the lymph nodes were negative. From 1988 to 1996, 63 of 117 patients underwent a pelvic and periaortic lymphadenectomy. The decision to perform lymphadenectomy was influenced by patient general health. Patients with lymphadenectomy had a better physical status (P < 0.0001). Lymphadenectomy increased mean operative time (P < 0.0001) and blood loss (P < 0.01), but there was no increase in postoperative complications. At a median follow-up of 54 months, there was one cuff recurrence in 56 patients. Nineteen high-risk patients without external pelvic radiation had the same disease-free survival rate as 37 low-risk patients (P = 0.1). In the group without lymphadenectomy, the disease-free survival for 18 high-risk patients and 32 low-risk patients was similar (P = 0.21). Surgical staging in properly selected patients does not increase postoperative complications and brachytherapy without external radiotherapy is associated with excellent disease-free survival when the lymph nodes are negative.

[Sentinel lymphadenectomy: an alternative to axillary lymphadenectomy in breast carcinoma]. / Sentinel-Lymphadenektomie: eine Alternative zur axillären Lymphadenektomie beim Mammakarzinom.

BACKGROUND: Axillary lymph node status is an important determinant of prognosis in breast cancer. However, lymphadenectomy does not benefit half of the patients in whom axillary nodes are free of disease. Sentinel lymph node biopsy is a new technique which allows accurate staging of breast carcinoma without performing total axillary dissection. We describe our experience with the introduction of sentinel lymphadenectomy. METHODS: Thirty-seven sentinel lymphadenectomies were performed in 35 patients referred to the Department of Obstetrics and Gynaecology of the University of Berne between December 1997 and June 1998. Mapping procedures were performed using a combination of vital blue dye with preoperative lymphscintigraphy with 99mTechnetium-labelled colloidal albumin and intraoperative use of a gamma probe. Complete axillary lymphadenectomy was then performed in 34 patients. RESULTS: One or more lymph nodes were identified in 33 of 37 procedures (89%). With the combination of both localisation techniques the sentinel nodes were identified in all (100%) of the last 19 patients. Sentinel and non-sentinel lymph nodes were always concordant. In this series the negative predictive value is 100% (95% confidence interval: 87.7%-100%). Metastases were found in the sentinel node in 11 of 30 patients (37%). From these 11 patients, 3 (27%) had micrometastases. CONCLUSIONS: Histopathologic examination of the sentinel lymph node accurately predicts the axillary lymph-node status. Patients with sentinel nodes free of metastases could avoid the unnecessary peri- and postoperative complications of complete axillary dissection. Further studies are needed to assess whether the improved diagnosis of micrometastases by sentinel lymphadenectomy influences the long-term prognosis of breast cancer.

Is laparoscopic oophorectomy rational in patients with breast cancer?

BACKGROUND: Unsuspected malignancy remains a problem for the laparoscopic surgeon. The aim of this study was to evaluate the risk of ovarian micrometastasis in patients with breast cancer who undergo laparoscopic oophorectomy. METHODS: We analyzed 25 premenopausal women with breast cancer who underwent therapeutic laparoscopic oophorectomy. The patients were subdivided into the following two groups according to ovarian pathology: group A with and group B without breast carcinoma micrometastasis. We then reviewed the follow-up data for both groups, with special attention to metastasis of the abdominal wall. RESULTS: Twelve of 44 ovaries removed by laparoscopy showed ovarian breast carcinoma micrometastasis. There were no predictive factors of micrometastasis. After a mean follow-up of 38.1 months (95% CI: 29.2-46.9 months), none of the patients with proven micrometastasis developed metastasis of the abdominal wall, and the 21 puncture sites were inconspicuous. CONCLUSIONS: Although 32% of patients may have unexpected ovarian micrometastasis, laparoscopic oophorectomy in patients with breast cancer remains a safe procedure.

Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women.

OBJECTIVE: To compare the effects on body composition and body weight of tibolone vs two different sequential oral or transdermal oestrogen-progestogen hormone replacement therapies versus no therapy. PATIENTS AND METHODS: One hundred postmenopausal women were assigned to a control group (n = 26), or randomized to 1) tibolone (TIB) 2.5 mg/day (n = 28), 2) oral oestradiol 2 mg/day (PO) plus sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 26), or 3) transdermal oestradiol patch (TTS) releasing 50 micrograms/day plus oral sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 20). Body composition was measured at the base-line and every 6 months for 2 years by DXA (Hologic QDR 1000 W). RESULTS: Total body fat mass increased (P < 0.05) in controls (+3.6 +/- 1.5%) and in TTS treated (+4.7 +/- 2.2%), but not in PO (-1.2 +/- 2.4%) and TIB (-1.6 +/- 2.2%) treated subjects. This increase in total fat mass in controls and TTS treated women was mostly due to an increase in fat mass of the trunk (P < 0.05), but not legs. As a result, a redistribution of body fat to the trunk occurred in controls, TTS and TIB, but not in PO treated women (P < 0.05). Total lean body mass decreased (P < 0.02) in controls (-1.7 +/- 0.7%) and PO (-1.4 +/- 0.6%) but not in TTS (+0.3 +/- 0.8%) and TIB (+0.4 +/- 0.5%) treated subjects. CONCLUSIONS: The menopause is associated with an increase in total body fat and a decline in lean body mass. Oral oestradiol/dydrogesterone and tibolone prevent total body fat changes, whereas transdermal oestradiol/oral dydrogesterone and tibolone prevent the lean mass changes. Furthermore, oral oestradiol/dydrogesterone prevents the shift to a central, android fat distribution.

[Urogenital complaints: value of systemic estrogen therapy]. / Urogenitale Beschwerden: Platz der systemischen Ostrogen-Therapie.

Local and systemic therapies with estrogens lead to a fast alleviation of urogenital symptoms, which occur frequently in the postmenopausal women. Especially atrophical changes in vulva and vagina, but also complaints about incontinence are improved by estrogen therapy. Even though there is no objective evidence of an improvement of stress incontinence, there are less infections of the lower urinary tract as well as a diminution of urge incontinence. Moreover, systemic estrogen therapy helps to prevent postmenopausal osteoporosis and cardiovascular diseases. Urogenital complaints may motivate patients easily for a long lasting systemic estrogen therapy, because symptoms are bothering and annoying.

Pelvimetry by magnetic resonance imaging as a diagnostic tool to evaluate dystocia.

OBJECTIVE: To test the clinical value of magnetic resonance imaging (MRI) pelvimetry for the diagnosis of cephalopelvic disproportion. METHODS: All deliveries from January 1993 through December 1994 were reviewed to identify 42 nulliparas at term with vertex presentation and cesarean delivery due to dystocia. Complete data were available for 41 women, and subjects were divided into the following two subgroups, according to clinical data: "cephalopelvic disproportion" (n = 28) and "failure to progress" (n = 13). Ten nulliparous women with uncomplicated vaginal delivery served as controls. Pelvimetry data from postpartum MRI were correlated with fetal and neonatal dimensions to evaluate various criteria for the diagnosis of cephalopelvic disproportion. RESULTS: Comparing both the fetal head volume derived from antepartum ultrasound assessment and the neonatal head volume (postpartum measurement) with maternal pelvic capacity determined by MRI, cephalopelvic disproportion (head volume exceeding pelvic capacity) indicated that 25 and 27, respectively, of the 28 women had been clinically diagnosed correctly with cephalopelvic disproportion, corresponding to sensitivities of 89% and 96%, respectively. Fetal head volume was not larger than pelvic capacity in any of the women in the control group. In seven of the 13 women diagnosed as "failure to progress," the fetal head volume exceeded the pelvic capacity. CONCLUSION: A fetal head volume estimate exceeding MRI-measured pelvic capacity is a frequent finding in nulliparas with cesarean birth due to cephalopelvic disproportion. An appropriate prospective study to determine the benefits of an antepartum diagnosis of cephalopelvic disproportion in high-risk nulliparas is warranted.

Long-term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study.

OBJECTIVE: To assess the influence of three different postmenopausal hormone replacement therapies on levels of serum lipids and lipoprotein(a) [Lp(a)]. DESIGN: Open, randomised, controlled study. PARTICIPANTS: One hundred and forty healthy, early postmenopausal women. INTERVENTIONS: The women were randomised to receive continuous 17 beta-oestradiol, either orally (2 mg daily; n = 35) or transdermally (50 micrograms daily; n = 35), plus 10 mg dydrogesterone daily for 14 days of each 28-day cycle; or 2.5 mg tibolone daily (n = 35). Thirty-five untreated women acted as controls. MAIN OUTCOME MEASURES: Fasting blood samples were analysed at baseline, 6, 12 and 24 months for low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, very low density lipoprotein (VLDL), total cholesterol, triglycerides, lipoprotein(a)[Lp(a)], apolipoproteins A-1, A-2 and B, fibrinogen, and antithrombin factor III. RESULTS: At 24 months oral oestradiol increased mean HDL cholesterol (7%; 95% CI 1-14), compared with no change in the transdermal group and a decrease of 26.8% in the tibolone group (95% CI 22.9-30.5); oral oestradiol decreased mean LDL cholesterol (11.8%; 95% CI 6.3-19), compared with no change in the tibolone group. Changes in apolipoprotein A-1 and B showed a similar pattern to HDL and LDL cholesterol, respectively. Oral oestradiol increased serum triglycerides (30%; 95% CI 18-42) after 24 months, compared with no change in the tibolone and transdermal oestradiol groups. Tibolone decreased serum Lp(a) by 36.6% after 24 months (95% CI 8.3-56.2), oral oestradiol decreased levels by 29.4% (95% CI 2-51.1), compared with no change in the transdermal oestradiol group. CONCLUSIONS: Oral and to a lesser extent transdermal oestradiol when sequentially combined with dydrogesterone, showed a beneficial influence on serum lipids regarding the cardiovascular disease risk, which was not seen with tibolone. The significance of Lp(a) levels on cardiovascular disease risk remains to be determined.

Comparison of transvaginal ultrasonography and endometrial biopsy in endometrial surveillance in postmenopausal HRT users.

OBJECTIVES: To compare transvaginal ultrasonography with histological findings in endometrial evaluation of postmenopausal women using hormone replacement therapy and to evaluate endometrial safety of three hormone replacement therapy regimens. METHODS: In a randomized, comparative study in postmenopausal women, endometrial safety was evaluated using (1) no hormone replacement therapy, (2) oral micronized 17 beta-estradiol/oral sequential dydrogesterone, (3) transdermal 17 beta-estradiol/oral sequential dydrogesterone, or (4) oral tibolone. 85 Non-hysterectomised subjects underwent transvaginal ultrasonography immediately before Pipelle biopsy at baseline and subsequently after 12 and 24 months. Endometrial thickness and uterine dimensions were determined by transvaginal ultrasonography, and endometrial thickness (double-layer) was compared with biopsy results. RESULTS: Endometrial evaluation was conveniently performed by transvaginal ultrasonography, and endometrial thickness correlated well with biopsy findings. If endometrial thickness was < 5 mm, the endometrial biopsy sample was either inactive/atrophic or insufficient for histopathological diagnosis. Hyperplastic or malignant changes were not reported. After 24 months, endometrial thickness was increased both in the oral (P < 0.001) and transdermal (P < 0.001) 17 beta-estradiol/dydrogesterone groups, whereas with tibolone the change in endometrial thickness was not different from controls. CONCLUSION: transvaginal ultrasonography of the endometrium reliably predicts the histological picture in hormone replacement therapy users. Using 5 mm endometrial thickness as cut-off point, more than 75% of biopsies could be avoided. All three hormone replacement therapies were safe with respect to the endometrium. With sequential 17 beta-estradiol/dydrogesterone the expected progestogen-induced secretory pattern was observed, whereas endometrial histology under tibolone closely mimicked the natural atrophic postmenopausal state.

[Etiology and perinatal medical significance of prematurity below 1,500 g]. / Ursachen und perinatal-medizinische Bedeutung der Frühgeburten unter 1500 g.

305 preterm babies with birthweight below 1500 g were delivered at our centre between 1991 and 1994. Classification according to etiology shows that more than half (52.7%) of these deliveries had to be induced secondary to underlying fetal or maternal pathology. A more efficient tocolysis could have prevented up to one third of these deliveries (31.4%). The main cause of each preterm delivery was defined according to Whitfield's etiological classification. In decreasing order of frequency we found hypertensive disorders of pregnancy, multiple pregnancy, preterm premature rupture of membranes, preterm labour and vaginal bleeding in the third trimester. The majority of these deliveries (88.6%) were prenatal referrals, reflecting widespread regionalization of obstetric services in Switzerland. Nevertheless, 64 women (24.2%) with threatening preterm labour before the 32nd week of gestation had to be denied admission to our hospital because of shortage of neonatal intensive care beds, or had to be transferred from our hospital to another offering perinatal facilities during the study period (1991-1994). Acute lack of neonatal intensive care unit beds in Switzerland requires closer attention in the future.

[Secondary prevention in coronary diseases. Viewpoint of the gynecological endocrinologist]. / Sekundärprophylaxe bei Koronarerkrankungen. Sicht des gynäkologischen Endokrinologen.

Although reduction of cardiovascular risk by estrogen substitution in the menopause has not been proven by a prospective randomized study the results of the present epidemiologic studies with the most various methodological approaches leave hardly any doubt about such a protective effect. Furthermore the published data show that women with cardiovascular risk factors or with a preexisting cardiovascular disease benefit more from estrogen substitution than healthy women. Addition of gestagen in non hysterectomized women for the reduction of increased risk for endometrial cancer seems to impair the benefit for cardiovascular risk only minimally if at all.

[Diagnosis and biopsy of nonpalpable breast lesions]. / Diagnostik und Biopsie nicht-palpabler Mammaläsionen.

In a retrospective analysis we reviewed 117 needle-localized biopsies of nonpalpable breast lesions in 115 women from the senologic outpatient clinic at the Women's Hospital of the University of Berne. In a logistic regression analysis, the age of the patient, the presence of grouped and irregular microcalcifications as well as the presence of a stellate lesion in mammography correlated closely with the diagnosis of breast cancer. The prevalence of malignant lesions, which was equal to the rate of preoperative correctly diagnosed malignancy in this group, was 22.2%.