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Advanced prostate cancer remains dependent on androgens and signaling through the androgen receptor despite castrate levels of testosterone defined as testosterone levels <1.7 nmol/l. Ketoconazole, a nonspecific inhibitor of androgen synthesis, has been tested in clinical trials and showed clinical activity; however, high doses are needed which are associated with significant sides effects, mainly neurotoxicity, gastrointestinal intolerance, and liver toxicity. Abiraterone acetate is an irreversible inhibitor of two key enzymes of androgen synthesis, 17a-hydroxylase and 17,20-lyase, and has been tested in a randomized phase III study in patients with castration-resistant prostate cancer who progressed after chemotherapy. Abiraterone plus prednisone resulted in a significant overall survival benefit of 4.6 months compared to prednisone alone. Abiraterone was well tolerated, with mostly mild or moderate side effects consistent with secondary mineralocorticoid excess, namely fluid retention, hypokalemia, and hypertension. Abiraterone plus prednisone is considered a new standard therapy option for patients with castration-resistant prostate cancer who progressed after chemotherapy.

After an average of 18-36 months under androgen suppression therapy by surgical castration, LHRH, and steroidal or non-steroidal antiandrogens, almost all patients with metastatic prostate cancer show PSA progression as a sign of androgen-independent but still androgen-sensitive tumor growth. Our understanding and the treatment of such castration-resistant prostate cancer has changed markedly. The introduction of new drugs like abiraterone and MDV3100 has shown that prostate cancer progression even in the"hormone-refractory" stage is driven by androgen receptor signaling. Based on this information the question of whether androgen deprivation therapy in castration-resistant prostate cancer should be continued or not is still of relevance. This review gives a critical overview of the literature and current guideline recommendations.

Chemotherapy options for the treatment of metastatic castration-resistant prostate cancer (CRPC) have been very limited for many decades. Until 2004, only mitoxantrone was approved, providing palliation, but no survival benefit. With the introduction of docetaxel, the landscape of chemotherapy for CRPC changed substantially. Prednisone and three-weekly docetaxel showed an overall survival (OS) benefit compared to mitoxantrone plus prednisone, in addition to a significant improvement of quality of life and pain reduction. Further strategies to treat CRPC with chemotherapy include reinduction with docetaxel in responding patients and the use of cabazitaxel, a novel semi-synthetic microtubule inhibitor, in the docetaxel-refractory population. This review article is meant to guide physicians through the optimal use of chemotherapy in CRPC patients in daily clinical practice.

Hereditary angioedema (HAE) is a rare, autosomal dominant disease due to functional deficiency of C1-esterase inhibitor (C1-INH). In this observational study anamnestic, clinical and treatment data from forty patients were retrospectively analysed. Thirty nine of the patients suffered from type I of HAE and one patient from type II. Between first manifestation of the disease and correct diagnosis a median time lag of 10 years was observed. Two C1-INH deficient individuals had no symptoms so far; 36 patients suffered from recurrent, self-limiting abdominal attacks (convulsion, vomiting and diarrhea); 32 patients presented with edema of the (sub-) cutis. Thirty percent of swelling attacks involved the upper respiratory tract and two larynx attacks needed intubation. Hormonal changes in 25% of the female patients were associated with an aggravation of the attacks. Long-term therapy was established in 19 patients; treatment of acute attacks was performed in 10 patients and 11 patients needed no therapy.

For more than 10 years, based on the results with the bisphosphonate clodronic acid, it has been discussed, whether the occurrence of breast cancer metastases can be avoided or at least delayed by administration of bisphosphonates. The published results of recent studies applying, e.g., the bisphosphonates zoledronic and ibandronic acid, respectively, seem promising at first glance, especially, if the therapeutic acceptance of bisphosphonates in the indications osteoporosis and bone-related complications of malignancies, respectively, as well as their spectrum of side effects are taken into account and their putative mechanism of action is considered. There is a broad consensus that the existing data basis suffices to demonstrate importance of bisphosphonates in an adjuvant therapeutic setting of breast cancer. Significant relative risk reductions of, e.g., 36% in disease-free survival are very impressing and the corresponding absolute values of 3.2% are second-line communications. However, evaluation of all studies published so far according to the criteria of evidence-based medicine demonstrates many open questions and several methodical insufficiencies. Therefore, effectiveness and benefit of an adjuvant therapeutic application of bisphosphonates in breast cancer patients cannot be drawn out of evidence-based data. A recommendation of this therapy is given only by the German Working Pool of Gynecologic Oncology (AGO), but limited to study participation.

In the last 30 years bisphosphonates have been used in the treatment of different bone diseases. Bisphosphonates in their oral pharmaceutical form are an established and approved medication in osteoporosis treatment for years. Latest research developed more potent bisphosphonates in different application forms: oral and parenteral. Therefore, their prospects for medical treatment could be enlarged to the fields of oncology, hematology, and osteology. Bisphosphonates are innovative in case of adjuvant therapy as well as in adequate pain therapy. In the medical treatment of osteoporosis and metabolic osteopathies bisphosphonates could be rightly denoted as groundbreaking.

History and Clinical Findings: A 15-year-old girl had suffered from episodic, sometimes threatening angioedema of the face, nasopharyngeal space and distal extremities beginning at age 13., Examinations: A C1-esterase inhibitor (C1-INH) deficiency was revealed protein-chemically and functionally. There was also an alpha (1)-antitrypsin (AAT) deficiency with heterocygotic phenotype PiMZ. The combination of C1-INH and AAT deficiency was also found in the patient's mother and brother., Therapy and Course: Under 8-month therapy with 200 mg/d danazol per os (reduction of the dosis in the last month to 100 mg/d), there was no further edema, the C1-INH concentration normalized and there was also an increase in C1-INH function. During the observation period, use of the emergency set with C1-INH concentrate was not required., Conclusions: This is the first reported case of angioedema in combination of two hereditary enzyme defects C1-INH deficiency (autosomal-dominant genetics) and AAT deficiency (autosomal-recessive). In addition to a survey of current literature, the current state of diagnostics and therapy of the hereditary angioedema is presented.

The therapy of postmenopausal osteoporosis is based on a few comprehensible assumptions. High bone resorption should be reduced by treatment with bisphosphonates, raloxifene or seldom with calcitonins. After reduction of high bone turnover and in low bone turnover situations, an osteoinductive combination therapy should be started, inducing collagen type I with parathyroid hormone or fluorides. This collagen can then be mineralized by calcium, vitamin D, and vitamin D metabolites. In addition, bone resorption should be reduced during menopause with estrogens and gestagens, in the case of a receptor-positive breast cancer with tamoxifen, and after menopause with raloxifene or a bisphosphonate. In elderly patients a depletion of vitamin D often induces an osteoporomalacia instead of an osteoporosis. In this situation, mineralization of the osteoid by calcium and vitamin D is sufficient for therapy. A daily osteoporosis gymnastic program is required and physical activity should be enhanced to increase muscle mass because bone adapts to the individual situation.

Modern treatment of cancer of the breast is based on established prognostic factors (patient age, receptor status, tumor size, lymph node involvement, tumor grading), and thus takes the patient's individual risk profile into account. In addition to the antiestrogen, tamoxifen, new hormonal preparations, such as the aromatase inhibitors, hold out promise of improved results from adjuvant treatment in elderly women. In premenopausal women, additional hormone blockade by means of GnRH analogs is of advantage. Neoadjuvant (preoperative) chemotherapy protocols will enable rapid evaluation of new therapeutic options. When metastases have developed, treatment with hormonal drugs is indicated in the case of slowly progressing disease (low risk), while clinically progressive metastasization (high risk) requires cytostatic chemotherapy. Here, studies involving more recent substances with improved tolerability, and tumor-specific antibodies, confirm an improvement in the prognosis. The concentration of drug treatment in interdisciplinary centers is a necessary element of quality assurance and therapeutic optimization.

The actual methods of postcoital emergency contraception are described and compared. The method of choice is the administration of a progestagen-only pill because this method is more reliable and effective than the use of a combined estrogen-progestagen pill ("Yuzpe-Method"), and because the incidence of side-effects is considerably lower. The results obtained with levonorgestrel alone are presented by the authors. The postcoital introduction of a copper intrauterine device is highly effective, but invasive. This method is indicated if it is too late to use the pill. An open and accepting setting of the consultation and a way of taking the medical history that is pointing to the auto-responsibility are essential, especially for adolescents. Low conditions for the admission to the counselling are postulated, and the obligation to possess a medical prescription to obtain the only progestagen-only pill is questioned.

For many years, hormone replacement therapy (HRT) has been regarded as one of the most reliable means of prophylaxis and treatment for postmenopausal osteoporosis. As HRT ameliorates menopausal symptoms, it is widely prescribed among early postmenopausal women. A variety of different modes of replacement that suit each individual requirement are available in terms of schedule (cyclic or combined application of gestagens) and route of application (oral or transdermal). HRT effectively prevents spinal bone loss and delays bone loss at the hip up to a very old age. With continued use after menopause, HRT might theoretically halve the incidence of vertebral and hip fractures. However, long-term use or use of HRT in old age is rarely practiced, and the actual benefit of a transient use for future fracture prevention remains unclear. Raloxifene is the first member of the novel class of selective estrogen receptor modulators (SERMs) that has been approved for the prophylaxis and treatment of postmenopausal osteoporosis. It combines the positive effects of estrogen on the skeleton with estrogen-antagonistic effects on sex tissues. Thus, raloxifene maintains bone mass and decreases the incidence of vertebral fractures in osteoporotic women, but avoids many of the side effects that are responsible for the poor long-term compliance to HRT such as resumption or continuation of regular menses, breast tenderness, or breast cancer. It even markedly reduces the risk of breast cancer. Both estrogen and raloxifene are characterized by a large number of extraskeletal effects that have to be taken into account when counseling postmenopausal women on the use of these agents for the prevention or treatment of osteoporosis.

History and Clinical Findings: A 35-year-old man, for 8 years known to have hereditary angio-oedema with recurrent cutaneous swellings and occasional attacks of gastrointestinal pain, developed very painful, colic-like upper abdominal symptoms and frequent vomiting., Investigations: Routine laboratory tests were normal, except for leucocytosis of 18,200 WBC/microliter. The plasma concentrations of C1-esterase inhibitor (5.6 mg/dl) and of complement factor C4 (10.0 mg/dl) were reduced. Computed tomography revealed about 500 ml free fluid, a perihepatic effusion and definite oedematous thickening of the ileal wall., Treatment and Course: During conservative treatment with infusions and no food by mouth the symptoms regressed. Abdominal ultrasonography was normal (no free intraabdominal fluid). Since discharge (now more than 15 months ago) the patient has been on danazole medication (200 mg/d)., Conclusion: Recurrent gastrointestinal colics are typical of for hereditary angio-oedema and can imitate an acute abdomen. Concurrent ascites has only recently been described. Appropriate instruction of the patient and his/her medical practitioner is important to avoid unnecessary laparotomy.

In patients with metastatic breast cancer, cure is almost always an exception, irrespective of the therapy given. Thus the preservation of the quality of life or palliation in case of symptoms must be the principal goal. Only a small group of patients with their tumour showing a highly aggressive behaviour should be considered for primary chemotherapy. Aggressive tumour growth is then characterized by negative hormonal receptors, short disease-free interval and predominant visceral tumour growth. For all other patients there is not enough advantage to justify the clearly higher toxicity of a primary chemotherapy. This majority of patients with metastatic breast cancer can profit to a higher degree from hormonal treatment. Irrespective of the type of the hormonal therapy, the response rate is positively correlated with postmenopausal status, high hormonal receptor expression, al long disease-free interval, no previous adjuvant therapy and higher age. Advantages and problems of the various forms of hormonal manipulations are discussed. The recommended sequence of therapy represents only a handrail that needs to be adjusted carefully, according to the individual situation, the needs and expectations of the patient and in due knowledge of the toxicity of each hormonal substance. Combinations of different hormonal agents do not yield an additional benefit and should therefore be dropped for a sequential approach.

The aim of this study is to obtain an actual survey of diagnostic and therapeutic procedures of endometriosis (EMT) in gynaecological practice in West Germany. A questionnaire was sent to 6,700 gynaecologist; 1,364 responded. Approximately 5% of all the patients in daily practice have symptoms related to EMT. Most of the patients are in their twenties. The common clinical symptoms of EMT are dysmenorrhoea (91.8%), infertility (79.7%), pelvic pain (70.9%), menstrual irregularity (46.3%), dyspareunia (21.8%) and painful defaecation (12.8%). The diagnostic standard is laparoscopy, but there are many doctors diagnosing EMT also by means of gynaecological examination (23.8%) or ultrasound (21.3%) - especially in young patients. Hormones are the first choice of therapy. Progestins and danazol are preferred. GnRH-analogues are only used by a smaller proportion of gynaecologists - particularly in infertile patients. Surgical procedures with or without hormonal suppression are another line of therapy adapted by 70.9% of the gynaecologists, which are often preferred in infertile patients. Psychological problems in EMT are caused by the uncertainties between EMT and infertility and by the difficulties between physiological menstrual discomfort and pain caused by EMT. 68.5% of the gynaecologists suggest that more information beyond diagnosis and therapy should be given to the patients. Promotion of self-supporting groups should be encouraged by the doctors.

To avoid an operation, there are innumerable pharmaceutics on sale for the treatment of the benign prostatic hyperplasia. For this reason we have to distinguish between pharmaceutics without effect and those with proved action on the hyperplastic metaplasia. The symptoms can often be lessened at the initial stage by way of drugs with ineffective action (phytopharmaceutics); there could not yet be proved any effect on the biology of the prostatic hyperplasia. We make use of this therapeutic at the initial stage. Some of the substances with a real effect (alpha-receptor blockers, alpha-reductase inhibitors) do not necessarily provide an effective result in all cases. In addition to that, these therapeutics of partially serious side effects have to be taken for life. Here immediately arises the question of how it could be managed financially.

The efficacy of treatment for benign prostatic hyperplasia (BPH) is presently under critical consideration. In addition, various new therapeutic modalities are currently being evaluated. When medicamentous treatment is planned, in particular, the natural history of the disease must be carefully considered. Summarized data from several studies indicate that spontaneous improvement of symptoms may occur within 3-6 months, while in most cases deterioration takes a longer period of time. As intraprostatic urethral pressure depends on prostatic volume as well as on tone of the prostate smooth muscle, different medical treatment modalities seem reasonable. The dynamic component of the smooth muscle cells may be influenced by alpha-blockers. Administration of selective alpha 1-blockers will be advantageous as these have fewer side effects. Prostate volume represents the static component, which can be influenced by hormone treatment. Androgen deprivation via surgical castration must now be regarded as of historical interest only. Antiandrogens or LH-RH analogues have undesirable side effects and are expensive, making such treatment unacceptable for routine use. 5 alpha-Reductase inhibitors may emerge as a new treatment form allowing androgen suppression with a low rate of side effects. As it has been proposed that estrogens play an important role in the regulation of prostatic growth, aromatase inhibitors, which inhibit metabolization from androgens to estrogens, may receive special attention in the near future. Based on the theory that androgens may be of special importance for the epithelium, while estrogen action may be concentrated on the stroma, a combined treatment with inhibitors of 5 alpha-reductase plus aromatase may be even more effective.(ABSTRACT TRUNCATED AT 250 WORDS)

In this review several possibilities of an individualized hormonal therapy of the advanced breast cancer are discussed. Tumors selected for hormonal therapy on the basis of a positive estrogen receptor respond to endocrine therapy at nearly twice the rate of those chosen by clinical criteria alone. The overall response can be predicted with an accuracy of about 75 per cent. Furthermore clinical tests like short time treatment with L-dopa or testosterone are liable for many subjective mistakes. If the multivalent analyse of various prognostic criteria will be better for predicting the mistakes. If the multivalent analyse of various prognostic criteria will be better for predicting the hormone sensitivity is up to now unknown. The paper gives several guides for the ablative and additive hormonal therapies.

38 patients with metastasizing breast cancer who were stratified according to prognostic criteria were treated with high-dose medroxyprogesterone acetate (MPA). The response rate in our series was nearly 50 percent. The indication for high-dose gestagen therapy as well as anti-tumor activity and side effects are discussed by comparing our results with recent communications in the literature.

Determination of the tissue concentration of hormone receptors in gynaecological malignancies has achieved a great importance over the past few years. In carcinoma of the breast this not only constitutes an excellent prognostic parameter, receptor-positive cases usually having a much better prognosis, but also reliably predicts the response to endocrine treatment: the higher the receptor concentration, the higher the remission incidence under hormonal treatment. With regard to the response to chemotherapeutic treatment the predictive value of receptor determinations is still a matter of dispute. In both carcinoma of the breast and carcinoma of the endometrium there is a good correlation between the degree of differentiation and the concentration of receptors. Since the response to treatment with progestational agents depends on the concentration of progesterone receptors, induction of this receptor by means of antioestrogenic medication can be used therapeutically. In ovarian carcinoma a similar distribution of hormone receptors is found. Whether receptor concentration in ovarian carcinoma is related to prognosis and response to endocrine treatment is still under investigation. It can be assumed that determination of hormone receptor concentrations will become an integral part of the management of gynaecological malignancies.

Basing on the mechanism of the endocrine regulation of the reproductive events in the women causes and therapy of the endocrine sterility are discussed. Causes of endocrine sterility are divided into the entities hyperprolactinemic, hyperandrogenemic, hypo- and dysgonadotropic hypogonadism. Concerning these disturbances the specific therapeutic opportunities with the inhibitor of the prolactin secretion, with antiandrogenes, corticosteroids, antiestrogens, gonadotropins or gonadotropin-releasing hormone, respectively, are summarized. With a proposed scheme for diagnostic and therapeutic use an effective and economic proceeding in the treatment of the endocrine caused female sterility is intended.

Estradiol receptors which are detectable in the cytoplasma of cells of human breast cancers can be used successfully for evaluating the hormone sensitivity of these tumours. Receptor negative cancers generally do not respond to endocrine therapeutical procedures whereas receptor positive cancers respond in 60% of cases. It is conceivable that this non sufficient correlation is caused by an impairment in the hormone receptor interaction, The simultaneous determination of estradiol and progesterone receptors in the tumour tissues increases the correlation between receptor status and hormone sensitivity to 80 percent. There exists a high degree of conformity between the receptor status of primary tumours and metastatic lymph nodes as well as recurrences.