IGFBP-1 and glycodelin serum levels before and after hysterectomy with and without bilateral oophorectomy in premenopausal women.

OBJECTIVES: The aim of our study was to investigate the role of the intact endometrium and ovaries for serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) and glycodelin. STUDY DESIGN: In 35 premenopausal patients with a planned hysterectomy, serum measurements of IGFBP-1 and glycodelin were done before surgery and 1, 3, 5, and 10 days after surgery. Patients were divided into three groups according to the kind and time of operation: (1) hysterectomy with bilateral adnexectomy in the luteal phase and (2) hysterectomy without adnexectomy in the follicular phase or (3) the luteal phase. RESULTS: IGFBP-1-we could not show any differences in IGFBP-1 serum levels before and after hysterectomy with or without bilateral oophorectomy. Glycodelin-hysterectomized and oophorectomized patients showed decreasing serum levels up to day 3. After day 5, circulating concentrations of glycodelin increased continuously but remained below pre-operative levels. In both non-adnexectomized groups we saw a reduction up to day 5 but a rise at day 10. None of the results reached statistical significance. CONCLUSION: The results indicate that endometrium and ovary are not the only sources of IGFBP-1 and glycodelin.

Results of a prospective comparative study of transvaginal hydrolaparoscopy and chromolaparoscopy in the diagnostics of infertility.

Transvaginal hydrolaparoscopy (THL) was evaluated in comparison with the already established chromolaparoscopy in the detection of tubal factors, adhesions as well as endometriosis. 43 infertile patients without previous pelvic operations and with an inconspicuous clinical examination were included in a prospective comparative study of THL and chromolaparoscopy. THL succeeded in 40 patients (93.0%). Both methods showed 100% agreement with regard to tubal factors and adhesions. However, only 72/80 tubes (90.0%) could be portrayed by THL. In contrast to this, THL failed to identify 8 of 10 laparoscopically verified endometrioses (isolated endometriosis of the bladder peritoneum in 2). No complications occurred with THL. THL could be the method of choice for the clarification of mechanical infertility factors in symptom-free patients with no suspicion of pelvic pathologies. Tubal pathologies and/or adhesions (visible during THL) should be indications for laparoscopy. In the case of inconspicuous genitals during THL and a still unfulfilled desire for offspring postoperatively, laparoscopy should be considered in order to exclude the possibility of unidentified endometriosis. Retroflexio uteri should at least be a relative contraindication for THL. Further studies are necessary to evaluate the role of THL in the diagnostic concept of infertility in the future.

Conservative treatment of ectopic pregnancy in a cesarean section scar with methotrexate: a case report.

Ectopic pregnancies sited in dehiscent cesarean section scars have a high risk of rupture and bleeding. Attempts at operative therapy frequently end in loss of the uterus. A connection with the cavum uteri justifies an attempt at dilatation and curettage. We describes a patient with combined systemic and local intra-amniotic methotrexate (MTX). The uterus was preserved.

Menorrhagia and adenomyosis in a patient with hyperhomocysteinemia, recurrent pelvic vein thromboses and extensive uterine collateral circulation treatment by supracervical hysterectomy.

A 37-year-old patient had recurring thromboses, occlusion of the left femoral vein with hereditary hyperhomocysteinemia, hypermenorrhea and anaemia. Conservative therapy with endometrium ablation and gestagene failed. A supracervical hysterectomy was done to preserve the presacral and left lateral, dorsal and caudal collaterals beside the uterus, and prevent a postoperative congestion, especially of the left leg.

Bilateral ovarian fibromas and endometrial adenocarcinoma in a postmenopausal patient with growing uterine myomas.

Bilateral ovarian fibromas are a rare condition. We report a case of bilateral ovarian fibromas with endometrial adenocarcinoma in a postmenopausal woman who clinically showed symptoms of an estrogen-producing tumour. Clinical and histopathological problems in the pre- and intraoperative diagnostics of fibromas are discussed.

Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy.

OBJECTIVE: To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. STUDY DESIGN: Two prospective open-label studies with longitudinal follow-up in the second trial. SETTING: Academic Department of Obstetrics and Gynecology, University of Cologne. PATIENTS: Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. MAIN OUTCOME MEASURE: Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. RESULTS: Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. CONCLUSION: Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.

[Uterus septus with primary infertility - an operating indication?]. / Uterus septus bei primärer Sterilität - eine Operationsindikation?

OBJECTIVE: The following retrospective study is intended as a contribution towards determining the necessity of a hysteroscopic metroplasty in patients with primary infertility. - MATERIAL AND METHODS: 21 patients with primary infertility and a septate uterus, who had undergone a hysteroscopic dissection of the septum between 1993 and 2000, were evaluated. With the help of medical records, operation reports, standardised questionnaires as well as telephone contact with the patient's doctor and/or the patient, anamneses, operation as well as postoperative development were recorded. - RESULTS: All dissections of the septum occurred without complication. During follow-up (median 24.0 +/- 23.7 months), 11/21 patients became pregnant (52.4 %). Of these 11 pregnancies, 7 ended (63.3 %) at full-term, 2 (18.2 %) prematurely and one (9.1 %) as a miscarriage. One pregnancy is currently in the 3(rd) trimester. - CONCLUSIONS: The hysteroscopic metroplasty demonstrates a low intra- and postoperative rate of complication. Particularly the indication of a lower rate of miscarriages, possibly of an increase in the pregnancy rates, should, in our opinion, give reason to proceeding with a diagnostic hysteroscopy, especially prior to extensive sterility therapies. Where suspicion exists of a septum > 1.0 cm, this should be corrected by means of an operative hysteroscopy.

[The significance of leptin for reproduction]. / Zur Bedeutung von Leptin für die Reproduktion.

Leptin is mainly synthesized by adipocytes and might represent the connecting link between fatty tissue and brain. In reference to reproduction, leptin resistance could play a role particularly in the pathogenesis of the PCO syndrome. However, there exists at present contradictory data on this, so that further clarification is necessary. Leptin interacts with the steroid synthesis to a degree not yet precisely clarified and possesses receptors in numerous tissues, which suggests extensive local and endocrine effects. Its exact significance for the initiation of puberty still remains unknown. The same is true for first data regarding leptin and endometriosis and the interpretation of hyperleptinemia during pregnancy. It is clear that this protein mediates between fatty tissue and the reproductive function. However, the detailed physiologic and pathophysiologic role of leptin in reproduction can only be clarified through further extensive studies. To date there is not yet a practical importance for the measurement of leptin in routine work in reproductive medicine.

[Parameters of lipid metabolism in postmenopausal women on oral or transdermal hormone replacement with or without progesterone]. / Lipidstoffwechselparameter postmenopausaler Frauen unter oraler und transdermaler Hormonsubstitution mit oder ohne Gestagenzusatz vom Progesterontyp.

OBJECTIVE: Aim of the study was to show different influences of transdermal and oral hormone replacement therapies (conjugated and micronized estrogens) with or without varying dosages of C21-progestogens on serum lipids and lipoproteins. MATERIAL AND METHODS: We report on serum triglycerides, cholesterol, HDL-, LDL-cholesterol, apolipoprotein A 1 and B levels of 80 postmenopausal women, who received hormone replacement therapies for more than one year. RESULTS: All patients showed increasing (non-significant) serum HDL/LDL-cholesterol-ratios. Transdermal estrogen monotherapy also influenced the lipid parameters in a positive way. Apolipoprotein B, cholesterol and LDL-Cholesterol decreased, apolipoprotein A 1 increased. Transdermal replacement therapy combined with C21-progestagens and all oral therapies resulted in HDL-cholesterol increases. Positive changes in lipid parameters were most remarkably in women receiving oral therapies. The addition of 42 mg medrogestone/cycle caused a more significant decrease of cholesterol serum levels than higher dosages of medrogestone did. During subsequent treatment cycles, serum triglycerides showed increasing levels within the reference limits in women receiving conjugated estrogens and medrogeston. CONCLUSIONS: Transdermal and oral hormone replacement therapies with and without C21-progestogens are ideal for hormone replacement therapy in postmenopausal women with normal or minor pathological lipid parameters. The lowest possible medrogestone dose necessary for endometrium protection should be used.

[Effect of hormone replacement therapy during the climacteric on cerebrovascular diseases]. / Einfluss einer Hormonsubstitution im Klimakterium auf zerebrovaskuläre Erkrankungen.

In epidemiological and animal studies it could be shown that a hormone replacement therapy decreased the risk of stroke. Sonographical blood flow measurement shows a positive effects to the cerebrovascular system caused by estrogen which was not modified by gestagens. In morphometric investigations by sonographical measurements of intima-media-thickness, it could be demonstrated that a positive influence by hormone replacement therapy can be achieved for a longer time. The intima-media-thickness, as a sign of a complex atherosclerosis, is decreased. The number of atherosclerotic plaques is significantly lower in patients receiving hormone replacement therapy (HRT) in comparison to a control group. A regression of the plaques by estrogen replacement therapy could be shown in one study. Although the group of patients suffering from stroke is heterogeneous, the benefit of HRT for prevention of cerebrovascular diseases could clearly be demonstrated. HRT is not contraindicated in patients suffering from cerebrovascular diseases. In most of cases, HRT is recommended in these patients. The therapeutic effect of HRT for cerebrovascular disease should be proved in further prospective studies.

[Maternal CA 125 serum level in intrauterine pregnancy and abortion in the first trimester]. / Mütterliche CA 125-Serumspiegel bei intrauterinen Schwangerschaften und Aborten im ersten Trimenon.

OBJECTIVE: Maternal CA 125 levels are supposed to rise in pregnancies complicated by vaginal bleedings in dependence to the extent of decidual disruption which is directly related to the outcome of pregnancy. MATERIAL AND METHODS: The prognostic value of maternal CA 125 serum measurement was investigated in 239 women with a first trimester intact pregnancy, imminent, incomplete, complete or missed abortion. RESULTS: 43.9% of the CA 125 serum levels were without normal range (> 20 U/ml). Mean CA 125 serum levels were higher in patients with incomplete (52.4 +/- 67.4 U/ml), complete (34.3 +/- 46.1 U/ml), and imminent abortion (33.0 +/- 45.8 U/ml) as compared with normal pregnancies (28.9 +/- 28.8 U/ml) and missed abortion (23.5 +/- 21.5 U/ml). CA 125 levels in first trimester pregnancies tended to be higher in patients with vaginal bleedings than in patients without bleeding (40.5 U/ml +/- 55.0 vs. 28.9 U/ml +/- 28.8; p = 0.65). CONCLUSIONS: For clinical use CA 125 serum measurement is not relevant. First trimester CA 125 measurement can not serve as an accurate predictor of pregnancy outcome due to the wide overlap of ranges.

[Effect of isoflavones on mammary gland and endometrium of postmenopausal macaques (Macaca fascicularis)]. / Die Wirkung von Isoflavonen auf das Mammagewebe und Endometrium postmenopausaler Makaken (Macaca fascicularis).

OBJECTIVE: Because of their beneficial effects on atherosclerosis and cancer risk, isoflavones may be useful as a dietary alternative or supplement to postmenopausal hormone replacement therapy. Isoflavones belong to the most important phytoestrogens. They may have estrogenic and antiestrogenic effects. We examined this in a well-characterised primate model of the postmenopause. MATERIAL AND METHODS: Adult, surgically postmenopausal female macaques were treated with isoflavones, estradiol or placebo for 6 months. After 6 months of therapy histopathological, morphometrical, and immunohistochemical measurements of endometrium and mammary glands were performed. RESULTS: 6 months of isoflavone-therapy did not induce proliferation or any other clinical important changes in endometrium and mammary tissue. Phytoestrogentherapy did not show estradiol comparable effects. We are discussing our results with the results of other studies, which are sometimes in contrast. CONCLUSIONS: Our results indicate that isoflavones do not have estrogenic effects in the tissues studied.

Pre- and postoperative hormonal treatment in patients with hysteroscopic surgery.

Hysteroscopic surgery is widely used for the treatment of patients suffering from infertility and menorrhagia. Preoperative and postoperative treatment plays an important role in this kind of surgery. The indications for hormonal pre- and postoperative treatment are very different and depend on the type of surgery and the condition of the patient. For a septum dissection, preoperative treatment is not necessary. Postoperative estrogen therapy can be helpful especially after dissection of a large septum. For intrauterine adhesiolysis, preoperative treatment is without benefit. In cases of adhesions of grades 3 and 4, postoperative treatment entailing insertion of an IUD and application of estrogens for about 3 months is recommended. A higher amenorrhea rate after endometrium ablation can be reached by pretreatment with a GnRH analogue or danazol. For resection methods, pretreatment is not necessary in any case. The success rate of endometrium ablation (reduction of blood loss) is not influenced by pretreatment. Pretreatment can be useful in coagulation techniques in patients suffering from secondary anemia and in high-risk patient. In patients who need hormone replacement therapy after endometrium ablation, gestagen application is necessary. For prevention of bleedings, a continuous combined hormone replacement therapy should be used and so a bleeding-free treatment is possible. The residual endometrium will so be protected against hyperplasia. Another alternative postoperative method after endometrial ablation is insertion of a levonorgestrel IUS. Our studies show advantages for protection of the endometrium, for contraception and a high amenorrhea rate. Prior to a hysteroscopic myoma resection, pretreatment with GnRH analogues is indicated for all myomas with a diameter of more than 3 cm and/or an intramural portion or for patients suffering from secondary anemia. The aim of the pretreatment is not only to obtain a thin endometrium but also to reduce the size and vascularization of the myomas. The failure rate in patients not treated with GnRH analogues is higher especially in large intramural myomas. Pre- and postoperative hormonal treatment can be effective, especially in the treatment of patients suffering from menorrhagia. The indications for hormonal pre- and postoperative treatment should be very strong. A hysteroscopic surgeon should be also have some experience in hormonal treatment.

Hydrothermal ablation. A new simple method for coagulating endometrium in patients with therapy-resistant recurring hypermenorrhea.

Hydrothermablation is a new method which could replace the electrosurgical method of endometrial ablation. Some prospective studies were carried out to assess efficacy, safety and tolerability of hydrothermablation in the treatment of recurrent menorrhagias. Hydrothermablation is an intervention with coagulation at the endometrium: temperature 90 degrees C and duration 10 min with simultaneous hysteroscopic control. In a follow-up of least 12 months, about 35% of the patients had an amenorrhea and the treatment was successful (reduction of pathological blood flow) in about 87% of the patients. Complications were vaginal burns in 2 cases. No other intra- or postoperative complications occurred. Hydrothermablation is a safe and effective method for treatment of recurrent menorrhagias. This method offers a simple possibility to perform endometrial ablation without extensive training of the surgeon and can contribute to avoid hysterectomy.

Possibilities of sterility therapy in a patient with a premature menopause due to an X-chromosomal anomaly - a case report.

Our report concerns a patient with a climacterium praecox and an X-chromosomal anomaly (86% 46, XX; 7% 47, XXX; 7% 45, X0) desiring to give birth. She conceived once after down-regulation of the gonadotrophins by means of a cyclical hormone replacement therapy followed by gonadotrophin stimulation, as well as a second time under down-regulation with a GnRH-analogue and gonadotrophin stimulation. On the basis of the case report and of the literature, a possible interval therapy in such a patient, especially one even with increasing ovarian insufficiency, will be portrayed and discussed.

[Effect of long-term hormone substitution therapy on serum TSH level in postmenopausal women]. / Einfluss einer Langzeithormonsubstitutionstherapie auf die TSH-Serumspiegel von postmenopausalen Frauen.

OBJECTIVE: Dysfunction's of the thyroid gland are one of the most important endocrinological diseases. We report serum TSH levels in postmenopausal women before and during long-term hormone replacement therapy. MATERIAL AND METHODS: 107 postmenopausal patients participated in this study. Criteria for inclusion were: no known thyroid dysfunction and request for hormone replacement. Before starting therapy TSH serum levels were measured in each patient. If basal levels were within normal range TSH serum levels were reported over 4 years of hormone replacement therapy. RESULTS: More than 10% of the postmenopausal women showed pathological TSH-levels without clinical symptoms requiring further diagnostic. During subsequent treatment cycles (4 years) serum TSH in euthyroid patients did not show significant changes. Women using hormone replacement therapy developed no new manifestation of thyroid disease. CONCLUSION: In euthyroid women using long-term hormone replacement therapy are no changes in thyroid function caused by hormone replacement therapy to expect.

Effects of mammalian and plant estrogens on mammary glands and uteri of macaques.

Because of their possible beneficial effects on atherosclerosis and cancer risk, soy-derived isoflavone phytoestrogens may be useful as a dietary alternative or supplement to postmenopausal hormone replacement therapy. We examined this possibility in a well-characterized primate model of postmenopause. Adult, surgically postmenopausal female macaques (Macaca fascicularis) were treated continuously with either estradiol (E2), an isoflavone-rich soy protein isolate (SPI), or both (E2+SPI). Doses were equivalent on an energy basis to 1 and 148 mg/d per woman for E2 and SPI, respectively. After 6 mo, histopathologic, morphometric, and immunohistochemical measurements of the endometrium and mammary glands were taken. Increases in endometrial thickness, gland area, and epithelial proliferation were induced by E2 and E2+SPI. Morphometric changes were accompanied by increased epithelial staining of the proliferation marker Ki-67 in the E2-treated group. The effects of E2 were partially antagonized by SPI (manifested as decreased Ki-67 staining). Mammary gland proliferation was induced by E2 and E2+SPI. The effects of E2 were also antagonized by SPI in the mammary gland. Morphometric and immunohistochemical measures of proliferation were in agreement in endometrium. In this nonhuman primate model, treatment with SPI did not induce proliferation in endometrial and mammary tissue. SPI may have antiproliferative effects in the endometrium and mammary gland when given along with exogenous estrogen.