Amenorrhea and BMI as independent determinants of patient satisfaction in LNG-IUD users: cross-sectional study in a Central European district.

OBJECTIVE: This study investigated the satisfaction of women carrying the LNG-IUD and determined influencing factors, especially considering bleeding patterns and body mass index (BMI). DESIGN: Cross sectional study. SETTING: Gynecological offices in a Central European district. PARTICIPANTS: 1825 women aged between 18 and 60 years. MEASUREMENT: While sitting in the waiting room, voluntary patients had to answer a questionnaire about their experiences with the levonorgestrel intrauterine device. One question was used to determine whether the women were current, former or not users of the intrauterine coil. RESULTS: 415 women who had some experiences with Mirena were found. Overall, 266 (65.7%) were "very satisfied," 83 (20.5%) "quite satisfied," 18 (4.4%) "moderate satisfied," 19 (4.7%) "less satisfied," and the same amount "really not satisfied" with the hormonal coil. Women with amenorrhea were more often "very satisfied" in general, than women with hypermenorrhea (178 (67.9%) vs. 3 (1.1%) p < 0.001). Concerning bleeding patterns, 295 (74.1%) were "very satisfied" and 23 (5.8%) "really not satisfied". 203 (91.0%) of all amenorrhoeic women were "very satisfied" with their bleeding patterns, but only 2 (9.5%) of all women with hypermenorrhea (p < 0.001 for α = 0.05). Amenorrhea particularly occurred in women who had a significantly lower body mass index (24.4 ± 4.4 kg/m(2) vs. 27.6 ± 6.5 kg/m(2) in women with hypermenorrhea, p = 0.018 for α = 0.05). After allocating women to the widely used BMI-categories (underweight, normal weight, overweight, obese class I and II) it was evident, that normally weighted women tend toward amenorrhea as well at the beginning of LNG-IUD use as well after 4-5 years of use. In contrast to this, overweighed and obese women tend more often to amenorrhea at the end of use, but not at the beginning (72.7% and 55.6% vs. 25.0% and 0%). Women with a lower BMI were more often "very satisfied" concerning bleeding patterns, but not concerning the general satisfaction. CONCLUSION: Our study showed much evidence, that amenorrhea occurs more often in women with lower BMI contrary to women with a higher one-especially at the beginning of LNG- IUD use. Furthermore amenorrhea was mostly considered to be a positive menstrual change.

Cross-sex hormone therapy alters the serum lipid profile: a retrospective cohort study in 169 transsexuals.

INTRODUCTION: Cross-sex hormone therapy (CSHT) is known to lead to alterations in the serum lipid profile. However, the available reports in the literature are problematic, because of methodological limitations. AIMS: To assess changes in the fasting serum lipid profile during CSHT, including long-term follow-up. METHODS: Retrospective chart analysis of all 89 male-to-female (MtF) and 80 female-to-male (FtM) transsexuals who underwent standard CSHT at the Department of Gynecologic Endocrinology of the Medical University of Vienna (university hospital, tertiary care center), from 1995 to 2009. MAIN OUTCOME MEASURES: The results of the lipid profile were analyzed, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the TC-to-HDL ratio, at the time of treatment initiation (time point "0") and at 3, 12, 24, and 60 months after the start of CSHT. RESULTS: The mean age of patients about to commence CSHT was 35.7 ± 11.4 years (MtF) and 26.0 ± 6.3 years (FtM). For MtF transsexuals, consistent follow-up for 24 and 60 months was available in 83 (93.3%) and 58 (65.2%) patients, respectively; for FtM transsexuals, follow-up was available in 57 (71.3%) and 39 (48.8%) patients, respectively. When testing for an association between the lipid parameters and the time after treatment initiation, significant increases for TG (P < 0.001), TC (P = 0.021), and HDL (P = 0.001) were found for MtF transsexuals, whereas TG, TC, and LDL (P < 0.001) increased and HDL (P < 0.001) decreased in FtM patients. CONCLUSION: Both MtF and FtM transsexuals experience alterations in the serum lipid profile because of CSHT, with the changes in FtM patients possibly more relevant in terms of atherogenesis.

A modified technique of laparoscopic ovarian drilling for polycystic ovary syndrome using the monopolar hook electrode.

The aim of our study was to review our experience with a modified technique of laparoscopic ovarian drilling (LOD) using a monopolar hook electrode. We retrospectively included 38 clomiphene-resistant women with polycystic ovary syndrome undergoing LOD. A laparoscopic monopolar hook electrode was used to make three to six incisions in the ovarian capsule. It resulted in a rate of spontaneous ovulation of 75.8%, an overall one-year pregnancy rate of 80.6% and a subsequent live birth rate of 67.7%. We consider our LOD technique using the monopolar hook electrode practicable. Whether it leads to a more extensive destruction of the ovarian capsule and thereby of the ovarian reserve remains open.

Electron emission and product analysis of estrone: progesterone interactions studied by experiments in vitro.

Recent studies showed that hormones like progesterone, testosterone, etc. can eject [Formula: see text] (solvated electrons). By means of electron transfer processes via the brain, the hormones communicate with other biological systems in the organism. The present study proves that also estrone is able to emit electrons. Their yield strongly depends on the concentration of the hormone, temperature and on the absorbed energy. The metabolites resulting from this process are likewise able to generate electrons, however with much smaller yields. The formation of the estrone metabolites is studied by HPLC-analyses. In vitro experiments with MCF-7 cells demonstrate the distinct effect of progesterone on the carcinogenity of estrone metabolites. Probable reaction mechanisms for explanation of the observed effects are postulated.

Bipolar vessel sealing increases operative safety in laparoscopic-assisted vaginal hysterectomy.

BACKGROUND: To compare laparoscopic-assisted vaginal hysterectomy (LAVH) with and without bipolar vessel sealing (BVS) using the LigaSure™ device by meanings of intra- and postoperative course. METHODS: In a retrospective case-control study 362 female patients (mean age 54.3 ± 9.5 years) were included who underwent LAVH with (n = 252) and without (n = 110) use of BVS. Intra- and postoperative courses and adverse events were evaluated. RESULTS: A shorter mean operating time was found for LAVH with the use of BVS (65.28 ± 16.33 min) when compared with LAVH without the use of BVS (83.73 ± 21.53 min, P < 0.005). The mean postoperative stay did not differ significantly between the two groups (P > 0.05); 15 out of 251 (6.0%) patients were found to have adverse events during or after LAVH with the use of BVS in contrast to 16 out of 110 (14.5%) patients during or after LAVH without the use of BVS (P < 0.05). Following the use of BVS significantly less patients reported postoperative pain for more than 7 days after the operation in contrast to the use of sutures (0/251 [0%] vs. 3/110 [2.7%], respectively, P < 0.05). CONCLUSION: The use of LigaSure™ is effective in decreasing operating time, the overall complication rate and postoperative pain.

Family incidence of endometriosis in first-, second-, and third-degree relatives: case-control study.

BACKGROUND: Initial publications examining the hereditary aspects of endometriosis appeared in the early seventies and demonstrated an up to seven-fold risk for endometriosis in first-degree relatives of endometriosis patients. The aim was to evaluate the influence of hereditary aspects on the endometriosis risk in our patient collective. METHODS: In a retrospective cohort study we evaluated the incidence of endometriosis among first-, second-, and third-degree relatives of endometriosis patients and compare it with its incidence among first-, second-, and third-degree relatives of patients without endometriosis. RESULT(S): Eighty patients in whom endometriosis had been confirmed laparoscopically and histologically by biopsy and 60 patients in whom no endometriosis had been found during laparoscopy were given a questionnaire about the presence of symptoms associated with endometriosis and its family incidence. Patients of both the endometriosis and the control group were 37.7 +/- 6.2 and 45.9 +/- 12.0 years of age at the time of the interview, respectively (p < 0.05). Information about the presence of endometriosis was more readily available for relatives of those in the endometriosis group than for those in the control group (325/749 [43.4%] vs. 239/425 [56.2%], p < 0.05). In 5/136 (3.7%) and 8/134 (6.0%) first-degree relatives of endometriosis patients and the control group, respectively, information about the presence of endometriosis was not available (p = 0.554). Endometriosis was found in 8/136 (5.9%) first-degree relatives of patients and in 4/134 (3.0%) first-degree relatives of controls in the real-case analysis (p = 0.248). When comparing endometriosis characteristics between endometriosis patients with and without a history of familial endometriosis, no significant differences were found. CONCLUSION(S): There is a trend toward an increased familial incidence of endometriosis. In contrast to the literature, we found a less dramatic increase in familial risk for the development of endometriosis.

Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study.

BACKGROUND: Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin. SETTING: Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. RESULTS: The rate of twin pregnancies did not differ between the CC group (12.5%), the LOD group (7.5%), and the metformin only group (2.5%, p=0.239). Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40), followed by the LOD group (45.0%, 18/40), and the metformin only group (47.5%, 19/40; p=0.047). CONCLUSIONS: CC, but not LOD, increases the complication rate in pregnant patients who received metformin.

Reproductive outcome after hysteroscopic septoplasty in patients with septate uterus--a retrospective cohort study and systematic review of the literature.

BACKGROUND: Septate uterus, one of the most common forms of congenital uterine malformations, negatively affects female reproductive health. METHODS: In a retrospective cohort study, we evaluated the reproductive outcome after hysteroscopic septoplasty in 64 women with septate uterus and primary or secondary infertility. We performed a systematic review of studies evaluating the reproductive outcome after hysteroscopic septoplasty. RESULTS: Sixty-four women underwent hysteroscopic septoplasty. In 2/64 (3%) women, intraoperative uterine perforation occurred. Complete follow-up was available for 49/64 (76%) patients. Mean follow-up time was 68.6+/-5.2 months. The overall pregnancy rate after hysteroscopic septoplasty was 69% (34/49). The overall life birth rate (LBR) was 49% (24/49). The mean time interval between surgery and the first life birth was 35.8+/-22.5 months. Including our own data, we identified 18 studies investigating the effect of septoplasty on reproductive outcome in 1501 women. A pooled analysis demonstrated that hysteroscopic septoplasty resulted in an overall pregnancy rate of 60% (892/1501) and a LBR of 45% (686/1501). The overall rate of intra- and postoperative complications was 1.7% (23/1324) and the overall rate of re-hysteroscopy was 6% (79/1324). CONCLUSIONS: In women with septate uterus and a history of infertility, hysteroscopic septoplasty is a safe and effective procedure resulting in a pregnancy rate of 60% and a LBR of 45%.

OCT-4 expression in follicular and luteal phase endometrium: a pilot study.

BACKGROUND: The stem cell marker Octamer-4 (OCT-4) is expressed in human endometrium. Menstrual cycle-dependency of OCT-4 expression has not been investigated to date. METHODS: In a prospective, single center cohort study of 98 women undergoing hysteroscopy during the follicular (n = 49) and the luteal (n = 40) phases of the menstrual cycle, we obtained endometrial samples. Specimens were investigated for OCT-4 expression on the mRNA and protein levels using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Expression of OCT-4 was correlated to menstrual cycle phase. RESULTS: Of 89 women sampled, 49 were in the follicular phase and 40 were in the luteal phase. OCT-4 mRNA was detected in all samples. Increased OCT-4 mRNA levels in the follicular and luteal phases was found in 35/49 (71%) and 27/40 (68%) of women, respectively (p = 0.9). Increased expression of OCT-4 protein was identified in 56/89 (63%) samples. Increased expression of OCT-4 protein in the follicular and luteal phases was found in 33/49 (67%) and 23/40 (58%) of women, respectively (p = 0.5). CONCLUSIONS: On the mRNA and protein levels, OCT-4 is not differentially expressed during the menstrual cycle. Endometrial OCT-4 is not involved in or modulated by hormone-induced cyclical changes of the endometrium.

Administration of betaHCG leads to dose-dependent changes of gene expression signature of endometriotic stromal cells.

Preliminary studies have shown that systemic beta-human chorionic gonadotrophin (betaHCG) therapy alleviates endometriosis-related chronic pelvic pain. The underlying mechanism, however, is completely unknown. This study has investigated the dose-dependent alterations in the overall gene expression profile of endometriosis-derived stromal cells under increasing concentrations of betaHCG by using the Affymetrix GeneChip U133 Set. It has been previously shown that betaHCG concentrations of 0.1U/ml and higher lead to a significant and dose-dependent increase in the expression of 68 genes. This study reports on a cluster analysis which identified three clusters of genes with a comparable expression pattern in response to increasing concentrations of betaHCG. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix remodelling, apoptosis and inflammation. Stromal monocultures from eight patients, treated with and without 50U/ml of betaHCG, were then incubated and real-time polymerase chain reaction for the highly up-regulated genes PAI2, DUSP6, PLAU and MMP1 performed in order to validate the cDNA array findings in patients with endometriosis. Taken together, this study shows that betaHCG induces dose-dependent characteristic response clusters in the gene expression profile of stromal cells obtained from endometriotic lesions which could explain the differential biological responses of betaHCG in endometriosis.

Combined hysterectomy/salpingo-oophorectomy and mastectomy is a safe and valuable procedure for female-to-male transsexuals.

INTRODUCTION: Sex reassignment surgery is an important step for transsexuals, since it is known to help the patients to live more easily in their gender role and to significantly increase quality of life. AIMS: To critically evaluate our experience with the combined procedure of hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy for female-to-male (FtM) transsexual patients. METHODS: Thirty-two FtM transsexuals who underwent hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy in one single operative setting. MAIN OUTCOME MEASURES: Operating time and complications, both intra-and postoperatively. RESULTS: Patients were 30.0 ± 5.8 years of age, with a body mass index of 24.8 ± 3.5 kg/m(2). The majority of patients underwent hysterectomy and bilateral salpingo-oophorectomy by laparoscopy (31/32, 96.9%). The median operating time was 222.5 minutes (inter-quartile range [IQR] 190-270 minutes). The median postoperative stay was eight days (IQR, 7-9 days). Postoperative adverse events were found in five patients (15.6%), including breast hematomas as the most frequent complication (4/32, 12.5%). In one patient (1/32; 3.1%), conversion from laparoscopy to laparotomy was necessary, which was considered an adverse event. None of our patients required reoperation or readmission to the hospital. CONCLUSION: Combined hysterectomy/salpingo-oophorectomy, and bilateral mastectomy in a single operating session seems a safe, feasible, and valuable procedure for FtM transsexuals.

Ex-vivo expanded umbilical cord blood stem cells retain capacity for myocardial regeneration.

BACKGROUND: Umbilical cord blood (UCB) is a source of human hematopoietic precursor cells (HPCs), a stem cell (SC) type that has been used in several trials for myocardial repair. A certain minimal number of cells is required for measurable regeneration and a major challenge of SC-based regenerative therapy constitutes ex-vivo expansion of the primitive cell compartment. The aim of this study was to investigate the ex-vivo expansion potential of UCB-derived HPCs and the ability of these expanded cells to migrate to the site of damage and improve ventricular function in a rodent model of myocardial infarction (MI). METHODS AND RESULTS: UCB-derived HPCs, defined by coexpression of CD133 and CD34, were expanded using various cytokine combinations. MI was induced by left anterior descending artery ligation in nude rats. Cells were injected intravenously 2 days after infarction. The combination of SC factor, thrombopoietin, flt3-ligand and interleukin-6 was found to be the most effective for inducing proliferation of HPCs. The migratory capacity of expanded HPCs was similar to that of non-expanded HPCs and improvement of ejection fraction was significant in both groups, with a relative increase of >60%. CONCLUSIONS: UCB-derived HPCs can be reproducibly expanded ex-vivo and retain their potential to improve cardiac function post-MI. (Circ J 2010; 74: 188 - 194).

17beta-estradiol acting as an electron mediator: experiments in vitro.

BACKGROUND: The present work reports on the effect of oxidizing (OH, O(2)(*-)) and reducing free radicals (e(-)(aq), H) on 17beta-estradiol (17betaE2) in respect to breast cancer initiation. The objectives of the study were based on the following premise: the ability of 17betaE2 to emit electrons (e(-)(aq)) as well as to transfer them to other biological systems. Thereby, the resulting transient hormone products are leading to the formation of metabolites, some of which may initiate the neoplastic process. The present work considers the effect of the simultaneously generated oxidizing and reducing free radicals on the carcinogenic properties of the 17betaE2 metabolites. MATERIALS AND METHODS: Water-soluble 17betaE2 with incorporated 2-hydroxypropyl-beta-cyclodextrin (HBC) in various aqueous media (pH ~7.4), saturated with air, N(2)O or argon, as well as HBC alone, were exposed to the action of free radicals produced by gamma-ray. Escherichia coli bacteria (AB 1157) were used as a model for living systems. RESULTS: From the survival curves obtained under different conditions, the derived DeltaD(37) values (representing the radiation dose at which N/N(0)=0.37; N/N(0) ratio: N(0)=starting number of colonies, N=number after irradiation treatment) illustrate that 17betaE2 as well as HBC act as very powerful scavengers of OH and O(2)(*-) radicals. On the other hand, 17betaE2 and HBC intermediates resulting from attack of the reducing species (e(-)(aq), H) have strong anticancer properties. CONCLUSION: It is stated that DeltaD(37) values strongly depend on the reactivity of the individual free radicals. Oxidizing free radicals lead to positive DeltaD(37) values, illustrating the strongly pronounced radiation protecting ability of the systems. On the contrary, the primary reducing free radicals result in negative DeltaD(37) values, indicating anticancer effect.

Mutual interaction of 17beta-estradiol and progesterone: electron emission. Free radical effect studied by experiments in vitro.

BACKGROUND: Based on the different behaviour of 17beta-estradiol (17betaE(2)) and progesterone (PRG), it was of interest to investigate the interaction of both hormones in respect of their electron emission and cytotoxicity by experiments in vitro. MATERIALS AND METHODS: The studies include determination of emitted electrons (e(-)(aq)) by the individual hormones as well as by their mixtures, all complexed with cyclodextrin (HBC). Experiments in vitro (Escherichia coli bacteria) were performed for a better understanding of the mechanisms involved. Survival ratios, DeltaD(37)(Gy), were calculated. RESULTS: Aqueous HBC as well as 17betaE(2) and PRG, individually as well as in mixtures, are able to emit e(-)(aq). The resulting transients can lead to the formation of metabolites, some of which can initiate cancer. It was established that both hormones, 17betaE(2) and PRG, interact in respect to their electron emission property. In the frame of experiments in vitro, it was found that oxidizing radicals (OH, O(2)(-)) lead to negative DeltaD(37)(Gy) values, indicating cytostatic properties. On the other hand, the primary reducing radicals (e(-)(aq), H) lead to positive DeltaD(37)(Gy) values, indicating a radical-scavenging effect. CONCLUSION: The main outcome of this work is that PRG in combination with 17betaE(2) can strongly reduce the number of carcinogenic 17betaE(2)-metabolites. This fact offers a new pathway for application of hormones in medical treatment of patients.

Ovarian tissue cryopreservation for non-malignant indications.

BACKGROUND: Ovarian tissue cryopreservation (OTC) is not restricted to patients suffering from malignancies. Benign haematopoietic diseases such as autoimmune diseases and others have been mentioned to be feasible indications. The aim of our study was to demonstrate that surgery for OTC is a safe procedure for fertility preservation in patients with non-malignant diseases. METHODS: In a retrospective cohort study intra- and postoperative courses were evaluated. Histological examination of one random ovarian cortical slice was performed to determine the presence of primordial follicles. Immediately after the excision, microbiological culture techniques from swabs were taken from all slices. RESULTS: Seven of 85 patients (8.2%) have undergone surgery for OTC for non-malignant indications. All patients had an uncomplicated intraoperative course. A median number of 12 cortical stripes were excised and cryopreserved (range 7-17). Only for one patient an adverse event was found which was not related to laparoscopy for OTC. All patients having undergone routine laparoscopy for OTC only could be released from hospital on the first postoperative day. Selective microbiological tests showed negative results in all cases. Histological examinations revealed intact ovarian tissue with primordial follicles in 6/7 patients. CONCLUSION: Whether surgery for OTC in patients with non-malignant indications is feasible from an ethical point of view remains open. However, laparoscopy for ovarian tissue harvesting is a safe procedure for patients undergoing cytotoxic treatment for benign diseases.

Luteinizing hormone and androstendione are independent predictors of ovulation after laparoscopic ovarian drilling: a retrospective cohort study.

BACKGROUND: Our objective was to investigate luteinizing hormone, follicle-stimulating hormone, testosterone, and androstenedione as predicitve markers for ovulation after laparoscopic ovarian drilling. METHODS: We retrospectively analyzed 100 clompihen-resistant patients with the polycystic ovary syndrome who underwent laparoscopic ovarian drilling at our department. The main outcome measure was spontaneous postoperative ovulation within three months after laparoscopic ovarian drilling. In order to predict spontaneous ovulation, we tested the following parameters by use of a univariate followed by a multivariate regression model: Preoperative serum levels of LH, FSH, testosterone, and androstenedione as well as patients' age and body mass index. In addition, we focused on pregnancy and life birth rates. RESULTS: Spontaneous ovulation was documented in 71/100 patients (71.0%). In a univariate and multivariate analysis, luteinizing hormone (OR 1.58, 95%CI: 1.30-1.92) and androstenedione (OR 3.03, 95%CI: 1.20-7.67), but not follicle-stimulating hormone and testosterone were independent predictors of ovulation. Using a cut-off for luteinizing hormone and androstenedione of 12.1 IU/l and 3.26 ng/ml, respectively, spontaneous ovulation was observed in 63/70 (90.0%) and 36/42 patients (85.7%) with elevated and in 8/30 (26.7%) and 35/58 (60.3%) patients with low luteinizing hormone and androstenedione levels, respectively. The sensitivity, specificity, positive and negative predictive values for luteinizing hormone and androstendione as predictors of spontaneous ovulation after ovarian drilling were 88.7% (95%CI: 79.0-95.0%), 75.9% (95%CI: 56.5-89.7%), 90.0% (95%CI: 80.5-95.8%), and 73.3% (95%CI: 54.1-87.7%) for luteinizing hormone, and 50.7% (95%CI: 38.6-62.8%), 79.3% (95%CI: 60.3-92.0%), 85.7% (95%CI: 71.5-94.6%), and 39.7% (95%CI: 27.0-53.4%) for androstenedione, respectively. Complete one-year follow-up was available for 74/100 patients (74%). We observed a one-year pregnancy rate and a resulting life-birth rate of 61% and 51%, respectively. CONCLUSIONS: Luteinizing hormone and androstenedione prior to laparoscopic ovarian drilling are independent predictors of spontaneous ovulation within three months of surgery. We suggest to preferentially performing laparoscopic ovarian drilling in patients with high luteinizing hormone and androstenedione levels.

Venous thrombembolism, thrombophilic defects, combined oral contraception and anticoagulation.

BACKGROUND: Several genetic polymorphisms increase the risk for venous thrombembolism (VTE). In particular, combined oral contraceptives (COCs) are known to enhance the risk for VTE and are therefore contraindicated. CASE: We present here the case of a patient with protein S deficiency, who has used COCs together with anticoagulatory therapy (Phenprocoumon) after suffering from deep venous thromboses for 4 years. At the time of her first consultation at our clinic, the ultrasound examination showed a complete involution of her venous thrombosis. CONCLUSION: COCs can be used in patients with thrombogenic mutations and anticoagulatory therapy in individual cases.

Progesterone for recurrent miscarriage: truth and deceptions.

Recurrent miscarriage is known to affect 0.5-2% of pregnant women, and the standard investigative protocol fails to identify a specific cause in 50% of cases. Progesterone, a key hormone in pregnancy maintenance, has been used to support early pregnancy for decades. A growing body of considerable evidence indicates that in addition to women with luteal phase defects, women with idiopathic recurrent miscarriage may benefit from progestogen treatment, as progesterone has been shown to be an essential immunomodulatory agent in early pregnancy. It plays a critical role in the expression, modulation and inhibition of various growth factors, cytokines, cell adhesion molecules and decidual proteins. Some studies have revealed a remarkable improvement in pregnancy outcome after progestogen supplementation in women suffering from recurrent miscarriage. As most studies on this topic are of unsufficient statistical power, further research on the efficacy of progestogen treatment in affected women is required.

Photo-induced electron emission from 17beta-estradiol and progesterone and possible biological consequences.

It was established for the first time, that the sexual hormones 17beta-estradiol (17betaE2) and progesterone (PRG) are able to emit electrons from their excited single state in water-ethanol mixtures. The yield of the "solvated electrons" (e(s)(-)) depends on the substrate concentration, the ratio of water-alcohol-mixtures and the temperature. The e(s)(-) yield obtained from 17betaE2 is by two orders of magnitude higher than this of PRG. The possible relationship of the resulting hormone transients from 17betaE2 leading via specific metabolites to breast cancer is discussed.

Effect of an oral contraceptive with chlormadinone acetate on depressive mood : analysis of data from four observational studies.

BACKGROUND AND OBJECTIVE: Many women of reproductive age experience depressive mood symptoms such as sudden mood swings, irritability, nervousness, excitability and anxiety. Although not defined as a disease, these disturbing mental symptoms are associated with a considerable decrease in quality of life. Molecular pharmacology research over the last 20 years has shown that endogenous steroid hormones may interact with the CNS. Some of these hormones, i.e. the sex hormone progesterone and its 3alpha-reduced metabolites allopregnanolone (3alpha,5alpha-tetrahydroprogesterone) and epipregnanolone (3alpha,5beta-tetrahydroprogesterone, eltanolone), influence mood-balancing and anxiolytic effects via the gamma-aminobutyric acid receptor A (GABA(A)), a major inhibiting receptor of the CNS. Activation of GABA(A) receptor results in mood balancing, anxiolytic, antiepileptic and sedative actions. When oral contraception is considered, it should be taken into account that the various synthetic progestogens used may differ in their influence on mental state. For instance, there is strong clinical evidence of mood-balancing effects for the progesterone derivative chlormadinone acetate (CMA). The aim of these studies was to describe the clinical effects of CMA in combination with ethinylestradiol on depressive mood symptoms. METHODS: Data from four prospective, non-interventional observational studies involving nearly 50 000 women were analysed. The studies documented use of four, six and 12 treatment cycles of the 28-day conventional regimen, as well as providing data on extended cycle regimens. The women in these studies were prescribed CMA 2 mg and ethinylestradiol (EE) 0.03 mg according to gynaecologists' usual practice. RESULTS: Clinical data from the studies confirmed that intake of CMA 2 mg and EE 0.03 mg promotes emotional well-being and reduces mood swings. Improvement in depressive mood was documented after four, six and 12 treatment cycles of the conventional intake regimen as well as with an extended-cycle regimen of CMA/EE. CONCLUSION: CMA 2 mg combined with EE 0.3 mg improves symptoms of depressive mood. The high structural congruence between the endogenous GABA(A) modulator epipregnanolone and the CMA metabolite M-V suggests a direct GABAergic, mood stabilizing function of CMA. We propose a theoretical concept - the CMA-GABA(A) model - that could explain the positive psychotropic effect of CMA.