Wilhelm Braendle

Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy.

In a large population‐based case–control study in Germany, including 3,464 breast cancer cases aged 50–74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face‐to‐face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%‐confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55–1.94) and heterogeneous by histological type (p < 0.01), being more than 2‐fold higher for lobular and tubular than for ductal cancer. Risks for current users varied significantly by type and regimen of HT, with ORs per year of use of 1.05 (95% CI, 1.04–1.06) for continuous combined estrogen–progestagen, 1.03 (95% CI, 1.02–1.04) for cyclical EP and 1.01 (95% CI, 1.00–1.03) for estrogen‐only therapy. No statistically significant increase in risk was observed after 5 years of cessation of HT use for any histological type. Analyses of progestagenic content by regimen revealed a significantly higher risk for continuously administered norethisterone‐ or levonorgestrel‐derived progestagens than for continuously administered progesterone‐derived progestagens (OR, 2.27, 95% CI, 1.98–2.62 vs. 1.47, 95% CI, 1.12–1.93, respectively, p = 0.003), which may be explained by dose rather than type of progestagen. These data suggest that the risks associated with menopausal HT differ by type and regimen of HT and histological type of breast cancer and may vary by progestagenic component, depending on the effective dose.

The Use of Herbal Preparations to Alleviate Climacteric Disorders and Risk of Postmenopausal Breast Cancer in a German Case-Control Study

Background:The use of herbal preparations (HEP) to alleviate climacteric disorders is expected to increase as women seek alternatives to menopausal hormone therapy to avoid the associated breast cancer risk. Data are sparse on the long-term effects of HEP containing phytoestrogens and black cohosh on breast cancer risk. Methods: Within a German case-control study, associations between patterns of HEP use and incident breast cancer were investigated in 10,121 postmenopausal women (3,464 cases, 6,657 controls). Information on HEP use was collected in face-to-face interviews supported by a list of brand names. Multivariate logistic and polytomous regression analyses were done. Findings: Ever use of HEP (9.9%) was inversely associated with invasive breast cancer [odds ratio (OR), 0.74; 95% confidence interval (CI), 0.63-0.87] in a dose-dependent manner (OR, 0.96 per year of use; P = 0.03). Classes of HEP did not differ significantly (Pheterogeneity = 0.81). Risks for invasive ductal (OR, 0.72; 95% CI, 0.60-0.87) and combined lobular/mixed/tubular tumors (OR, 0.76; 95% CI, 0.58-1.01) were similarly reduced by any HEP use but not for in situ carcinomas (1.34; 95% CI, 0.86-2.09). There were no substantial differences in associations of HEP use by estrogen receptor status (ER+ OR, 0.74; 95% CI, 0.62-0.89; ER− OR, 0.68, 95% CI, 0.50-0.93) and progesterone receptor status of the tumor. Interpretation: Our findings support the hypothesis that HEP use protects from invasive breast cancer in postmenopausal women. Among conceivable modes of action, those independent of estrogen receptor–mediated pathways seem to be involved (i.e., cytotoxicity, apoptosis). (Cancer Epidemiol Biomarkers Prev 2009;18(8):2207–13)

Polymorphisms in genes of the steroid receptor superfamily modify postmenopausal breast cancer risk associated with menopausal hormone therapy

Menopausal hormone therapy (HT) is associated with increased breast cancer risk among postmenopausal women. Nuclear receptors are involved in steroid hormone‐ and xenobiotic‐mediated signal transduction playing a crucial role in regulating gene expression. Therefore, variations within these genes may influence HT‐associated breast cancer risk. We investigated 3,149 postmenopausal breast cancer patients and 5,489 controls from 2 German population‐based case‐control studies. Thirty‐three polymorphisms selected on the basis of known or putative functional relevance located in ESR1, ESR2, PGR, PXR and AR were genotyped. Conditional logistic regression was used to assess multiplicative statistical interaction between polymorphisms and duration of estrogen–progestagen therapy and of estrogen monotherapy with regard to breast cancer risk assuming log‐additive and codominant modes of inheritance. We observed an increased risk for women carrying short AR_(CAG) alleles of <22 repeats associated with combined estrogen–progestagen therapy compared with those with long alleles (≥22 repeats) (pinteraction = 0.03). Additionally, risk associated with combination therapy use was significantly modified by 2 PXR polymorphisms with reduction of risk effects in carriers of the minor PXR_rs6785049_G and PXR_rs1054191_A alleles (pinteraction = 0.04 and 0.05, respectively). Variants in both ESR1 and ESR2 modified risk associated with estrogen monotherapy use. Higher risk were observed in homozygotes for the major ESR1_rs910416_T allele (pinteraction < 0.01) and in homozygotes for the minor ESR2_rs1271572_T, major ESR2_rs4986938_G and minor ESR2_rs928554_G alleles (pinteraction = 0.02, 0.05, 0.02, respectively). Risk effect modification by ESR1_rs910416 and AR_(CAG)n polymorphisms remained significant after correction for multiple testing. We conclude that genetic variants in nuclear receptor genes may modify HT‐associated postmenopausal breast cancer risk.

Menopausal Hormone Therapy and Risk of Clinical Breast Cancer Subtypes

Background: Breast cancer is a heterogeneous disease with subtypes that may vary in their etiologies. Menopausal hormone therapy has been associated more strongly with lobular and tubular than ductal histologic types and with tumors that are smaller, hormone receptor–positive, and of lower grade. At the same time, correlations have been observed between histology and clinical characteristics. To identify those tumor subtypes most strongly associated with hormone therapy use, it is necessary to disentangle these interrelationships. Methods: Based on 3,464 postmenopausal breast cancer cases and 6,657 controls from the population-based Mammary carcinoma Risk factor Investigation study, we used polytomous logistic regression to evaluate associations between hormone therapy use and risk of invasive breast cancer subtypes. We assessed variations in risk for selected tumor characteristics among histologic and hormone receptor subtypes, both overall and for specific hormone therapy regimens. Results: Lobular and mixed types showed less variation by prognostic factors than did ductal tumors. Current hormone therapy use had the strongest associations with prognostic variables in estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive ductal tumors and in lobular tumors regardless of ER/PR status, with little effect on ER/PR-negative ductal tumors. The observed associations varied minimally by hormone therapy type or regimen. Conclusion: Current hormone therapy use was associated with more favorable breast cancer characteristics for ductal tumors but had less effect on prognostic characteristics in women with lobular tumors. Both histologic type and estrogen receptor/progesterone receptor status seem to be important in explaining the role of hormone therapy in the etiology of breast cancer subtypes. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1188–96)

Ovarian Response and Pregnancy Rates in in vitro Fertilization, Gamete Intrafallopian Transfer, and in vivo Fertilization Therapies after Combined Gonadotropin-Releasing Hormone Agonist/Human Menopausal Gonadotropin Stimulation

Ovarian stimulation cycles were initiated using human menopausal gonadotropin (HMG) in 318 women (643 cycles) without pretreatment and in 341 women (525 cycles) after pituitary desensitization by pretreating with the gonadotropin-releasing hormone agonists (GnRH-A) buserelin acetate or triptorelin acetate. Significantly higher pregnancy rates were observed in the GnRH-A/HMG group (15%) as compared to the HMG group (7%) following in vitro (p less than 0.05) but not in vivo fertilization therapy (14 vs. 9%, respectively). After in vitro fertilization, the rates increased with increasing length of the active phase of follicular maturation. Gamete intrafallopian transfer, performed only in the GnRH-A/HMG group, led to a pregnancy rate of 34%. Overall, there was a clear trend to higher pregnancy rates in the GnRH-A/HMG group (16%) as compared to the HMG group (8%). Abortion rates were comparable in both groups (24 vs. 19%). The higher pregnancy rates in the GnRH-A/HMG group were attributable to enhanced follicular maturation and optimized ovarian stimulation produced by the hypogonadotropic state. However, an increased risk of the ovarian hyperstimulation syndrome was observed in these patients.

Kontrazeption bei Problemfällen

Thromboembolic, cardiovascular and cerebrovascular events are age-dependent. They are extremely rare in young women. In contrast to the progestogen-only pills, oral contraceptives (OC) increase the risk of venous thrombosis. However, decisive ist the genetic predisposition. In healthy non-smokers of less than 35 years of age, the risk to suffer from a myocardial infarction or a cerebrovascular accident is not increased by OC. Risk factors play a major role in the etiology of cardiovascular diseases. A detailed personal and family history is therefore mandatory before OC are prescribed. Very rarely, blood pressure is increased by OC. Although the incidence of such an increase is very low, blood pressure has to be measured regularly in pill users. Inspite of a current opinion, weight increase is rare in OC users. It depends mainly on the individual predisposition. An increased water retention can be reduced by a combined OC containing a progestagen with an antimineralocorticoid activity. Changes in insulin and blood sugar induced by low-dose OC are minimal so that they have no clinical relevance. OC do not increase the incidence of diabetes. Adrenal and thyroid function are not influenced by OC, there is no increased incidence of prolactinomas. Asthma is no contraindication against OC. If there is a cycle-dependent aggravation of the disease, OC might be beneficial. OC have no side-effects on the eye or the ear. In women suffering from lupus erythematodes having no renal participation, no increased antiphospholipid-antibodies and showing a stable or inactive disease, low-dose OC might be used.

Empfehlungen zur 3D-Sonographie in der Schwangerschaft

räumlichen Vorstellungsvermögen des Untersuchers zunächst unabhängiger ist. Ein weiterer Vorteil des 3D-Untersuchungsganges ist die Möglichkeit der nachträglichen Berechnung und Extraktion der verschiedensten Schnittbildoder Aufsichtsperspektiven aus dem gespeicherten Datensatz. Allerdings sind ähnlich wie bei der 2D-Ultraschalluntersuchung diese Perspektiven nur möglich, wenn sie aufgrund der anatomischen oder lagebedingten Gegebenheiten auch während der Datenaufnahme abbildbar sind. Die Untersuchung des fetalen Gesichts ist ein wichtiger Bestandteil der weiterführenden Ultraschalldiagnostik. Faziale Dysmorphien verbunden mit Entwicklungsstörungen sind ein wichtiges Hinweiszeichen vor allem auf Chromosomenaberrationen. Im 2D-Modus ist dafür eine grosse Anzahl von Schnittbildern notwendig, bei dem 3D-Untersuchungsverfahren kann eine realistischere Darstellung des fetalen Gesichtsprofils erzielt werden. Besonders in der Diagnostik der orofazialen Spaltbildungen sehen viele Untersucher einen Vorteil des 3D-Ultraschalls gegenüber der konventionellen 2D-Darstellung. Ausserdem ist auch hier eine nachträgliche oder auch simultane Analyse der verschiedensten 2D-Schnittebenen jederzeit möglich. Die 3D-Ultraschalluntersuchung bietet dem routinierten Untersucher zudem gewisse Vorteile bei der Darstellung der Nackentransparenz sowie der Wirbelsäule (Transparenzmodus) [5] .

Erhöht die hormonale Kontrazeption das Tumorrisiko

Als nicht-kontrazeptiven Nutzen senken orale hormonale Kontazeptiva (OH) das Risiko von bestimmten benignen und malignen Tumoren. Dazu gehoren benigne Brusttumoren, Uterusmyome und funktionelle Ovarialzysten. Eine Endometriose wird selbst durch OH nicht beeinflusst, doch kommt es zu einer Verminderung der Dysmenorrhoe. Bei nieder dosierten modernen OH scheint das Risiko fur Leberzelladenome und -karzinome nicht erhoht zu sein. Melanome werden durch OH nicht beeinflusst. Hinsichtlich des Mammakarzinoms kann aus den derzeit bekannten Daten kein erhohtes Risiko abgelesen werden. Auf das Endometriumkarzinom wirken OH langfristig protektiv, ebenso auf kolorektale Karzinome. Zervixkarzinome werden nicht direkt durch OH beeinflusst, jedoch wahrscheinlich durch ein unter OH anderes Sexualverhalten. Auch unter langjahriger OH-Einnahme fand sich keine erhohte Inzidenz von Neoplasien der Vagina oder Vulva.

Induction of Pharmacological Hypogonadotropism Using Gonadotropin-Releasing Hormone Agonists in Patients Undergoing Controlled Ovarian Stimulation

Pharmacological hypogonadotropism was induced in 167 women using the gonadotropin-releasing hormone agonists (GnRH-A) buserelin acetate or triptorelin acetate. 84 patients (group 1) began treatment using 1.2 mg/day buserelin acetate intranasally during the follicular phase (days 1-3); 41 patients (group II) began the same treatment, supported by 10 mg medroxyprogesterone acetate for 10 days, during the early luteal phase; 42 patients (group 3) received triptorelin acetate as an intramuscular depot injection, supported by 10 mg medroxyprogesterone acetate for 10 days, during the early luteal phase. Serum luteinizing hormone, follicle-stimulating hormone, oestradiol (E2), prolactin, and testosterone levels were monitored. Pituitary function was assessed by (1) measurement of endogenous luteinizing hormone fluctuation; (2) response to luteinizing hormone releasing hormone administration, and (3) response to oestradiol benzoate (E2 test). Complete pituitary desensitization was only assumed, if all three tests were negative. The LH-RH test and the E2 test were shown to be the most reliable indicator of pituitary function. E2 administration led to further reduction of gonadotropin secretion after pituitary desensitization. The desensitization time was 41.1 +/- 11.7 days in group 1 and was significantly reduced to 20.7 +/- 10.5 days in group 2 (p less than 0.01); a further, non-significant shortening to 15.1 +/- 3.0 days was observed in group 3. Changes in endocrine parameters demonstrated hypogonadotropic hypo-oestrogenism after initial pituitary stimulation.

Hormonale Kontrazeption – Dosierung und Verabreichungsformen

Seitdem der Zusammenhang zwischen der Dosis des Ethinylestradiols (EE) und dem Risiko venoser thromboembolischer Erkrankungen erkannt wurde, war die Entwicklung der Ovulationshemmer (OH) durch eine kontinuierliche Reduktion der EE-Dosis gepragt. Die damit verbundene Abnahme der Ovulationshemmwirkung der Estrogenkomponente wurde durch die Einfuhrung potenter Gestagene kompensiert, sodass die kontrazeptive Sicherheit bei geringerem Nebenwirkungsprofil erhalten blieb. Auf Akne und Seborrho haben auch ultra-niedrig dosierte OH einen gunstigen Einfluss. Die Ergebnisse zu den Wirkungen der ultra-niedrig dosierten OH auf das Skelett sind widerspruchlich. Da es zwischen Estradiol und EE fundamentale Unterschiede gibt, sinkt das thromboembolische Risiko bei parenteraler Gabe von EE nicht ab und nimmt beim kontrazeptiven Pflaster sogar zu. EE wird nicht an SHBG gebunden. Aufgrund der Ethinylgruppe wird EE relativ langsam inaktiviert, sodass auch das in gleichmasig niedrigen Konzentrationen in die Leber gelangende E...