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.

10-month retrospective study on compliance and tolerability of the drospirenone-only pill.

OBJECTIVE: The current study evaluated menstrual bleeding profiles, compliance and tolerability in women using a drospirenone (DRSP)-only pill. PATIENTS AND METHODS: This is a non-interventional, retrospective, multi-center study on healthy female adults [n=276, aged between 18 and 53 years and premenopausal using a DRSP-only pill for at least six months with a mean duration of 10.4 months (+/-SD 4.0) months]. 75.6% used other contraceptives than POP before starting with the DRSP-only pill. A questionnaire was used to evaluate the bleeding profile. 56.5% of the women had associated cardiovascular risk factors. RESULTS: Two hundred and sixty-two (262) women (mean age of 32.5 ± 9.1 years; mean BMI of 23.1 ± 3.8 kg/m²) were eligible for analysis. 42.6% of the users had a scheduled bleeding, 33,3% unscheduled bleeding and 48% no bleeding during the last evaluable cycle. 75.4% evaluated the bleeding profile in the last cycle as very good or good, 13.8% said there was no change since starting the medication, 8.4% declared the profile was bad and 2.3% as very bad. 87.8% of the users evaluated the general satisfaction of the contraception as very good or good, whereas only 8.8% and 3.4% said there was no change or that it was bad. No women evaluated the general satisfaction as very bad. CONCLUSIONS: These data demonstrate that the DRSP-only pill is associated with a very high satisfaction as a contraceptive in general and in the individual bleeding profile. These aspects reaffirm the acceptability not only in women with cardiovascular risk factors.

Multicenter, international observational study on quality of life and acceptability of a vaginal contraceptive ring containing etonogestrel/ethinylestradiol 11.00/3.474 mg over six months of use.

OBJECTIVE: The current post-market study aimed at analyzing women's menstrual bleeding intensity, vaginal infections, and quality of life parameters using the contraceptive vaginal ring Ornibel®. PATIENTS AND METHODS: In Germany and Spain, a multicenter study of healthy female adults (n=211) aged 18 to 45 used the vaginal ring Ornibel® for at least six months. Data collection was conducted using a patient questionnaire. The menstrual bleeding intensity was analyzed using visual analog scales (VAS). A Chi-square linear trend test assessed associations between quality-of-life parameters and continuation and recommendation of vaginal ring use. RESULTS: Three out of four women experienced six menstrual bleedings during the first six months of using the vaginal ring, with a median duration of four days during the study. The use of the vaginal ring led to a significant reduction in menstrual flow intensity (from 60 VAS points to 40 VAS points, p<0.001). In the German cohort, it was shown that dysmenorrhea and unscheduled bleeding and spotting were reduced with the use of Ornibel® as well. Most women (93.7%) agreed or strongly agreed that the vaginal ring was easy to insert, and its use was rated as comfortable or very comfortable by 97.5%. Both parameters were significantly associated with the continuation of the ring (easy to insert p=0.01, feeling comfortable: p=0.002) or its recommendation (easy to insert p=0.002, feeling comfortable: p=0.002). CONCLUSIONS: The observational data demonstrate that the contraceptive vaginal ring provides high acceptability and comfort. It is a well-accepted contraceptive method characterized by high efficacy and positive effects on cycle control.

Evaluation of the food effect on a drospirenone only contraceptive containing 4 mg administered with and without high-fat breakfast in a randomised trial.

BACKGROUND: The objective of the present trial was to assess the difference in pharmacokinetics (PK) of an oral test preparation containing 4 mg drospirenone (DRSP) under fasting conditions compared to PK upon food intake after single dose administration. METHODS: Open label, single centre, two-treatment, two-sequence, crossover study in 24 healthy female volunteers, with duration of 1 day per sequence and with a real wash-out period of 14 days to investigate the relative bioavailability of DRSP with both forms of administration. The 90% confidence intervals (CI) were calculated for the intra-individual ratio (test with food vs. without food) of the PK endpoints Area under the curve; 0-72 h [AUC(0-72 h)] and maximal plasma concentration [Cmax] of DRSP. RESULTS: The 90% CI calculated by analysis of variance using logistic transformation (ANOVA-log) for the endpoint, intra-individual ratio (Test 'A' = with food intake) vs. Test 'B' = without food intake) of AUC(0-72 h) of drospirenone was between 104.72 and 111.36%. The 90% CI calculated by means of ANOVA- log for the endpoint intra-individual ratio (Test 'A' vs. Test 'B') of Cmax of DRSP was between 118.58 and 141.10%. The mean relative bioavailability of the test with food 'A' compared to the Test without food 'B' after single dose administration based on the endpoints AUC(0-72 h) was 107.99%; for the endpoint Cmax it was 129.35%. CONCLUSIONS: The rate of absorption, based on the endpoint Cmax of DRSP was increased by about 30% under fed conditions. With respect to consumer habits, this may represent a relevant benefit for contraceptive safety, as the time span between food consumption and pill intake does not play a role. IMPLICATIONS: Our results suggest that the food intake has no impact on the absorption of 4 mg DRSP in the management of contraception. This increases the contraceptive efficacy as no interference with food is expected when consuming the oral formulation under real life conditions. TRAIL REGISTRATION: Trial registration number: EudraCT-No: 2012-004,309-28.

Comparative dissolution profiles of two anti-emetic delayed release dosage forms of doxylamine and pyridoxine: Xonvea® tablets vs. Cariban® capsules.

OBJECTIVE: Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose combination of doxylamine and pyridoxine has been proven safe and effective although the mechanism of action is not well established. There are different pharmaceutical dosage forms in the European market. The objective of this study was to compare the characteristics of a capsule formulation, Cariban® and a tablet formulation, Xonvea® to evaluate the potential impact of their release profiles on their onset of action. MATERIALS AND METHODS: 10 mg/10 mg of doxylamine succinate/pyridoxine hydrochloride capsules (Cariban®) and tablets (Xonvea®) were used as reference materials. Appearance, mass, composition, and in vitro dissolution profiles were compared. Bibliographic data from 4 pharmacokinetic studies of Xonvea® and 1 pharmacokinetic study of Cariban® was reviewed. RESULTS: In vitro dissolution studies showed significant differences in dissolution profiles of tablets and capsules. The later exhibiting some release of both drug substances in acid conditions followed by a non-complete release after a total of 3 hours while the tablets demonstrated gastro-resistant properties and rapid API release in about 20-30 minutes after the acid stage. Comparison of PK data showed greater Cmax for pyridoxine. CONCLUSIONS: At pH 6.8, complete and faster release of the fixed dose combination for Xonvea® gastro-resistant tablets compared to Cariban® capsules could possibly explain the greater Cmax observed in vivo for the tablet's formulation. This could translate into faster onset of action and relief of nausea for pregnant women taking the tablets vs. the capsules.

Drospirenone 4 mg in a 24/4 regimen maintains inhibition of ovulation even after a 24-h delay pill intake - Pharmacological aspects and comparison to other progestin-only pills.

This review focuses on the pharmacological and inhibition of the ovulation of progestin-only, estrogen-free contraceptive containing drospirenone in a dosage of 4 mg in a regimen 24/4. The USA and European regulatory authorities have approved it. The molecule has anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. This regime improves the bleeding profile, maintains the plasma E2 levels comparable to the menstrual cycle's early follicular phase, avoids hypoestrogenism, and preserves efficacy despite forgetting the tablet intake as drospirenone has a half lifetime of 30-34 hours. Clinical studies have shown good efficacy, very low cardiovascular side effects, and high acceptability and maintenance of ovulation inhibition after scheduled 24-h delays in pill intake. The molecule is compared to other POP like levonorgestrel or desogestrel.

Acute severe SARS COVID-19 patients produce pro-resolving lipids mediators and eicosanoids.

OBJECTIVE: This study aimed to evaluate the eicosanoid and pro resolutive parameters in SARS COVID-19 patients with the severe acute respiratory syndrome. PATIENTS AND METHODS: Fourteen male patients with an acute respiratory syndrome caused by SARS COVID-19 and four healthy controls were evaluated by measuring the following parameters in plasma: Polyunsaturated fatty acids: EPA, DHA, ARA, and DPA. Specialized Pro-resolving mediators (SPMs) (including monohydroxy-containing precursors 17-HDHA, 18-HEPE, 14-HDHA) resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. RESULTS: Plasma from COVID-19 patients presented higher amounts of pro-inflammatory and pro-thrombotic lipid mediators as compared to healthy subjects (65.7 pg/ml vs. 10.2 pg/ml), including thromboxane (2142.6 pg/ml vs. 10.4 pg/ml), and the ratio between total plasma pro-inflammatory mediators versus total SPM's was 13.2 to 0,4, respectively. CONCLUSIONS: A clear disbalance favoring the pro-inflammatory axis is described, showing the need to perform future clinical interventions in these patients using SPM's or monohydroxylated lipid mediators derivates from fatty acids.

Safety, efficacy and quality of life of the novel vaginal contraceptive ring containing etonogestrel/ethinylestradiol 11.0/3.474 mg after 3 years of "real life" experience.

Combined contraceptive vaginal rings (CVR) are increasingly appreciated due to several beneficial properties like avoidance of the hepatic first-pass effect, a comparatively low dosage of hormones and comfortable use. A further development of the widely used CVR releasing 0.12 mg etonogestrel (ETO) and 0.015 mg ethinylestradiol (EE) per 24 hours has been marketed since 2017. The 11.00/3.474 mg ETO/EE CVR Ornibel® is bioequivalent to the former product but differs in its polymer composition leading to improved stability. Here, results from recent studies on the novel CVR Ornibel® are reviewed including clinical trials on bleeding profile, acceptability, sexual function and other quality of life (QoL) parameters as well as in vitro studies on microbial adhesion to the CVR and the influence of ring rupture on hormone release. Findings are complemented with new data on contraceptive efficacy and safety of the new CVR that were assessed during 3 years of real-life experience.

Bleeding profile of women using a drospirenone-only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg.

BACKGROUND: Progestin-only pills are associated with irregular bleeding pattern including amenorrhea. Desogestrel 75mcg even being a pill that inhibits ovulation shows a poor cycle control that limits a more common use. A drospirenone (DRSP)-only pill was developed to improve the bleeding profile. METHODS: A phase III study in healthy women aged 18 to 45 years was performed to compare the bleeding profile and safety of women taking a DRSP only pill in a regime of 24 days of 4 mg of DRSP tablets followed by 4 days of placebo versus desogestrel 0.075 mg per day continuously over 9 cycles. A total of 858 women with 6691 drospirenone and 332 women with 2487 desogestrel treatment cycles were analyzed. The primary endpoint was the proportion of women with bleeding/spotting days in each cycle from cycles 2 to 9 and cumulative in cycles 2 to 4 and cycles 7 to 9 including and excluding those with amenorrhea. FINDINGS: In each cycle, up to cycle 7, the proportion of women with unscheduled bleeding including those which did not bleed was statistically significantly lower in the DRSP group than in the DSG group (p = 0.0001, chi-square test). The mean [SD] number of unscheduled bleeding and spotting days during cycles 2-9 was statistically significantly lower in the DRSP group than in the DSG group (21.5 [22.86] days vs. 34.7 [33.73] days, p = 0.0003, Wilcoxon-rank-sum-test). Excluding amenorrhoeic women following results were obtained: In the cycles 2-6, the proportion of women with unscheduled bleeding was statistically significantly lower in the DRSP group than in the DSG group (p = 0.0001, chi-square test). The mean [SD] number of bleeding days was 8.6 [8.52] days vs. 12.9 [16.47] days, p = 0.0233. CONCLUSIONS: This report describes the improvement in bleeding profile of women using the new DRSP only oral contraceptive in comparison to DSG providing a better quality of live and adherence to the contraceptive method. EudraCT registration number: 2011-002396-42.

Elution from intact and broken vaginal contraceptive rings: an in vitro study.

OBJECTIVE: The in vitro elution of the active substances etonogestrel (ETO) and ethinylestradiol (EE) of Ornibel® (a vaginal delivery system) was determined after a deliberate breakage of the vaginal contraceptive ring and compared to the standard elution and hormone release of intact rings under the same experimental conditions. MATERIALS AND METHODS: Ornibel® intact and broken vaginal rings were placed in a dissolution buffer and subject to a repetitive sampling of ETO and EE following a standardized in vitro elution (IVE) procedure for 21 days. The hormone dissolution profile was determined by HPLC using a fully validated analytical method. In a second study, rings were broken after day seven, and their elution profiles were compared to that of intact rings. For all utilized batches, the stability conditions established were 24 months at 5°C. Furthermore, no special storage conditions are needed. RESULTS: The instantaneous elution on day 1 of ETO and EE for intact rings were 119±8 µg/day and 15±1 µg/day, respectively (mean ± SD), which was non-significantly different to the immediate release of ETO and EE for broken rings (118±4 µg/day and 14±1 µg/day). The average elution profile for days 2-20 were 132±5 µg/day and 18±1 µg/day (ETO/EE, intact rings) and 132±4 µg/day and 19±1 µg/day (ETO/EE, broken rings) respectively. On day 21, the elution of ETO and EE was numerically similar 111±5 (±4) µg/day and 18±1 µg/day) for both intact and broken rings. The IVE results from intact rings and vaginal rings deliberately cut on day seven similarly did not differ in their release of ETO and EE. CONCLUSIONS: Our study concludes that the hormonal release of ETO and EE from Ornibel® are similar for intact and broken vaginal rings under standardized in vitro conditions.

Comparative pharmacokinetic estimates of drospirenone alone and in combination with ethinyl estradiol after single and repeated oral administration in healthy females.

OBJECTIVE: To determine the pharmacokinetics (PK) of drospirenone (DRSP), alone versus in combination with ethinyl estradiol (EE), after single and repeated administration. STUDY DESIGN: We conducted a single-centre, open-label, crossover, 2-treatment, 2-period, 2-sequence study in which non-micronized DRSP 4 mg or a combination of DRSP 3 mg and EE 0.02 mg were administered to healthy female subjects on day 1 to obtain a single-dose kinetic profile, and from day 4 to day 15 to obtain a repeated-dose kinetic profile. The maximum observed concentration (Cmax) and area under the concentration/time curve (AUC) were determined in a model-independent way using non dose corrected data. Statistical analysis was based on a parametric method (ANOVA-log). RESULTS: A total of 24 healthy female subjects were randomized 1:1 into the study. The mean relative, non-dose-corrected PK estimates after single-dose administration for the endpoints AUC(0-72h), AUC(0-24h) and Cmax were 543.5 ng*h/mL, 296.1 ng*h/mL and 27.3 ng/mL for DRSP alone, and 442.0 ng*h/mL, 264.7 ng*h/mL and 37.5 ng/mL for the DRSP/EE combination; p < 0.001. The mean relative, non-dose-corrected PK estimates after repeated dose administration for the endpoints AUC(0-72h), AUC(0-24h) and Cmax were 1066.8 ng*h/ml, 570.2 ng*h/mL and 41.0 ng/mL for DRSP alone, and 1394.5 ng*h/mL, 732.8 ng*h/mL and 61.4 ng/mL for the DRSP/EE combination; p < 0.001. CONCLUSIONS: DRSP alone exhibits a lower accumulation ratio than together with EE. The extent of systemic exposure at steady-state is about 32% less with the new formulation (AUC(0-24h), steady-state geometric mean ratio: 77.8%; 90% confidence interval: 74.6%-81.1%). This PK profile may be caused by EE. IMPLICATIONS: Our results suggest that metabolic pathways of DRSP can be inhibited by EE resulting in higher DRSP plasma concentrations in DRSP/EE formulations than in a DRSP-alone formulation. The enzymes CYP3A4 and SULT1A1 may play a role. Additional drug-drug-interaction studies are needed to better understand these metabolic pathways and their future clinical implications.

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.