The role of follicular anti-Mullerian hormone in women undergoing IVF/ICSI with regard to size, oocyte presence, sociodemographic parameters, treatment variables, and other hormones and vitamins.

AIMS: The aim of this study was to evaluate the relationship between follicular anti-Mullerian hormone (fAMH) regarding follicle size, the presence of an oocyte, sociodemographic parameters, and other hormones and vitamins in follicular fluid. MATERIALS AND METHODS: This prospective exploratory cohort study included 376 follicles from 61 women undergoing IVF/ICSI cycles. The size of each follicle was measured individually, and they were divided into a large and a small group according to their size. The presence of oocytes was detected on the day of oocyte retrieval. Sociodemographic factors were documented during the course of preliminary testing. Then, other parameters of patients' serum and follicular fluid were measured. RESULTS: Small follicles contained a significantly higher concentration of fAMH than large ones did. We showed that the presence of an oocyte in a follicle is associated with a significantly higher fAMH level than in those without one (p < .001). There exists a significant but weak correlation between fAMH and the sociodemographic parameter of patients' age (r = -0.11, p < .001). We did not find a correlation with the patients' BMI (r = 0.03, p < .006). We also investigated the connections between fAMH and other parameters, such as vitamin D (r = -0.13, p < .001), LH (r = 0.35, p < .001)), and progesterone (r = -0.21, p < .001) in follicular fluid. CONCLUSIONS: This knowledge can be useful for the future development of reproductive medicine. Our results can provide an important building block for this matter.

Cost-effectiveness of social oocyte freezing in Germany: estimates based on a Markov model.

PURPOSE: Is oocyte freezing for non-medical reasons-the so-called "social freezing" (SF)-cost-effective compared to standard in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in Germany today? METHODS: We developed a model based on three strategies for women planning to postpone pregnancy. In each strategy, women actively practiced contraception until 40 then tried to conceive naturally for 1 year. If unsuccessful, women using strategy I (oocyte cryopreservation) attempted ICSI with frozen oocytes in the 2nd year, while women using strategy II (no action) further attempted natural conception. In strategy III (IVF/ICSI), women underwent 1 year of IVF/ICSI. If still unsuccessful, each strategy was followed by attempting natural conception again until 45. We used an adaptive Markov model to estimate and compare live birth rates and cost-effectiveness measures. RESULTS: For strategy I, cumulative live birth rates at age 45 generally declined with the woman's age at freezing and were between 71.4% (25 years) and 67.6% (38 years), while the cumulative success rate was 51.5% for strategy II and 60.8% for strategy III. The costs per live birth of egg freezing were age-dependent ranging between 22,418 € (30 years) and 25,590 € (38 years). The costs for strategy III were lower at 20,293 € per live birth. CONCLUSION: Based on our results, social freezing in Germany may lead to additional pregnancies among women over 40 but also to significantly higher costs, since given the current live birth success rates and pricing, social freezing does not appear to be cost-effective.

[Pregnancy after breast cancer in germany - results of a retrospective database analysis]. / Schwangerschaften nach Brustkrebs in Deutschland - Ergebnisse einer retrospektiven Datenbankanalyse.

BACKGROUND: After the establishment of the FertiPROTEKT network in 2006, an impetus for possibilities of pregnancy during and after breast cancer was introduced. Nowadays, breast cancer survivors are confronted with the question how often women become pregnant after breast cancer and whether there have been significant changes in this respect during the past 10 years. The aim of the study was, therefore, to examine the change in frequency of pregnancies after breast cancer treatment and the time from the first breast cancer diagnosis to pregnancy over one decade, i. e., the period from 2010-2012 compared to the period from 2000-2002. METHODS: The study is based on data from the IMS Disease Analyzer database, which enables access to anonymous data from registered physicians. Data from 102 gynecological practices were available for the present study. The study included women aged 20-45 with breast cancer. RESULTS: A total of 179 pregnant women were included in this study from 2000-2002 and 2010-2012. 65 pregnancies were recorded in the period from 2000-2002, 114 pregnancies from 2010-2012. The time interval from the breast cancer diagnosis to pregnancy (analysed time period was 10 years) was 896 days (SD: 690) in the period from 2000-2002 and 552 days (SD: 696) in the period from 2010-2012 (p<0.001). CONCLUSION: There was a significant increase in pregnancies within the first 2 years after the breast cancer diagnosis. These data are consistent with the intensified consultations after the introduction of the FertiPROTEKT network.

Time to pregnancy in subfertile women in German gynecological practices: analysis of a representative cohort of more than 60,000 patients.

BACKGROUND: The aim of this study was to assess the time from the first subfertility diagnosis to pregnancy (TTP) and to elucidate factors influencing TTP for patients in German gynecological practices comprising a representative sample and provide a realistic picture of the current situation in Germany. METHODS: The study collective included all women with first-time diagnoses of female infertility (ICD: N97) or unfulfilled desire for children (ICD: Z31) from the representative database (IMS Disease Analyzer). Demographic data on patients such as their age (ranges 18-25, 26-30, 31-35, 36-40 or 51-50) and information on previous pregnancies and births and concomitant diseases were collected. Data pertaining to 61,815 women from 433 gynecological practices in Germany with a first diagnosis of female infertility or an unfulfilled desire for children were analyzed. The period of data collection was between January 1, 2001 to December 31, 2012 (=144 months). The mean observation period for the patients after the first gynecological consultation was 1,420 days (=47.3 months), with a standard deviation of 879 days. RESULTS: A total of 22,744 patients became pregnant during the first year of observation (36.8%). The highest cumulative pregnancy rate was seen in women between 18 and 30 years of age (74.8%). The older the women were, the lower the cumulative pregnancy rate became (18.1% in the group of 41- to 50-year-old women). Cox regression calculations showed that the following factors considerably impaired the chances of pregnancy: age, endometriosis, diabetes mellitus, ovarian dysfunction, PCOS, previous infection of the genitourinary tract. In contrast, a couple of factors were proven to increase pregnancy rates, namely previous use of hormonal contraceptives, private insurance, previous birth, previous pregnancy and progesterone therapy (at any time). CONCLUSION: Along with information about reproductive physiology, such as decreasing fertility with maternal age, counseling in daily practice should also include individual factors influencing fertility. It is of the utmost importance to further increase public awareness of the impact of advanced female and male age on the reproductive outcome so that people can make well-informed decisions on when to start a family.

Prevalence of menopausal symptoms and their influence on adherence in women with breast cancer.

OBJECTIVES: The use of aromatase inhibitors for the adjuvant treatment of breast cancer may affect the quality of life of patients, as well as adherence to treatment. METHODS: Here we report the 2-year results of the 180 patients in the COMPAS study. This is the first randomized, controlled study reporting on menopausal symptoms under endocrine treatment with aromatase inhibitors in breast cancer patients, based on the Menopause Rating Scale. We analyzed the prevalence of menopausal symptoms as well as their associations with patient adherence. RESULTS: Baseline characteristics showed no significant differences among the control and the intervention groups. The majority of women experienced the symptoms at various severities. Overall, we found an increase in the prevalence of hot flushes, sleep disorders, bladder problems, dryness of the vagina as well as of joint and muscular discomfort between the 12- and 24-month visits. In compliant patients, all symptoms except for vaginal dryness improved between the 12- and 24-month visits while, in non-compliant women, hot flushes, irritability, dryness of the vagina as well as joint and muscular discomfort deteriorated. When comparing compliant and non-compliant patients, we found a significant difference only for anxiety (p = 0.028) in the 12-month analysis, as well as a large but non-significant difference for heart discomfort (p = 0.089) in the 24-month visit. CONCLUSIONS: Our results indicate that the majority of women treated with aromatase inhibitors are experiencing menopausal symptoms at various severities. We showed that the mean symptom values in compliant patients improve with longer therapy duration. Furthermore, anxiety correlates with better compliance, while heart discomfort may lead to therapy discontinuation.

Risk of venous thrombosis in users of hormonal contraceptives in German gynaecological practices: a patient database analysis.

PURPOSE: Recent studies showed differences in the risk of venous thrombosis between different combined hormonal contraceptives. Database studies comprising large cohorts can add relevant aspects from daily clinical practice. The purpose of this study was to evaluate different progestogen in combination with ethinylestradiol on the risk of venous thrombosis in Germany. METHODS: Computerized data from 68,168 contraceptive users in gynecological practices throughout Germany (Disease Analyzer Database) were analyzed. The adjusted odds ratios for risk of thrombosis were estimated in users of different oral contraceptive (OC) formulations relative to users of levonorgestrel-containing preparations. RESULTS: In total, 38 (0.06 %) of the 68,168 contraceptive users had a recorded diagnosis of thrombosis within 365 days after the initial prescription. The adjusted risk was 1.95 for desogestrel (95 % CI 0.52-7.29), 2.97 for dienogest (95 % CI 0.96-9.24), 1.57 for drospirenone (95 % CI 0.46-5.38), 2.54 for chlormadinone (95 % CI 0.72-9.04), and 3.24 for norgestimate (95 % CI 0.59-17.75) compared to levonorgestrel. None of those findings reached statistical significance. The maximum absolute increase versus levonorgestrel was 6 cases per 10,000 women (n.s.). CONCLUSION: The study shows the low incidence rates of thrombosis in OC users. Since there is no significant difference, this study does not confirm an increased risk but shows only a tendency for this risk of third- and fourth-generation OC versus levonorgestrel-containing products.

The prescribing of contraceptives for adolescents in German gynecologic practices in 2007 and 2011: a retrospective database analysis.

OBJECTIVE: To investigate the prescribing trend of contraceptives in adolescent girls aged 12-18 years and to compare prescribing patterns of the most frequently used contraceptives among this population in Germany in 2007 and 2011. METHODS: A retrospective cohort study was conducted to analyze contraceptive prescriptions written by gynecologists in 2007 and 2011 in Germany by using the IMS Disease Analyzer database (IMS HEALTH). All adolescent girls aged 12-18 years with at least 1 prescription of a contraceptive drug in 2007 or 2011 were identified. The prevalence of contraceptive prescriptions was calculated and the types of contraceptive substances prescribed were examined. RESULTS: A total of 21,026 teenage girls in 2007 and 18,969 in 2011 received contraceptive prescriptions. The prevalence of contraceptive prescribing rose significantly between 2007 and 2011 (P < .001). The percentage of teen girls who received prescriptions of levonorgestrel and chlormadinone pills was significantly higher in 2011 compared to 2007 (P < .001). However, the portion of contraceptive pills containing drospirenone or desogestrel significantly decreased in 2011 compared to 2007 (P < .01). CONCLUSION: There was a significant increase in contraceptive prescription usage among adolescent girls between 2007 and 2011 in Germany. However, the prescription behavior of doctors also changed; they consequently prescribed contraceptives with more evidence. Further research is needed to better understand the various factors associated with contraceptive use among this population.

Prevalence of female subfertility in German gynecological practices.

INTRODUCTION: The aim of this study was to calculate the number of women with a subfertility diagnosis in gynecological practices in Germany between 2006 and 2010 based on the data from a large epidemiological database. METHODS: All calculations are based on a representative, epidemiological database called "disease analyzer". Women with a confirmed diagnosis of female infertility (ICD 10: N97) or/and with documentation of procreative management (ICD 10: Z31) were identified. They were summarized under the term "subfertility". RESULTS: In total, data on 1,975,253 female patients with between 2006 and 2010 were included. Estimates for patients with "subfertility" compared to number of women lived in Germany (aged 18-45) was 2.44% (CI: 2.43-2.45) in 2006, 2.52% (CI: 2.51-2.53) in 2007, 2.56% (CI: 2.55-2.57) in 2008, 2.68% (CI: 2.67-2.69) in 2009 and 2.69% (CI: 2.68-2.70) in 2010. The difference was significant (p < 0.01). In total, between 2006 and 2010 an estimated 8.91% of all German women had been diagnosed "subfertile". CONCLUSION: When calculated for 5 years almost 1 out of 10 women aged 18 to 45 was counseled, investigated or treated by her gynecologist for "subfertility". This study provides reliable, representative data on a major healthcare issue in Germany.

Persistence with bisphosphonates in patients with metastatic breast cancer: a retrospective database analysis.

BACKGROUND: In women with breast cancer and bone metastasis, compliance to antiresorptive treatment is of upmost importance to ensure maximum effectiveness in clinical practice. The aim of our study was to investigate persistence with oral and intravenous bisphosphonates (BIS) in a large group of women with metastatic breast cancer and to identify the determinants of non-persistence. PATIENTS AND METHODS: We used data from the Disease Analyzer database (IMS Health, Germany), which includes 2,067 general practices and 397 gynaecological practices. From a dataset of 20 million patients, we identified 1,045 patients diagnosed between January 2001 and December 2010 with bone metastasis (ICD 10: C795) following breast cancer (ICD 10: C50) with first-time cancer-related bisphosphonate prescriptions (ATC: M03B4). Of these, 763 patients received intravenous treatment, and 280 patients received oral BIS treatment. RESULTS: After 1 year, 35.3 % of patients treated with intravenous, and 45.6 % of patients treated with oral bisphosphonates discontinued their therapy (p = 0.002). Multivariate Cox Regression analyses showed a significant increased risk of treatment discontinuation in patients using intravenous BIS (HR: 0.82) compared with oral BIS. Patients younger than 50 (HR: 1.52) were most likely to discontinue treatment compared with the reference group of women over 70. The use of other treatments, such as chemotherapy or hormone therapy, was associated with a decreased risk of treatment discontinuation. Moreover, treatment discontinuation was higher in West Germany compared with East Germany (HR: 1.65) and in patients covered under private health insurance (HR: 1.33). CONCLUSIONS: Persistence with all bisphosphonate treatments in women with breast cancer and bone metastasis is low and needs to be significantly increased to improved outcomes in clinical practice. Further research is required to understand this complex issue.

Persistence in patients with breast cancer treated with tamoxifen or aromatase inhibitors: a retrospective database analysis.

Compliance and persistence are often underestimated in breast cancer (BC) treatment. The aim of our study was to analyze the persistence with tamoxifen (TAM) and aromatase inhibitors (AI) in postmenopausal women with hormone-receptor-positive BC and to identify determinants of non-persistence. We used data of the Disease Analyzer database (IMS HEALTH, Germany) including 2,067 general practices and 397 gynecological practices. Out of a dataset of 15 million patients, we identified BC patients with a first-time TAM or AI prescriptions from October 2001 to December 2010. For persistence analyses, 12,412 women on tamoxifen, 2,796 on anastrozole, 647 on exemestane, and 1,657 on letrozole met the inclusion/exclusion criteria. Within 3 years of follow-up, the discontinuation rates increased to 52.2 % for tamoxifen, 47 % for anastrozole, 55.1 % for exemestane, and 44.3 % for letrozole treated women. A minor proportion of patients switched to a different endocrine treatment; 33 % tamoxifen, 20 % anastrozole, 22.9 % exemestane, and 23 % letrozole. The multivariate hazard ratios of the cox regression models showed that patients younger than 50 were most likely to discontinue initial therapy when compared with the reference group of women over 70 (p < 0.001). In contrast, patients treated in gynecologist practice had significantly longer persistence than patients who obtained their prescriptions in general practitioner practice (p < 0.001). In addition, the presence of the co morbidities like diabetes (p < 0.001) or depression (p < 0.002) was also associated with decreased risk of treatment discontinuation. Persistence with all endocrine treatments in women with hormone-receptor-positive BC is low and needs to be significantly increased to improved outcome in clinical practice. Further research is required to understand this complex issue.

Quality of life and health status with zoledronic acid and generic alendronate--a secondary analysis of the Rapid Onset and Sustained Efficacy (ROSE) study in postmenopausal women with low bone mass.

SUMMARY: The ROSE study compared annual infusion with zoledronic acid and weekly generic alendronate. No significant differences in quality of life or health status between treatment groups were observed. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. INTRODUCTION: A secondary analysis to evaluate quality of life, health status, adherence to alendronate and therapy preference in postmenopausal women with low bone mass who received treatment with zoledronic acid or alendronate was conducted. METHODS: Postmenopausal women with low bone mass were randomised 2:1 to receive an annual infusion of zoledronic acid or weekly oral generic alendronate in this open-label, multicentre study. Changes in quality of life and health status were assessed using questionnaires at baseline and month 12. Adherence to alendronate was assessed by the investigator and/or study personnel, and subjective therapy preference was assessed using a questionnaire at month 12. RESULTS: Patients were randomised to zoledronic acid (n = 408) and alendronate (n = 191). Overall, there were no significant differences in quality of life between zoledronic acid and alendronate. However, improvements in quality of life with zoledronic acid versus alendronate could be detected by posthoc analysis in patients with previous fractures. There were no significant differences in health status between patients receiving zoledronic acid or alendronate. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. A total of 81% of patients who had received zoledronic acid indicated that they would prefer to continue with that treatment, and 43% of the patients who received oral alendronate would like to switch to zoledronic acid. CONCLUSIONS: There were no significant differences in quality of life between patients receiving zoledronic acid or alendronate.

Rapid Onset and Sustained Efficacy (ROSE) study: results of a randomised, multicentre trial comparing the effect of zoledronic acid or alendronate on bone metabolism in postmenopausal women with low bone mass.

SUMMARY: The ROSE study compared a once-yearly intravenous dose of zoledronic acid with a once-weekly oral dose of alendronate in postmenopausal women. Once-yearly zoledronic acid showed a greater and faster reduction in the levels of two markers of bone turnover and may be an effective option for the treatment of osteoporosis. INTRODUCTION: The open-label Rapid Onset and Sustained Efficacy (ROSE) study was designed to compare a once-yearly intravenous (iv) dose of zoledronic acid with a once-weekly oral dose of alendronate with respect to markers of bone turnover in approximately 600 postmenopausal women in Germany. METHODS: Levels of N-telopeptide of collagen type I (NTx) and procollagen 1 C terminal extension peptide (P1NP) were assessed during the study. The primary objective was to assess if zoledronic acid was superior to alendronate in reducing serum NTx levels after 12 months' treatment. RESULTS: A significantly greater reduction in NTx levels from baseline to month 12 (as determined by the area under the curve) was observed in patients treated with zoledronic acid (n = 408) versus those receiving alendronate (n = 196; 0.282 ng/mL vs. 0.270 ng/mL; P = 0.012). The reduction in levels of P1NP after 1 year was also significantly greater in patients treated with zoledronic acid compared with those receiving alendronate (28.21 vs. 25.53 ng/mL; P = 0.0024). The overall incidence of adverse events was similar between groups; both treatments were generally well tolerated. Although post-dose symptoms, including the incidence of influenza-like symptoms, were higher with zoledronic acid than alendronate initially, the incidence was similar between groups from days 4-360. Gastrointestinal symptoms were more frequent with alendronate than zoledronic acid throughout the study. CONCLUSION: In this study, once-yearly iv zoledronic acid provided a greater and faster reduction in the levels of NTx and P1NP versus once-weekly oral alendronate.

GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates.

UNLABELLED: This database analysis of over 4,000 German women prescribed oral bisphosphonates between December 2004 and November 2007 showed that compliance and persistence with oral bisphosphonates in German women with osteoporosis were inadequate. INTRODUCTION: GRAND is a database analysis designed to investigate persistence and compliance with oral bisphosphonate regimens, and their association with fracture incidence, in women with osteoporosis. METHODS: Diagnostic, treatment and fracture data were obtained from the IMS Disease Analyzer patient database in Germany. Women with osteoporosis prescribed one of six specified oral bisphosphonates between December 2004 and November 2007 with no similar prescription for at least 1 year beforehand were eligible for analysis. Those treated with intravenous bisphosphonates were excluded. Persistence (prescription refill gap of ≤ 30 days or change of treatment frequency) and compliance (medication possession ratio) were measured for 2 years from therapy start. RESULTS: Data from 4,147 women were evaluable, with a median oral bisphosphonate treatment duration of 145.5 days. Persistence rates after 1 and 2 years were 27.9% and 12.9%, respectively, and 66.3% of women were compliant. As expected, persistence rates were higher when the refill gap was increased to 60 or 90 days. No significant differences in 1-year persistence between patients on weekly or monthly treatment regimens were observed (28.6% and 29.4%, respectively), although 1-year persistence with daily treatment was only 7.2%. After 24 months of therapy, compliant women had fewer fractures than non-compliant women (88.1% and 85.0% fracture-free, respectively; p = 0.0147). In multivariate Cox regression analysis, treatment compliance was the only factor that significantly decreased fracture risk (p = 0.0034). CONCLUSIONS: Compliance and persistence with oral bisphosphonates in German women with osteoporosis were inadequate. Better compliance and persistence can prevent fractures in these women.

Adherence and persistence in patients with postmenopausal osteoporosis treated with raloxifene.

OBJECTIVE: A major impediment in osteoporosis care is poor therapeutic adherence. Real-life surveys show that adherence and persistence with oral bisphosphonates decrease to 30-60% within 1 year. The aim of this study was to analyze the adherence and persistence with raloxifene in patients visiting our outpatient clinic. MATERIAL AND METHODS: A total of 342 patients were evaluated from the conventional osteoporosis practice receiving treatment with raloxifene. Patient self-reporting was combined with the medication possession ratio (MPR) assessed via prescription refill counts. In addition, persistence and other self-reported and patient file-based data were assessed. RESULTS: The final analysis comprised 300 patients with a mean age of 66.3 years (standard deviation ± 7.2 years). At 6 months 84%, at 12 months 81%, at 24 months 78% and at 36 months 77% of patients were persistent with therapy according to patients' self-reports. If MPR and self-reported data were combined, 56%, 48% and 35% of patients remained on therapy at 12, 24 and 36 months, respectively. The mean duration of therapy was 19 months with a mean MPR of 52.8%. Finally, 31.7% of all patients were classified as adherent. Significant correlation to adherence was found for tolerability and motivational factors. CONCLUSION: This study revealed that approximately half of the patients treated with raloxifene in regular clinical practice stay on therapy for the first 2 years. Furthermore, the patients do not adhere sufficiently to the recommended dosage, and reduced clinical efficacy in clinical practice is presumable. The reasons for non-adherence comprise tolerability and motivational factors but further investigation is needed.

Adherence and persistence in patients with severe osteoporosis treated with teriparatide.

INTRODUCTION: Medical intervention plays a key role in the treatment of postmenopausal osteoporosis and patients' adherence to therapy is essential for optimal clinical outcomes. While adherence in RCTs is usually around 70-90%, a previous study showed that in clinical practice only 27.8% and 46.5% of the women on oral daily vs. weekly alendronate were still on treatment after 12 months. Data on adherence to teriparatide (TPTD) treatment of severe postmenopausal osteoporosis are available from only few countries. This study assessed adherence and persistence with TPTD in Germany. MATERIAL AND METHODS: A sample of 50 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the German osteoporosis guidelines was included. Treatment was initiated 12-24 months before recruitment. Patient self report was assessed using a validated questionnaire. In addition medication possession ratio (MPR) was calculated by counting prescription refills, and therefore all physicians who were treating the patients for any disease were contacted. Patients were classified adherent at 12 months of therapy if self-reported adherence and an MPR of > or =80% were achieved. Persistence was calculated in months and analysed with a Kaplan-Meier estimate. RESULTS: Apart from a significantly lower age at menopause in the adherent group (46.1 vs. 50.0; p < 0.006) there were no significant differences in baseline demographics between adherent and non-adherent patients. After 12 months, 80% of the patients treated with TPTD were adherent, while 20% were non-adherent. A significant correlation with treatment adherence was found for self-reported medication tolerability (p < 0.001). Furthermore 79% of patients were persistent after 12 months. CONCLUSION: These results indicate that more patients seem to be adherent and persistent with TPTD than with oral treatments of postmenopausal osteoporosis. As these patients suffered from severe osteoporosis and sustained several fragility fractures, the generalisability of our retrospective study analysing a small sample is limited. The major factor that reduced adherence and persistence was tolerability. These findings are of practical relevance as numerous studies on antiresorptive therapies have shown that high adherence and persistence were needed to ensure an optimal therapeutic outcome.

Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer.

BACKGROUND: The level of adherence of various pharmacological therapies in chronic diseases varies, but is predominantly low. With tamoxifen (TAM), 23% and 50% nonadherence after 1 and 4 years have been reported. Day-to-day clinical observation suggests that adherence may even be lower with aromatase inhibitors, but limited data exist on the situation in daily clinical routine. The aim of this study was to evaluate the rate of adherent patients in a randomly selected sample of postmenopausal women with primary breast cancer, who had been assigned to an adjuvant endocrine treatment with TAM or anastrozole (ANA). MATERIALS AND METHODS: We investigated a random sample of 100 postmenopausal women with breast cancer (50 TAM and 50 ANA) who had received surgery for their primary breast cancer at our hospital in 2004/2005 and thereafter had been assigned to an adjuvant endocrine treatment. We evaluated the adherence rate with a detailed questionnaire and additionally carried out a retrospective prescription check of the hospital chart as well as calling the local physicians of our patients. A patient was counted as adherent with a self-reported tablet intake of 80% or more and if a medication possession ratio of 80% or more was achieved. RESULTS: Regarding the baseline characteristics, a significant difference in mean age was noticed in women on ANA versus TAM [65 (+/-3) and 72 (+/-3); P<0.001]. All women on TAM and ANA reported to be adherent (100%). After controlling for prescriptions, only 40 (80%) and 27 (69%) of the women on TAM and ANA were still classified as adherent (P<0.01 and P<0.01 versus self-report). We found no significant correlation of adherence to any baseline characteristics or side-effects in a logistic regression model. CONCLUSIONS: An important goal of any therapeutic intervention is to achieve comparable efficacy in routine clinical practice to that demonstrated in randomised clinical trials. However, a similar magnitude of adherence will be necessary in routine clinical practice to assure comparable clinical effects. Our results further support the data on suboptimal adherence of women with breast cancer on adjuvant TAM treatment. Here, we evaluated for the first time the patient reported and real-world adherence on adjuvant ANA and were able to show a similarly low adherence compared with TAM. More prospective studies are needed to increase our understanding of the underlying reasons for nonadherence in women with breast cancer.

[Clinical presentation and diagnosis of osteoporosis and osteomalacia]. / Klinik und Diagnostik der Osteoporose und Osteomalazie.

Osteoporosis and osteomalacia are systemic metabolic bone diseases characterized by an impaired composition, architecture, and quality of bone. In light of the demographic development and the recent use of sensitive tests, both diseases are increasingly diagnosed. Subjects at high risk include elderly, chronically hospitalized patients, and nursing home residents. Patients with gastrointestinal, rheumatologic and endocrine disorders are also at risk for the development of osteoporosis or osteomalacia. In this review, we will discuss practical aspects of the clinical presentation and the diagnosis of osteoporosis and osteomalacia.

The use of i. v. bisphosphonate in pregnancy-associated osteoporosis--case study.

OBJECTIVE: Diagnosis of pregnancy-associated osteoporosis is often delayed and therapeutic interventions insufficient. STUDY DESIGN: A 28-year-old patient (BMI=18.6) with no additional risks for osteoporosis experienced acute lumbosacral pain two months postpartum, while lactating. After conservative therapy, thoracic and lumbar spine were X-rayed: severe pregnancy-associated osteoporosis with vertebral fractures was diagnosed. 2-year treatment with i. v. bisphosphonate ibandronate was initiated (2 mg every 3 months) and calcium and vitamin D supplementation. RESULTS: Rapid improvement was observed. Conclusion: In cases with multiple fractures i. v. bisphosphonate leads to substantial decrease of symptoms and further fractures and significant increase of bone mass density (BMD). CONCLUSION: In severe cases of pregnancy-associated osteoporosis with multiple fractures i. v. biphosphonate therapy leads to a decrease of symptoms and fracture risk and an increase of bone mass density (BMD).

Bone mass and the risk of breast cancer: the influence of cumulative exposure to oestrogen and reproductive correlates. Results of the Marburg breast cancer and osteoporosis trial (MABOT).

BACKGROUND: Recent studies suggest an inverse relation between breast cancer and osteoporosis. Oestrogen is important in the pathophysiology of both breast and bone, and although cumulative exposure to oestrogen may explain the link between breast cancer and bone mass, this has never been proved. The Marburg breast cancer and osteoporosis trial (MABOT) aimed to elucidate the relation between breast cancer and bone mass ascertained by ultrasonometry measurement and to investigate whether endogenous and exogenous exposure to oestrogen and reproductive correlates has a role in this association. METHODS: We performed a case-control study including 2492 women (mean age+/-S.D., 54.4+/-10.3 years) in whom diseases and drug treatments known to affect bone metabolism, except for HT, had been excluded. All women underwent ultrasonometry measurement at the heel; 242 of the women had an incident breast cancer without a prior, specific pharmacological breast cancer treatment. The ultrasonometry variables - speed of sound (SOS), broadband ultrasound attenuation (BUA) and the stiffness index (SI) - were calculated and compared in women with and without breast cancer. Because of significant intergroup differences in factors such as age, body mass index and exposure to oestrogen, a multiple linear regression analysis as well as a second analysis of ultrasonometry variables was undertaken using a randomly selected sample of 242 healthy women post-matched with the breast cancer group for possible confounding variables. Odds ratios were used to compare the relation between breast cancer risk and ultrasonometry heel measurements. RESULTS: Women with breast cancer were significantly older, weighed more, had a higher body mass index, were more likely to be parous and to have breast fed, were older at the menopause and had been exposed to oestrogen for longer than control women. In addition, the ultrasonometry variables speed of sound and the stiffness index T- and Z-score were significantly higher in women with breast cancer even after a matched pair analysis was performed (p<0.001). Additionally, results of a multiple linear regression showed that women with breast cancer had a significantly higher SOS (p<0.001), body weight (p<0.05) and duration of breast feeding (p<0.05) while osteoporotic fracture were reduced (p<0.001). When women with breast cancer and their matched controls were finally grouped according to SOS and T-score quartiles, the odds ratios (95% confidence intervals) for breast cancer risk in the second, third and fourth quartiles compared with the lowest quartile were 2.5 (1.4-4.3), 3.1 (1.8-5.3) and 4.7 (2.7-8.2) as well as 1.9 (1.1-3.2), 2.3 (1.3-3.9) and 2.9 (1.7-5.0), respectively. CONCLUSIONS: The ultrasonometry variables speed of sound, stiffness index, T- and Z-score are higher in women with an incident breast cancer than in healthy controls, even after post-matching for possible confounding variables. This association was confirmed in a multiple linear regression model. Women with SOS and T-score values in the higher quartiles have a greater risk of breast cancer than women in the lowest quartile. We found no association between the higher ultrasonometry variables and cancer specific characteristics or reproductive correlates such as age at menarche and menopause or cumulative oestrogen exposure. Although the biological mechanisms linking bone mass and the risk of breast cancer are not fully understood, factors other than reproductive correlates, endogenous and exogenous exposure to oestrogen must play a part.

Biochemical markers of bone turnover during pregnancy: a longitudinal study.

OBJECTIVE: The objective of this study was to prospectively investigate the effect of pregnancy on biochemical markers of bone turnover in healthy pregnant women. METHODS: During the course of our longitudinal study, biochemical markers of bone remodeling were measured in all three trimester of pregnancy (first trimester: 12.5+/-1.8 SD, second trimester: 21.6+/-1 SD, third trimester: 34.8+/-1.6 SD weeks of gestation). Serum type I collagen C-telopeptides (CTX) and a crosslinked peptide of the carboxy-terminal telopeptide of type I collagen (ICTP) were used as markers of bone resorption. Bone alkaline phosphatase (BAP) and the N-terminal propeptides of type I collagen (PINP) were used as biochemical markers of bone formation. Blood samples for the analysis of all 4 biochemical markers according to each trimester of pregnancy were available in 49 patients. RESULTS: The main changes for all biochemical markers were seen between the second and the third trimester. According to the markers of bone resorption, both serum CTX and ICTP showed a significant increase from the first to the third and from the second to the third trimester (p<0.001; median percentage change: CTX=101.5% and ICTP=40%). Concerning markers of bone formation, PINP showed a significant decrease from the first to the second trimester (p=0.001) followed by a significant increase from the second to the third trimester (p<0.001, 63.8%) and an overall increase from the first to the third trimester (p<0.001). BAP also showed a significant increase from the second to the third trimester (p<0.001; 51.7%) and an overall increase from the first to the third trimester (p<0.001). CONCLUSION: Markers of bone resorption were significantly increased during pregnancy. In contrast to bone resorption, markers of bone formation showed an increase as well as a decrease during pregnancy indicating a state of high bone turnover. This might coincide with the change in bone mineral density that was observed in some, but not all, studies using "dual-energy x-ray absorptiometry" (DXA) as well as "quantitative ultrasonometry" (QUS).