Lack of evidence that progesterone in ovulatory cycles causes breast cancer.

A recent Perspective article asserted that progesterone secretion during ovulatory cycles is the cause of breast cancer. However, we challenge most of the evidence developed in this publication. First, there is a lack of evidence that progesterone is mutagenic for breast cells. Cause of a cancer should mean initiation by mutation, as opposed to promotion. Second, subclinical ovulatory disturbances occur rather frequently in normal-length menstrual cycles. Third, the authors attribute a potential carcinogenic effect to progesterone secreted during menstrual cycles but not to progesterone during pregnancy. They did not discuss breast cancer evidence from progesterone/progestin therapeutics. They argue that in genetic primary amenorrhea, a hypothetic lower risk of breast cancer could be due to the lack of progesterone, despite the progesterone/progestin in hormone replacements these women receive. Fourth, they advocate a regulatory effect of progesterone on several genes potentially involved in cancer genesis. In particular, they attribute a lower risk of breast cancer in women with Mayer-Rokitansky-Küster-Hauser syndrome to a defect in the progesterone-stimulated Wnt4 gene. However, this defect is only present in a small subset. Thus, the postulated progesterone breast cancer risk is unconvincing, which we discuss point by point in this commentary.

Integrated morphologic and molecular analysis of Trichomonas vaginalis, Mycoplasma hominis, and human papillomavirus using cytologic smear preparations.

Pathogenic microbes may colonize the female genital tract via sexual transmission and cause health issues like inflammation or malignancy, summarized as sexually transmitted disease (STD). A major representative of such pathogens is Trichomonas vaginalis (T.v.), whose role in the etiology of cervical cancer remains elusive. Traditional morphologic screening of cervical smears is able to detect T.v., although its identification may be complicated by look-alikes such as degenerated granulocytes and basal cells. In addition, the parasite's endosymbiont Mycoplasma hominis (M.h.) cannot be detected in the Pap test. This investigation was aimed at designing a PCR-based method to detect specific pathogenic germs by using cervical cytology slides to overcome morphologic uncertainty and increase diagnostic accuracy. To test our molecular screening method on T.v., M.h., and HPV in archival smears, we elaborated a multiplex PCR approach based on microdissection. This assay was applied to a minute quantity of starting material which harbored or was suspected to harbor T.v.; the resulting isolated DNA was used for subsequent molecular analyses of T.v., M.h., and HPV. We clarified the diagnosis of genital T.v. infection in 88 and 1.8% of morphologically suspicious and T.v.-negative cases, respectively. We also revealed a tendency of M.h. co-infection in high-risk HPV cases. In conclusion, a microdissection-based approach to detect pathogenic microbes such as T.v., HPV, and M.h. is a molecular tool easy to implement and may help to better understand the interactivity of these germs with respect to pathogenesis.

Hormonal Smartphone Diagnostics.

Mobile point-of-care diagnostics are paramount for the provision of healthcare. Hormonal diagnostics are powerful tools to monitor timely changes in human physiology. Hormone concentrations in serum directly correlate with urine excretions with minor time delays. Therefore, rapid tests for hormones in urine have been widely used for decades as means of early diagnostics, particularly in lateral flow immunoassay formats. However, the challenge of reading and interpreting these binary tests remains. Here we present a method for utilizing mobile technologies to quantitatively read and interpret hormonal test strips. The method demonstrates the detection of a urinary by-product of progesterone, pregnanediol glucuronide (PdG), and its relation to ovulation and the fertility cycle.

Estrogen-progestin therapy causes a greater increase in spinal bone mineral density than estrogen therapy - a systematic review and meta-analysis of controlled trials with direct randomization.

OBJECTIVE: To assess whether progesterone (P4) or osteoblast P4 receptor-acting progestin (P) contributed to estrogen (E) therapy-related increased areal bone mineral density (BMD) in randomized controlled trials (RCT) with direct randomization to estrogen (ET) or estrogen-progestin (EPT) therapy. METHODS: Systematic literature searches in biomedical databases identified RCT with direct randomization and parallel estrogen doses that measured spinal BMD change/year. Cyclic P4/P was included in this random effects meta-analysis only if for ≥ half the number of E-days. RESULTS: Searches yielded 155 publications; five met inclusion criteria providing eight dose-parallel ET-EPT comparisons in 1058 women. Women averaged mid-50 years, ⟨five years into menopause and took conjugated equine E daily at 0.625 mg with/without 2.5 mg medroxyprogesterone acetate (MPA). The weighted mean EPT minus ET percentage difference in spinal BMD change was +0.68%/year (95% CI 0.38, 0.97%) (P=0.00001). This result was highly heterogeneous (I²=81%) but this may reflect the small number of studies. CONCLUSION: Estrogen with an osteoblast P4R-acting progestin (EPT) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET. These data have implications for management of vasomotor symptoms and potentially for osteoporosis treatment in menopausal women.

[German ophthalmology in developing countries : Partnerships with eye clinics in developing countries - an initiative of the German Ophthalmological Society]. / Deutsche Augenheilkunde in Entwicklungsländern : Partnerschaften mit Augenkliniken in Entwicklungsländern ­ eine Initiative der Deutschen Ophthalmologischen Gesellschaft.

In 1999 the global initiative "Vision 2020 - The Right to Sight" was established by the World Health Organization (WHO), the International Agency for the Prevention of Blindness (IAPB) and several non-governmental organizations (NGOs) with the goal of reducing avoidable blindness. Based on this initiative, the working group "International Ophthalmology" of the German Ophthalmological Society (DOG), which was established in 1994, was converted into a DOG section with the same name in 2004 and represents one of the core components of the DOG; however, even before there were a number of established partnerships of German and African eye hospitals. The first cooperation of this kind was the partnership between the Department of Ophthalmology, Ludwig-Maximilians University Munich and the University of Nairobi, Kenya, which was founded in 1978. As a result of this cooperation, the Department of Ophthalmology in Nairobi has evolved into one of the major centers of ophthalmological training and ophthalmic care in East Africa. Since then a number of similar cooperation projects between several hospitals and numerous further projects (e. g. in Myanmar) have been implemented and some of these are presented in this manuscript.

C-Peptide, Baseline and Postprandial Insulin Resistance after a Carbohydrate-Rich Test Meal - Evidence for an Increased Insulin Clearance in PCOS Patients?

Introduction Known characteristics of patients with PCOS include infertility, menstrual disorders, hirsutism and also often insulin resistance. These symptoms increase with increasing body weight. In the LIPCOS study (Lifestyle Intervention for Patients with Polycystic Ovary Syndrome [PCOS]) long-term changes of the PCOS in dependence on pregnancy and parenthood were systematically assessed. In the framework of the LIPCOS study, PCOS patients were given a standardised carbohydrate-rich test meal in order to examine glucose homeostasis and insulin secretion. The results were compared with those of a eumenorrhoeic control group who all had corresponding BMI values and corresponding ages. Methods and Patients 41 PCOS patients (without diabetes) and 68 controls received a standardised carbohydrate-rich test meal (260 kcal, 62 % carbohydrates, 32 % fat, 6 % proteins) in order to generate a submaximal insulin and glucose stimulation. The values were determined at baseline and postprandial after 60, 120 and 180 minutes. In addition, the corresponding C-peptide levels were recorded. Results In the PCOS patients (n = 41), the insulin secretion test after a standardised test meal showed almost identical baseline and postprandial insulin levels when compared with those of the age- and BMI-matched eumenorrhoeic controls (n = 68). In the PCOS patients, the baseline and postprandial glucose levels were significantly elevated (92.88 ± 10.28 [PCOS] vs. 85.07 ± 9.42 mg/dL [controls]; p < 0.001) so was C-peptide (p < 0.025). Conclusions In the present study we have shown for the first time that, after consumption of a standardised test meal, PCOS patients formally exhibit a higher fasting insulin resistance than controls. In spite of the higher stimulated C-peptide levels, the insulin levels did not increase more strongly with increasing glucose levels than in controls which may be indicative of a higher insulin clearance in PCOS patients.

Premenopausal Trabecular Bone Loss is Associated with a Family History of Fragility Fracture.

INTRODUCTION: Although a fragility fracture family history (FFFH+) has repeatedly been shown to be associated with lower bone mineral density (BMD), its relationship to human BMD change is unclear. Animal research, however, documented that different purebred strains within rodent species have wide ranges in rates of bone acquisition during growth as well as in change post-ovariectomy. Our objective was to compare the rate of premenopausal spinal trabecular BMD change between women with and without a general family history of fragility fracture. PARTICIPANTS AND METHODS: Healthy premenopausal community women participated in prospective observational studies at two academic medical research centres: Vancouver, Canada (n = 66) and Munich, Germany (n = 20). The primary outcome was annual spinal BMD change, measured by quantitative computed tomography (QCT). The two studies employed similar methodologies for assessing QCT and FFFH. RESULTS: Volunteer community participants had a mean age of 36.0 (SD, 6.9) years, body mass index 22.5 (2.4) and baseline QCT of 150.2 (22.5) mg/cm3 trabecular bone. The rates of BMD change were similar in both cities: - 3.5 (5.1)/year Vancouver, - 2.0 (3.4)/year Munich (95 % CI of difference: - 3.9, 0.9). Over a third of the women (31 of the 86, 36 %) reported FFFH+. Those with and without a FFFH were similar in demographics, nutrition, exercise, menstrual cycle and luteal phase lengths and physiological measures (serum calcium, osteocalcin and estradiol). However, women with FFFH+ lost trabecular BMD more rapidly: FFFH+, - 4.9 (5.0), FFFH-, - 2.2 (4.4) mg/cm3/year (95 % CI diff - 0.7 to - 4.8, F1.83 = 7.88, p = 0.006). FFFH+ explained 7.7 % of the variance in QCT volumetric trabecular spinal bone change/year in these healthy premenopausal women. CONCLUSION: This study shows for the first time that having a history of a fragility fracture in a family member is associated with a greater rate of premenopausal spinal trabecular bone loss.

Vitamin D and Mammographic Findings.

Introduction: Pleiotropic immune-modulatory and anti-proliferative effects of vitamin D and hopes to stop cancerogenesis have led to an increased interest in possible reduction of breast cancer with higher vitamin D levels. Mammographic density is an established risk factor for breast cancer risk, and its association with serum vitamin D is complex, as recent studies have shown. Patients and Methods: In this cross-sectional study, 1103 participants were recruited in the breast diagnostic unit of the Klinikum rechts der Isar, TU Munich. A standardised questionnaire and blood samples for 25-OH-vitamin D were taken on the day of mammography. Histologic results of biopsies in suspicious mammographies were documented. Results: In the 1090 data-sets analysed, vitamin D-deficiency was common among women under 40. Highest vitamin D values were observed in participants aged 60-69 years, but average values for all age cohorts were below 20 ng/ml of vitamin D. 15.6 % of all participants had very low vitamin D values (< 10 ng/ml), 51.3 % were vitamin D-deficient (10-19 ng/ml) and only 5.7 % were above 30 ng/ml, i.e. showed sufficient vitamin D. Patients with malignant results had vitamin D < 10 ng/ml more often (16.9 %; p = 0.61), and only 3.4 % in this group had sufficient vitamin D supply (> 30 ng/ml). There were no significant differences in vitamin D-levels between density groups according to the American College of Radiology (ACR) criteria. Conclusion: Vitamin D values were lower than in comparable US women. Up to now, there is no direct clinical evidence for a relationship between the risk for breast cancer and a specific vitamin D value.

[International ophthalmology and travel medicine]. / Internationale Ophthalmologie und Reisemedizin.

Medical eye care in developing countries is very different from the situation in industrialized nations. In order to prevent rising numbers of blind people worldwide due to increased life expectancy and population growth, the global initiative Vision 2020 "The Right to Sight" was established in 1999. Coordinated initiatives are important as most causes of blindness are either preventable or curable (e.g. cataract surgery); however, due to a lack of resources eye care in developing countries cannot implement all necessary preventive and therapeutic measures at present. The epidemiology of causes of blindness and the situation of ophthalmic care are discussed. Because of increased mobility of people and goods (e.g. air travel and trucking), imported eye diseases are of increasing importance. The difference between travel medicine, which deals with the medical situation of travelers and international ophthalmology (i.e. diseases in tropical countries) is discussed and illustrated on the basis of several important disease patterns.

[Tropical ophthalmology : Intraocular inflammation caused by "new" infectious pathogens and travel-related infections]. / Tropenophthalmologie : Intraokulare Entzündungen bei "neuen" Infektionserregern und Reiseinfektionen.

A number of "new" (emerging) infections that can also cause inflammatory eye changes are appearing and becoming increasingly important. In the past, diseases such as chikungunya, dengue fever or West Nile virus infections were endemic in tropical regions, but are now expanding worldwide and causing significant morbidity and even mortality. "Globalization" and human migration are important factors leading to the import of these infections. Climate changes are probably even more important. Increasing temperatures provide suitable conditions for new vectors, and may lead to autochthonous transmission of infectious pathogens. Diagnosis of these diseases requires not only careful assessment of medical and travel history, but also the application of specific laboratory diagnostic tests. A broad spectrum of ocular involvement has been reported, with frequent posterior segment involvement. Emerging infections should therefore be considered in the differential diagnosis of retinitis, chorioretinitis, retinal vasculitis and optic neuropathy in a patient living in or traveling back from an endemic area. Since these infections are often vector (insect) borne and effective treatments are almost uniformly lacking, prevention is at least as important as prompt diagnosis and initiation of supportive care. Here, we focus on Chikungunya, Dengue fever, Ebola fever, the West Nile virus and Rickettsioses, which frequently demonstrate ocular involvement.

[Staying and working at home or considering migrating: Survey-based study of African ophthalmologists]. / Arbeiten im Heimatland oder an Auswandern Denken: Fragebogenbasierte Studie mit afrikanischen Augenärzten.

BACKGROUND: The shortage of ophthalmologists is a major obstacle in the struggle of fighting preventable blindness in sub-Saharan Africa. However, to date reasons affecting migration of ophthalmologists have not been completely understood. OBJECTIVES: Evaluation of reasons reported by ophthalmologists for staying in their current work setting/country, of potential reasons for migration as well as of effects of German-African partnerships. MATERIAL AND METHODS: In the years 2009-2011 and 2013 participants of continuous medical education courses in Ethiopia, Cameroon and Kenya were interviewed using a standardized questionnaire. RESULTS: A total of 106 ophthalmologists participated in this survey. In the years 2009/2010 participants were mainly board certified ophthalmologists, while the 2011/2013 surveys were answered mainly by residents. The main reasons for staying in their current region/country were good working conditions, commitment to help/patriotism, possibility of further training, good income and familial ties. Professional development elsewhere and better income abroad were named as the main reasons for considering migration followed by better technical equipment elsewhere and insecurity in the home country. CONCLUSION: Good working conditions and the possibility of further training were named as the top reasons for staying in the current region/country apart from commitment to help and familial ties. Therefore, international cooperation programs aiming at improving training of ophthalmologists and establishing an ophthalmic infrastructure may have a role in promoting ophthalmic care in Africa.

Do Pregnancy and Parenthood Affect the Course of PCO Syndrome? Initial Results from the LIPCOS Study (Lifestyle Intervention for Patients with Polycystic Ovary Syndrome [PCOS]).

Introduction: The impact of pregnancy and parenthood on the long-term course of PCOS (polycystic ovary syndrome is still not known. The LIPCOS study (Lifestyle Intervention for Patients with Polycystic Ovary Syndrome [PCOS] - using the example of pregnancy and parenthood) systematically investigates long-term changes in PCOS symptoms. Method and Patients: The LIPCOS pilot study sent out a questionnaire to 403 patients who had presented with oligomenorrhea between 1991 and 2002. The prospective LIPCOS main study systematically investigated 64 women using structured interviews about lifestyle changes in the last 10 years, created a detailed hormone profile of these women and carried out vaginal ultrasound to calculate ovarian score. Results: Ovarian volume and ovarian score were not significantly lower for women with children (n = 25) compared to women with PCOS who had not had children (n = 39; p = 0.226). More women with children than women who did not have children currently reported a regular daily lifestyle, and the difference was statistically significant (92 % [n = 23/25] vs. 61.5 % [n = 24/39]; p = 0.009). Ten years ago or before the birth of their first child, respectively, no such difference was found between both groups (52 vs. 51.3 %). Over the last 10 years, women with children were more likely to have shorter cycles compared to women without children (p = 0.441). 88 % of women with children compared to 69.2 % of women without children reported that currently they had a "healthy diet" (p = 0.130). Serum testosterone levels were slightly lower for women with children (67.6 % of the upper limits of normal ranges) compared to women without children (80 % of the upper limits of normal ranges), but because of the small subgroup sizes the difference was not statistically significant (p = 0.106). Conclusion: The LIPCOS study shows for the first time that pregnancy and parenthood may have an impact on the long-term course of PCOS. Women with children reported shorter cycles and had lower testosterone levels compared to women without children.

Non-reproductive Effects of Anovulation: Bone Metabolism in the Luteal Phase of Premenopausal Women Differs between Ovulatory and Anovulatory Cycles.

Introduction: Several authors have linked subclinical ovulatory disturbances in normal length menstrual cycles to premenopausal fracture risk and bone changes. This study systematically examined the influence of ovulation and anovulation on the bone metabolism of premenopausal women. Participants and Methods: In 176 cycles in healthy premenopausal women, FSH, 17ß-estradiol (E2) and progesterone (P4) as well as bone alkalic phosphatase (BAP), pyridinoline (PYD) and C-terminal crosslinks (CTX) were measured during the follicular and during the luteal phase. The probability and timing of ovulation was self-assessed by a monitoring device. In addition, bone density of the lumbar spine was measured by quantitative computed tomography (QCT) at baseline and at the end of the study. Analysis was restricted to blood samples taken more than three days before the following menstruation. Results: 118 cycles out of the 176 collected cycles were complete with blood samples taken within the correct time interval. Of these, 56.8 % were ovulatory by two criteria (ovulation symbol shown on the monitor display and LP progesterone > 6 ng/ml), 33.1 % were possibly ovulatory by one criterion (ovulation symbol shown on the monitor display or LP progesterone > 6 ng/ml), and 10.2 % were anovulatory by both criteria). Ovulation in the previous cycle and in the same cycle did not significantly influence the mean absolute concentrations of the bone markers. However, bone formation (BAP) was higher in the luteal phase of ovulatory cycles than in anovulatory cycles (n. s.) and the relative changes within one cycle were significantly different for bone resorption (CTX) during ovulatory vs. anovulatory cycles (p < 0.01). In 68 pairs of cycles following each other directly, both ovulation in the previous cycle and ovulation in the present cycle influenced CTX, but not the differences of other bone markers. Conclusion: Ovulatory cycles reduce bone resorption in their luteal phase and that of the following cycle. The interaction between ovulation and bone metabolism is complex. Since anovulation may occur in low estrogen states such as pre-anorexic dietary restraint, as well as with high estrogenic circumstances e.g. from functional perimenopausal ovarian cysts, the association with bone changes has been variable in the literature. Accumulating physiological and clinical evidence however point towards a role for ovulation in enhancing bone formation and limiting bone resorption.

Bone loss in premenopausal, perimenopausal and postmenopausal women: results of a prospective observational study over 9 years.

INTRODUCTION: Few longitudinal data about rates of bone loss in women in midlife exist. Fewer still with their reproductive states having been carefully assessed and sequentially followed-up. METHODS: Complete data from 50 women younger than 60 years (mean age at baseline 48.3 ± 5.4 years) were prospectively collected over 9 years. This was done by standardized interviews, measurement of endocrinological parameters as well as bone markers and repeated bone mineral density (BMD) measurements using quantitative computer tomography (QCT). Women were classified in three groups according to their reproductive characteristics over 9 years. RESULTS: Significant BMD loss was found in women going through the menopausal transition. In perimenopause, there was a correlation (multiple regression results, r = -0.396 and r = -0.527) between accelerated bone density loss and increased gonadotropin levels (follicle stimulating hormone, luteinizing hormone). Although significantly higher levels of bone markers (osteocalcin, bone-specific alkaline phosphatase, c-terminal telopeptide cross-linked collagen type I) were measured in postmenopause, the greatest increase in these markers was seen during the menopausal transition. No individual marker's increase, however, was predictive for perimenopausal bone density loss. The major risk factors for rapid bone loss were a lower initial body weight (< 57 kg), a body mass index < 20 kg/m(2) as well as a positive family history of fragility fractures. CONCLUSIONS: Women in the menopausal transition lose trabecular bone at a rapid rate despite intermittently high and usually normal estrogen levels. This is the only prospective study to date that documents trabecular bone changes in women through the entire perimenopause, which may last up to 10 years.

Progesterone and bone: a closer link than previously realized.

Decreasing rates of ovulation, hormonal changes, and increasing bone loss pre-date menopause by several years. Data suggest that, in addition to estradiol, progesterone may play a significant role in the interrelationship between the ovaries and the skeleton in women. Indeed, the differentiation of human osteoblasts from perimenopausal women has been shown to be dose-dependent on progesterone at physiological concentrations. Data from a pilot study in perimenopasual women also suggested that higher progesterone levels, as seen in the luteal phase of ovulatory cycles, may be associated with more bone formation and with slightly less bone resorption than anovulatory cycles in which progesterone levels are low (< 5.8 ng/ml). These data led to the initiation of a large, prospective, 2-year observational study in perimenopausal women (the PEKNO study). Interim data from the PEKNO study indicate that a decrease in ovulation correlated with an increase in the loss of bone mineral density (BMD). A meta-analysis estimated a BMD increase of 0.5% per year in women with normal ovulation, and a BMD decrease of 0.7% per year in young women with ovulatory disturbances (anovulation or short luteal phase). A meta-analysis in postmenopausal women demonstrated a 1.3% increase per year in BMD when receiving hormone replacement therapy with unopposed estrogens, and a further 0.4% increase in BMD in women receiving estrogens plus progestogens. The role of progesterone in bone metabolism in perimenopausal women who are estrogen-replete requires further study.

[Intravascular ultrasound for recognition of atherosclerotic plaques and plaque composition. Current state of the diagnostic value]. / Intravaskulärer Ultraschall zur Erkennung atherosklerotischer Plaques und der Plaquekomposition. Aktueller Stand der diagnostischen Wertigkeit.

Coronary atherosclerosis including acute coronary syndrome (ACS) is the leading cause of death in the western world and in the majority of patients is caused by plaque rupture in flow-limiting and non-flow-limiting angiographically intermediate stenoses. Histopathologic analyses have shown the relationship of plaque composition to acute clinical events and therefore to the vulnerability of coronary lesions. Knowledge of remodeling processes of the coronary artery has focused interest on non-flow-limiting lesions of the coronary tree. Intravascular ultrasound (IVUS) can demonstrate discrepancies between the extent of coronary atherosclerosis and angiographic imaging by in vivo plaque imaging. In addition the spectral analysis of IVUS-derived radiofrequency (RF) data enables more precise analysis of the plaque composition and plaque type.As IVUS is best able to assess stent underexpansion and malapposition the guidance of catheter-based coronary interventions plays a major role in angiographically unclear lesions even in the drug-eluting stent era. In the field of percutaneous coronary interventions (PCI) IVUS can influence the therapy and therefore optimize the stratification of patients.In terms of secondary prevention it is of great clinical importance to detect progression of coronary artery disease and moreover to predict coronary lesions with significant progression up to ACS. Coronary angiography and clinical parameters are poor surrogates to predict future events in a broad cohort of patients after PCI. In addition non-invasive imaging fails to identify coronary plaques with potential rupture and subsequent ACS. This highlights the need to identify potentially high risk lesions. However, prospective studies with IVUS-RF imaging to detect lesions that are considered to be prone to rupture showed no evidence for catheter-based invasive treatment of a non-flow-limiting high risk plaque.In the future the integrated combination of multiple technologies (e.g. IVUS-RF and optical coherence tomography) can further improve the accuracy of the analysis of high risk lesions.

Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (p<0.001). HRT in postmenopausal patients was associated with longer time to progression (TTP) (HR 0.81, 95%CI 0.55-1.19, p=0.28) and overall survival (OS) (HR 0.68, 95%CI 0.45-1.02, p=0.059). Perimenopausal HRT users showed shorter TTP and OS (HR 1.99, 95%CI 0.57-6.91, p=0.28 and HR 4.59, 95%CI 0.91-23.25, p=0.06 respectively). Higher BMI was significantly associated with poorer prognosis in perimenopausal women only (TTP: HR=1.16; OS: HR=1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.

Clinical management of clopidogrel inefficiency by point of care platelet function testing and individual adjustment of anti-platelet therapy--initial experiences.

Insufficient inhibition of ADP dependent platelet aggregation by clopidogrel is associated with an increased risk for adverse coronary events, such as stent thrombosis, after percutaneous coronary intervention. Here, we describe an approach to the clinical management of patients with insufficient inhibition of ADP dependent platelet aggregation by clopidogrel involving dose adjustment or switching of the thienoyridine. We put special emphasize on a patient who experienced recurrent acute myocardial infarction due to stent thrombosis associated with severe clopidogrel non response following elective coronary drug eluting stent implantation. In this patient, an inadequate clopidogrel effect at maintenance doses was confirmed by repeated platelet function assessment with a multiple electrode impedance point of care platelet function test. Subsequent dose adjustments still did not result in sufficient inhibition of ADP dependent platelet aggregation. Only after switching to the then shortly available new thienopyridine prasugrel could a sufficient platelet inhibition be obtained. However, our data from further patients show that although this may overcome inadequate clopidogrel efficiency in many cases, even under prasugrel suboptimal platelet inhibition may occur.