Improvement in menopausal symptoms with a nutritional product containing evening primrose oil, hop extract, saffron, tryptophan, vitamins B6, D3, K2, B12, and B9.

OBJECTIVE: Safety concerns or contraindications in the use of hormones have resulted in a rise in the use of nutritional medicinal products for the management of menopausal symptoms. The aim of the present study was to demonstrate the efficacy and safety of Exelvit Menopause®. PATIENTS AND METHODS: A prospective, open, observational, and multicentre study was performed, including 156 menopausal women. The patients received the nutritional product containing evening primrose oil 50 mg; hop extract 0.127-0.212 mg; saffron Stigmas Extract 0.6 mg; tryptophan 71.25 mg, vitamins B6, D3, K2, B12, and B9 once per day for 12 weeks. The validated menopausal rating score (MRS) was used for recording symptoms. RESULTS: A decrease in the MRS of all menopausal symptoms was observed after 12 weeks compared to baseline (p < 0. 0001). Overall, hot flashes were reduced by 48.15%, heart discomfort by 33.3%, sleep disturbance by 46.2%, joint and muscular discomfort by 27.8%, depressive mood by 45.0%, irritability by 47.6%, anxiety by 44.4%, physical problems by 36.4%, sexual problems by 30.0%, bladder problems 31.3%, and vaginal dryness by 33.3%. CONCLUSIONS: The nutritional product Exelvit Menopause® significantly reduced menopausal symptoms.

Bone health in estrogen-free contraception.

Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.

Progesterone in Peri- and Postmenopause: A Review.

Around 14.5 million peri- and postmenopausal women currently live in Germany. Moreover, approximately 450 000 women, each with a life expectancy of around 85 years, reach menopause every year in Germany. The challenge is therefore to find a therapy with few side effects which could improve the quality of life of women with menopausal symptoms. The aim of hormone therapy (HT) is to remedy hormone deficiencies using substances that offer the best trade-off between benefits and risks. This is where progesterone has a new and important role to play. Progesterone is one of the most important gestagens. Biologically effective progesterone formulations created with micronization techniques have been used in clinical practice since 1996. Nevertheless, up until 2003 preference was given to synthetic gestagens rather than progesterone. The increased breast cancer hazard ratio of 1.23 reported in the WHI study and of 2 given in the Million Women Study has been associated with the use of synthetic gestagens. In a comparison between synthetic gestagens and progesterone, the E3N Study showed that the transdermal administration of estrogen and progesterone did not lead to an increase in breast cancer rates (RR: 1.08). The administration of progesterone does not change the HDL/LDL cholesterol ratio. Because of its anti-mineralocorticoid effect, progesterone has no impact on carbohydrate metabolism, hemostasis, blood pressure, thrombogenicity and body weight. The administration of 200 mg/day progesterone over 12 days of a menstrual cycle or a daily administration of 100 mg combined with an estrogen are a safe and well-tolerated option to treat menopausal symptoms, with a better benefit risk profile compared to synthetic gestagens.

[Antibiotic prophylaxis in cesarean section -- piperacillin versus piperacillin/tazobactam in 300 cesarean sections]. / Antibiotikaprophylaxe bei Sectio Caesarea -- Piperacillin 4 g versus Piperacillin/Tazobactam 4.5 g.

INTRODUCTION: Antibiotic prophylaxis is a standard procedure in obstetric surgery and has been discussed in various investigations. Use of treatment is judged by high efficacy and good tolerance. METHOD: In 300 patients undergoing cesarean sections we compared results of application of Piperacillin 4 g and Piperacillin/Tazobactam 4.5 g after cut of umbilical cord. Tazobactam/Piperacillin is a combination of a broad-spectrum penicillin and a beta-lactamase inhibitor with increased toxicity against staph. aureus, enterobacter, and other germs responsible for local and systemic infections in obstetric surgery. RESULTS: We did not observe any severe adverse effects. Rate of severe wound infections was 1.3 % (Tazobactam/Piperacillin) and 2 % (Piperacillin alone). The difference showed no statistic significance (p > 0.01). During postoperative course we found a higher increase of CRP (p < 0.01) in the Piperacillin group. CRP proved to be a useful objective parameter to distinguish between patients with or without postoperative infections. No differences were found in the number of leucocytes, time in hospital and other parameters.

Modes of application of gonadotropin-releasing hormone agonists for endometriosis treatment.

Gonadotropin-releasing hormone (GnRH) agonists have gained extensive clinical use, ranging from reproduction to oncology. There are many clinically available GnRH agonists and these can be used via various methods of delivery, ranging from nasal application to daily subcutaneous injection and various forms of depot preparations. The depot preparations are available as once-monthly intramuscular or subcutaneous injections or 3-month depot moieties. In addition, there is also a 1-month subcutaneous implant available. However, the mode of action of all preparations is identical. The question arises of whether or not the mode of application is important for the treatment effects of endometriosis. Indeed, the course and extent of circulating serum estradiol level are different when comparing nasal with depot preparations. The serum estradiol concentration decreases more rapidly and distinctly with depot than with nasal preparations. Over a period of 24 weeks, the levels of serum estradiol remain higher under nasal GnRH agonist treatment, compared with the depot preparations. Histomorphological changes, such as gland diameter, gland area, cytoplasm and nuclear area, and stromal extension, change less with nasal GnRH agonist therapy than under depot GnRH-agonist treatment. This is also reflected in the spectrum and severity of side effects of nasal and depot preparations. Side effects were more prominent with depot preparations. In addition, bleeding/spotting control was better with the depot preparations. Furthermore, depot preparations had a lower recurrence rate and the time till recurrence was longer. In addition, subsequent surgical and/or medical treatments were significantly less often required with depot preparations (p < 0.05).

Morphometric analyses of endometriotic tissues to determine their grade of activity.

The last revised classification of endometriosis of the American Fertility Society takes the extension of endometriotic lesions and the three macroscopic appearances of this disease into consideration. The aim of this study was to determine whether morphometric analyses are able to describe the grade of activity of endometriotic lesions according to their macroscopic-morphological appearances. Endometriotic samples of 45 patients were analyzed morphometrically using a semiautomatical planimeter. Six different parameters were investigated: the cytoplasmic surface of epithelial cells, the nucleus surface of epithelial cells, the nucleus surface of stromal cells, the gland surface, the gland circumference and the gland diameter. No statistically significant differences (p > 0.05) between the macroscopic appearances of the endometriotic lesions and the six analyzed morphometric parameters were found. The majority of the endometriotic lesions showed median values for the cytoplasmic surface of epithelial cells, the nucleus surface of epithelial cells and the gland surface that did not differ from the median values of all tissues, independently of the macroscopic appearances of these lesions and of the corresponding serum hormonal levels of 17 beta-estradiol and progesterone that were measured at the time of biopsy (p > 0.05). Our morphometric data showed that the red and so-called 'active' endometriotic lesions did not exhibit different morphometric characteristics from the so-called 'inactive' black or white lesions. We found that white and black lesions showed in some cases higher morphometric values than the mean values, so that these macroscopic appearances of endometriotic lesions cannot be considered as 'burned-out' endometriotic tissues. Therefore, black or white endometriotic lesions also have to be considered as therapeutically relevant, as they cannot be defined as 'inactive' endometriosis.

Peritoneal endometriosis: validation of an in-vivo model.

BACKGROUND: The current medical treatment of endometriosis, a common gynaecological disease, is still associated with a high recurrence rate. To establish an appropriate in-vivo model to evaluate new therapeutic strategies we validated the nude mouse model for the intraperitoneal cultivation of human endometrial tissue. METHODS: Human endometrium of the proliferative phase was implanted into the peritoneal cavity of normal cycling and ovariectomized athymic mice and of cycling non-obese diabetic (NOD)-severe combined immuno-deficiency (SCID) mice. Morphology, proliferation, differentiation, and angiogenesis in the ectopic endometrium at different time points after implantation was investigated. RESULTS: Adhesion of endometrial fragments was observed from day 2 onwards. The lesions persisted for up to 28 days revealing a well preserved glandular morphology. The glandular epithelium maintained cytokeratin expression even after 14 days of culture. With progressing culture, glands exhibited vimentin staining in combination with a decrease of surrounding stromal cells. Proliferation of glandular epithelium could be demonstrated throughout the investigated period of 28 days, whereas expression of oestrogen and progesterone receptors was maintained only in endometriotic lesions grown in cycling but not in ovariectomized mice. Neoangiogenesis occurred from day 4 onwards, independent from the intraperitoneal localization of the ectopic lesions. CONCLUSIONS: This in-vivo model is a promising tool to test the effect of compounds such as different hormone agonists/antagonists or anti-angiogenic factors to develop new therapeutic concepts in endometriosis.

Prospective randomized study comparing the GnRH-agonist leuprorelin acetate and the gestagen lynestrenol in the treatment of severe endometriosis.

Endometriosis is thought to be an ovarian-dependent benign disease that affects up to 12% of women during their reproductive life. For the past ten years the gonadotropin-releasing hormone (GnRH)-agonists have been proved effective and safe drugs in the treatment of endometriosis. Nevertheless, gestagens such as lynestrenol still remain the most often used hormonal drugs for the treatment of this disease. The primary objective of this study was to compare the efficacy of the GnRH-agonist leuprorelin acetate depot (LAD) (Enantone-Gyn) 3.75 mg subcutaneously per month with that of the gestagen lynestrenol (LYN) (Orgametril) 5 mg orally twice per day in women with severe endometriosis, in terms of postoperative revised American Fertility Society (r-AFS) scores I-IV at first-look laparoscopy (score after removal of endometriotic lesions or adhesions) to the r-AFS score after six months' treatment. Secondary objectives were the improvement of clinical symptoms and the side-effect profile. Forty-eight women with postoperative r-AFS scores I-IV were evaluated in an open prospective randomized study between 1996 and 1998. All the participants underwent a first-look laparoscopy with resection of endometriotic lesions and six months' therapy with one of the above mentioned drugs, and a further second-look laparoscopy. The six months' treatment with LAD or LYN led to a significant reduction of the r-AFS score points in both groups. The mean r-AFS score in points for the LAD group after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group. After the medical treatment a mean value of 11.5 points was observed in the LAD group compared with a mean value of 25.5 in the LYN group. This difference was statistically significant (p = 0.000014, Wilcoxon test). The improvement in the symptoms of dysmenorrhea, chronic pelvic pain and dyspareunia was also more pronounced in the LAD-treated group. LAD was more effective than LYN in the suppression of circulating serum 17 beta-estradiol levels after 6 months of treatment (mean 27.7 +/- 9.3 pg/ml versus 42.6 +/- 59.3 pg/ml). All the observed side-effects were deemed tolerable by the women who participated in this study. As the reduction of the r-AFS score in points was much more pronounced in the LAD group than in the LYN group, GnRH-agonists should therefore be used as first-choice drugs in the treatment of endometriosis. Due to the limited treatment of 6 months' duration of GnRH-agonists, gestagens might be used as second-line drugs for long-term and continuous treatment in the management of endometriosis to maintain the primary beneficial effect of GnRH-agonist treatment in patients who have completed their families.

[Liposuction for "body contouring" in gynecology]. / Der Einsatz der Liposuktion zum "body contouring" in der Gynäkologie.

OBJECTIVES: The aim of this study was to describe the possible use of the ultrasound-assisted liposuction and liposuction with the tumescent technique for the contouring and remodelling of superficial fat areas of women in the field of gynaecology. PATIENTS AND METHODS: Between 1997 and 1999 85 healthy female patients underwent a liposuction in the department of gynaecology of the university of Essen. The patients were divided into two groups. Thirty patients (group 1) underwent an ultrasound-assisted liposuction whereas the remaining 55 patients (group 2) were operated using only the tumescent technique. RESULTS: From the operated 582 body areas a large volume liposuction with the aspiration of more than 1,000 cc fat was performed in 48.2% of the cases. In the remaining 51.8% of the cases aspiration volumes between 300 and 1,000 cc fat were obtained. No statistically significant differences could be observed when comparing the aspirat volumes between both treatment groups (p > 0.05). Serious complications were not observed. DISCUSSION: Our data could show, that liposuction is an extremely safe method for eliminating surperficial fat depots in the sense of body contouring in gynaecology, but that it should not be used for the reduction of obese body volumes. If ultrasound-assisted liposuction is really superior to liposuction with the tumescent technique remaining uncertain, no time gain could be observed due to this technique.

Expression of the gap junction connexins Cx43, Cx45 and Cx26 in human uterine leiomyomata.

Uterine leiomyomata of 34 premenopausal women undergoing leiomyomectomy or hysterectomy, and in four cases the corresponding myometrium, were collected at laparotomy or laparoscopy to investigate the ability of these benign smooth muscle cell tumors to express different connexins. Immunohistochemical and Northern blot analyses were performed for the characterization of the expression of connexins Cx43, Cx45, Cx26 and Cx32. Immunofluorescence revealed the presence of Cx43 in most leiomyomata. Only seven leiomyomata lacked Cx43 expression. Cx45 was expressed in 13, a weak Cx26 immunostaining was found in seven cases, whereas Cx32 could not be detected. No correlations between the 17 beta-estradiol or progesterone serum levels and the expression patterns of the connexins Cx43, Cx45 and Cx26 could be observed. Gonadotropin-releasing hormone (GnRH)-agonist or progestin treatment did not influence the connexin expression pattern. Northern blot analyses confirmed these results; however, transcripts of Cx26 were not detectable. Connexin transcripts between myomata and the corresponding myometrium showed no obvious differences. Our data show that uterine leiomyomata are capable of expressing different connexins comparable to the corresponding myometrium, but do not respond to different hormonal conditions. The ability to express the appropriate connexins could explain why these tumors, though developing independently of hormonal levels, are still differentiated benign smooth muscle tumors.

Early treatment of endometriosis with GnRH-agonists: impact on time to recurrence.

In a study, 52 patients with histologically confirmed endometriosis underwent a "three-step" therapy. The follow-up period was up to 60 months (median 33.5 months). If r-AFS-score was posttherapeutically 0, recurrence occurred latest after 36 months (median 18 months), if stage III was found posttherapeutically, recurrence occurred already latest after 18 months (median 8 months), (log-rank test P=0.0072). In our study we could confirm a clear relationship of recurrence of symptomatic endometriosis to the post-therapeutically achieved r-AFS-score.

E- and P-selectin expression in endometriotic tissues and the corresponding endometria.

Endometriosis is one of the most frequent diseases in gynecology. It is histologically defined as a non-malignant pathology in which endometrial-like tissue is found outside the uterus. The pathogenesis and mechanisms involved in the development of endometriosis-associated pain symptoms are still under investigation. A local peritoneal inflammation seems to play an important role in the origin of these symptoms. Selectins belong to a group of cell adhesion molecules that mediate the localization of circulating leukocytes on the endothelium at the sites of inflammation. The aim of this study was to investigate the expression of E- and P-selectins in endometriotic tissues and the corresponding endometria. Thirty endometriotic samples, 13 corresponding endometria and six endometria of patients without endometriosis were analyzed using an immunohistochemical technique. Just two endometriotic tissues expressed E-selectin, while five samples were positive for P-selectin. The selectin expression of the corresponding endometria was also very weak. No correlations between the revised American Fertility Society (rAFS) score or the hormonal situation of the patients at the time of biopsy and the selectin expression could be found. In conclusion, the selectin expression in endometriotic glands does not play an important role in the initiation of inflammatory processes caused by endometriosis. This inflammation must be considered as a secondary reaction after the implantation of the endometriotic glands, so that endometriotic tissues are not able to induce, by the expression of selectins, a direct inflammation.

[Long-term side-effects following cyproterone acetate containing therapy in gynecology]. / Langzeitnebenwirkungen nach cyproteronacetathaltiger Therapie in der Gynäkologie.

It has been suggested that cyproterone acetate (CPA) has a mutagenic potency. It has been postulated that a threshold dosage of CPA has mutagenic effects, but in the same way data have been published documenting that a continuous low dosage of cyproterone acetate leads to a reduction of mutagenic episodes. Despite published data about higher levels of DNA adduct creations due to CPA an international multicentre study analysing 2,506 patients with 7,971 patient-years that used CPA could not find any liver cell cancers, even if due to epidemiological data 6 liver cell cancers should have occurred upon this study group. The present study deals with the evaluation of 57 women which received CPA in combination with EE2 11-13 years before. The daily dosage was 2 mg CPA in combination with 35 mg or 50 mg EE2. In Germany these drugs were registered under the name of Diane 35 or Diane 50. Long-term follow-up evaluation concerning side effects, especially the appearance of liver cell carcinomas, were the aim of this study. With the records of 32% (18/57) of the above mentioned patient group the following long-term follow-up side effects could be observed: 1) weight gain, 2) headache, 3) migraine, 4) gastrointestinal disorders, 5) mood affections/depressions, 6) oedema of the legs, 7) skin affections, 8) mastodynia. No benign liver tumor or liver cell carcinoma was detected upon our group of investigated patients. In conclusion we can affirm that the use of CPA in a dosage of 2 mg per day does not lead to serious side effects under long-term follow-up observation conditions and that it's use does not correlate with a higher appearance of liver cell carcinomas.

Reduced proliferation and cell adhesion in endometriosis.

Endometriosis is defined as endometriotic tissues growing outside the uterine cavity. The cell biological processes responsible for the pathogenesis of this disease are not well understood. In order to detect differences in proliferative activity between endometria and endometriotic lesions, Ki67 staining was analysed. In addition, expression of epidermal growth factor (EGF) and its receptor was examined using immunohistochemistry. For dedifferentiation processes pointing to invasive properties of the uterine epithelium, the presence of the adhesion complex E-cadherin with the associated alpha- and beta-catenin was investigated. Specimens of endometrium in the proliferative phase of 36 patients without, and 79 patients with, endometriosis together with endometriotic lesions were studied. The study revealed a significantly reduced proliferation activity in uterine epithelium within the ectopic lesions but no differences between eutopic endometria of non-affected and affected patients. Furthermore, a lower expression of both EGF and its receptor in the epithelial cells of the ectopic glands was observed. The adhesion complex E-cadherin, together with alpha-, and beta-catenin, was slightly reduced in uterine epithelial cells of women with endometriosis and less expressed in endometriotic lesions. The results indicate that epithelial cells of endometriotic lesions are not hyperproliferative, but do appear to dedifferentiate, displaying an invasive character.

[Efficacy and safety of two cephalosporins in the perioperative prophylaxis in patients undergoing abdominal or vaginal hysterectomies or gynaecological laparotomies: a prospective randomized study]. / Wirksamkeit und Verträglichkeit zweier Zephalosporine in der perioperativen Antibiotikaprophylaxe bei abdominalen und vaginalen Hysterektomien und gynäkologischen Laparotomien. Eine prospektiv randomisierte Studie.

The aim of this study was to compare efficacy and safety of perioperative antibiotic prophylaxis in patients undergoing abdominal or vaginal hysterectomy or gynaecological laparotomy to improve the prevention of surgical wound infections. One hundred and ninety-nine patients were prospectively randomized into two groups: the first group (n = 100) received perioperative prophylaxis using 1 g cefotiam (Spizef) and 0.5 g metronidazole (Clont) intravenously 30 min before surgery, whereas the second group (n = 99) was treated with 2 g cefoxitin (Mefoxitin) intravenously, also 30 min before surgery. The efficacy of the perioperative antibiotic prophylaxis was assessed clinically and on the basis of laboratory parameters. No wound infections were observed in 97 patients (97%) of the cefotiam-treated group and in 94 patients (94%) of the cefoxitin-treated group. No systemic postoperative infections were observed in 81% of the patients treated with cefotiam combined with metronidazole and in 85% of the patients treated with cefoxitin. The good tolerability of the drugs administered was proven in 98% of the patients treated with cefotiam and metronidazole and in 97% of the patients treated with cefoxitin. In both groups 3 patients developed nausea and/or vomiting, respectively, due to the antibiotic prophylaxis. A low infection rate after gynaecological surgery was observed. Cefotiam as a low dosage combined with metronidazole was as effective as cefoxitin. Cephalosporins of the second generation in combination with metronidazole can, therefore, be considered effective and safe drugs in the prevention of postsurgical infections.

[Endometriosis: clinical, histological and morphometric findings before and after Gn-RH agonist therapy]. / Endometriose: Klinische, histologische und morphometrische Befunde vor und nach Gn-RH-Agonisten-Therapie.

After bioptical diagnosis of endometriosis, 81 patients were treated with GnRH-agonists buserelin or leuprolide for six months. Biopsies before and after treatment were used to test a semiquantitative score-system, regarding atrophy of glands and stroma cells. Furthermore glandular diameter, circumference and area of nuclei were examined morphometrically using a microscopic semiautomatical measuring system. Morphometrical and histological alterations during therapy were evaluated. Additionally, data suitable for predicting a possible therapeutic success were described. After therapy 40 patients still showed endometriotic implants (partial responder) in contrast to 41 cases without foci (total responder). Therapeutic effect of GnRH-agonists was proved in every respect: clinical complaints decreased markedly during GnRH-agonists therapy. Both buserelin and leuprolide treated groups revealed increase of atrophy and reduction of extension of stroma. Correspondingly morphometrical analysed parameters such as diameter, circumference and area of glands decreased during therapy as well as area of cytoplasm and nuclei. Except the diameter of glands, the leuprolide treated partial responder group (residual foci after GnRH-therapy) revealed a stronger therapeutic effect than the buserelin treated partial responder group. Obviously this effect seems to be produced by the stronger estradiol suppression of leuprolide. Pretherapeutic comparison of measured values pointed out a minor distinct endometriosis in the total responder group. Success or failure of therapy seems to depend more on the pretherapeutic degree of expression of endometriosis. Obviously the kind of applicated GnRH-agonist plays a minor distinct role. Morphometrical data of endometriotic foci appear to be appropriate to predict a possible therapeutic success of GnRH-agonist therapy. But because of many exceptions only a roughly estimated prediction is possible.

Expression of the cell adhesion molecules ICAM-1 and VCAM-1 in the cytosol of breast cancer tissue, benign breast tissue and corresponding sera.

OBJECTIVE: Cellular adhesion molecules ICAM-1 and VCAM-1 have been implicated in tumor progression and metastasis. As the sequential interaction of neoplastic cells with the endothelium of tumor neovascularisation is believed to be essential for tumor metastasizing processes, we analysed the concentration of ICAM-1 and VCAM-1 in the cytosol of patients with human breast cancers and their corresponding sera. We compared the obtained values with established prognostic parameters for breast cancer. Benign breast tissues were also analyzed. PATIENTS AND METHODS: Levels of ICAM-1 and VCAM-1 of 62 patients with invasive breast cancer and 17 patients with benign breast tissue were measured using commercially available sandwich enzyme-linked immunoassays with monoclonal antibodies. To establish a reference and control group, levels of ICAM-1 and VCAM-1 were measured in the sera of 66 women without breast tumors. RESULTS: The mean cytosol concentration of ICAM-1 and VCAM-1 was significantly higher in the breast cancer specimens than in the tissue of patients with benign breast diseases. This could be found not only in the tumor cytosol but also in the corresponding sera of the patients. No correlations between the ICAM-1 and VCAM-1 expressions and established prognostic parameters could be observed. CONCLUSIONS: Our findings suggest that malignant breast cancer cells could induce neovascularisation with subsequent high expressions of ICAM-1 and VCAM-1. These upregulations of adhesion molecules might contribute to changes in invasive phenotypes by promoting endothelial cell adhesion and angiogenesis, as well as being responsible for the recognition of tumor cells by the human immune system. Prognostic relevance for the development of breast cancer could not be established.

Expression pattern of integrin adhesion molecules in endometriosis and human endometrium.

Integrins are cell adhesion molecules that undergo cell-specific dynamic changes during the normal menstrual cycle in the human endometrium. Here, using immunohistochemistry, we have investigated the expression pattern of the integrins alphav, alpha2beta1, alpha3beta1, alpha3, alpha6, beta1, beta2 and beta3 in the human ectopic endometrium of 30 patients and in nine cases in the corresponding eutopic endometrium. The biopsies were obtained during the early or late follicular phase (25 cases), during the corpus luteum phase (four cases) and in one case after 6 months' treatment with a gonadotrophin releasing hormone (GnRH) agonist. The integrin expression was independent of the ovarian steroid situation at the time of biopsy. The integrin alpha6 was expressed in all endometriotic and endometrium samples. The integrin alpha3 was absent in all endometrium tissues of patients with endometriosis. However, the corresponding endometriotic lesions re-expressed this adhesion molecule in 15 cases. No change in integrin beta3 expression pattern could be demonstrated in either endometriotic lesions or endometrium samples, regardless of the menstrual cycle phase. A correlation between serum oestradiol and progesterone concentrations and the expression of the investigated integrins was not observed, thus indicating that these two hormones play a minor role in the regulation of the cell adhesion molecules examined. Our investigation suggests that endometriosis is a dedifferentiated disease as it expressed different integrins in comparison with the eutopic endometrium, and independently of the hormonal situation. The ability of endometriotic tissues to express integrins may explain the high recurrence rates in patients with endometriosis, as these samples retain their adhesion potency after retrograde menstruation and are thus able to establish cell-cell and cell-matrix interactions with the surrounding peritoneum.

Long-term follow-up on the treatment of endometriosis with the GnRH-agonist buserelinacetate. Long-term follow-up data (up to 98 months) of 42 patients with endometriosis who were treated with GnRH-agonist buserelinacetate (Suprecur), were evaluated in respect of recurrence of pain symptoms and pregnancy outcome.

OBJECTIVE: In our previous study, 119 patients with histologically confirmed endometriosis underwent a 'three-step' therapy between 1987 and 1989, where surgical removal of endometriosis was followed by a 6 month treatment with 3 x 300 microgram buserelinacetate daily intranasally and a second look laparoscopy or laparotomy with removal of residuals. Long-term follow-up data in respect of recurrence of symptoms and pregnancy outcome were investigated. STUDY-DESIGN: Long-term follow-up data of 42 out of 119 treated patients on the post-treatment effect were obtained using a special questionnaire. Recurrence of dysmenorrhea, dyspareunia and pelvic pain was defined as recurrence of disease. The follow-up period was up to 98 months with a median time of 82.5 months. RESULTS: Out of the 42 patients, 23 complained of infertility. Fourteen out of these 23 patients became pregnant during the follow-up period, resulting in 23 pregnancies with 18 newborns, 4 miscarriages and one ectopic pregnancy. Ten patients conceived spontaneously, stimulation program became necessary in the rest of patients. Twenty-eight of the 42 patients complained recurrence of symptoms with median first onset at 10.7 months. Improvement on quality of life and subjective conditions were reported by 30 patients. CONCLUSIONS: Our study suggests that the 'three-step' therapy of endometriosis with GnRH-agonist buserelinacetate leads to a significant improvement on the quality of life and well being in the majority of the patients and to a high pregnancy rate. This treatment represents a favourable approach in the management of endometriosis.

Uterine leiomyomata and sterility: therapy with gonadotropin-releasing hormone agonists and leiomyomectomy.

The aim of this study was to obtain data about the pregnancy rate in patients with uterine leiomyomata after treatment with gonadotropin-releasing hormone (GnRH) agonists followed by myomectomy. Between 1987 and 1993, 61 patients with uterine leiomyomata and sterility underwent 6 months' GnRH agonist treatment, in part with a surgical intervention. Sixty-two per cent of the patients suffered from concomitant endometriosis. After hormonal therapy 41 patients underwent a myomectomy. According to sonographic and clinical criteria, there was no indication for the enucleation of the leiomyomata for the remaining 20 patients. Owing to the combined therapy, consisting of primary treatment of uterine leiomyomata with GnRH agonists, followed by surgical intervention, 25 patients (41%) suffering from long-term sterility (average 4 years) became pregnant. An early abortion occurred in only three cases (12%). No patient who underwent a myomectomy developed new myomata during the following pregnancy. Four patients suffering from a single leiomyoma became pregnant within the first 3 months after myomectomy, all of them conceiving spontaneously. Considering the high rate of spontaneous conceptions and the low abortion and complication rates during pregnancy, the combined therapy of GnRH agonists followed by myomectomy represents a major step forwards in the effective treatment of sterility in patients with uterine leiomyomata.