Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer.

PURPOSE: There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA. METHODS: Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed. RESULTS: Time to CRPC [p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC (p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months (p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT (p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year (p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy. CONCLUSIONS: Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.

Clinical, hormonal and metabolic parameters in women with PCOS with different combined oral contraceptives (containing chlormadinone acetate versus drospirenone).

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5-10% of women of reproductive age. It is characterized by chronic anovulation leading to menstrual disorders, and increased infertility. The syndrome can also manifest as hirsutism and acne. AIM OF THE STUDY: The aim of the study was to compare, over a duration of 6 months, the effects of drospirenone (DRSP) versus chlormadinone acetate (CMA) containing oral contraceptives (OCs) on clinical, hormonal, and metabolic parameters in 120 PCOS women. MATERIALS AND METHODS: 120 women with the diagnosis of PCOS according to the Rotterdam 2003 criteria were recruited to the study. All patients were divided to two treatment groups of OCs, containing: 3 mg DRSP/30 mcg EE (ethinylestradiol) (60 patients) and 2 mg CMA/30 mcg EE (60 patients). Clinical parameters such as hirsutismus and acne were evaluated. Metabolic parameters such as serum insulin, glucose concentration, homeostatic model assessment of insulin resistance, body mass index, systolic and diastolic blood pressures were also measured. Among hormonal parameters, serum estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, dehydroepiandrosterone sulfate, thyroid-stimulating hormone, and free thyroxine were measured. RESULTS: The use of both DRSP- or CMA-containing OCs provided similar positive therapeutic effects with regard to clinical, metabolic, and hormonal parameters. Among clinical parameters, like hirsutismus, after 6 months of continuous OC treatment, a statistically significant improvement was observed in both groups: DRSP (p < 0.0001) and CMA OC treatment (p < 0.0001). In addition, significant improvement was showed according to acne lesions both after DRSP (p < 0.0001) and CMA treatments (p < 0.0001). Among glucose, insulin levels and HOMA-IR, there were statistically significant higher levels in both groups after DRSP (p < 0.0001, p < 0.0001, p < 0.05) and CMA OC treatment (p < 0.02, p < 0.0001, p < 0.0001). Hormonal parameters such as LH, FSH, prolactin, testosterone and DHEA-S were statistically significant lower in both groups after DRSP (p < 0.0001, p < 0.0001, p < 0.01, p < 0,002, and p < 0.0001) and CMA OC treatment (p < 0.0001, p < 0.0001, p < 0.04, p < 0.002, and p < 0.0001). CONCLUSIONS: Further research, however, is needed not only to define optimal duration, and to clarify the effects of treatment on long-term metabolic outcomes, but also to explore different treatment options and possible combined therapies.

The effects of osaterone acetate on clinical signs and prostate volume in dogs with benign prostatic hyperplasia.

A clinical trial was performed to evaluate the therapeutic efficacy of osaterone acetate (OSA) in the treatment of benign prostatic hyperplasia (BPH) in dogs. Osaterone acetate (Ypozane, Virbac) was administered orally at a dose of 0.25 mg/kg body weight once a day for seven days to 23 dogs with BPH. During the 28-day trial, the dogs were monitored five times for their clinical signs and prostate volume. The OSA treatment promoted rapid reduction of clinical scores to 73.2% on day 7 and to 5.9% on day 28 (p⟨0.05). Osaterone acetate induced the complete clinical remission in approximately 83.0% of the dogs on day 28. The prostate volume regressed to 64.3% of the pretreatment volume after two weeks of the treatment (p⟨0.05) and to 54.7% at the end of the trial (p⟨0.05). In conclusion, OSA quickly reduced clinical signs and volume of the prostate glands in dogs with BPH.

Effects of Steroidal Antiandrogen or 5-alpha-reductase Inhibitor on Prostate Tissue Hormone Content.

BACKGROUND: The effects of a steroidal antiandrogen (AA) and 5-alpha-reductase inhibitor (5ARI) on prostate tissue hormone content and metabolism are not fully elucidated. The objective of this study is to investigate the hormone content and metabolism of the prostate tissues of patients treated with AA or 5ARI using the ultra-sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. METHODS: Thirty-nine patients with benign prostatic hyperplasia (BPH) undergoing transurethral surgery were included. Serum and prostate tissue hormone and prostate tissue hormone metabolism analyses were performed using LC-MS/MS after 1 month of treatment with chlormadinone acetate (CMA; steroidal AA, 50 mg/day) or dutasteride (DUTA; dual 5ARI, 0.5 mg/day). RESULTS: Serum testosterone (T), dihydrotestosterone (DHT), and adrenal androgen levels were lower in the CMA group than the control group. Prostate tissue T and DHT levels were also lower in the CMA group than the control group. In the DUTA group, only serum and prostate DHT concentrations were reduced compared to the control group; in contrast, those of other hormones, especially T and 4-androstene-3,17-dione in the prostate tissue, showed marked elevations up to 70.4- and 11.4-fold normal levels, respectively. Moreover, the hormone metabolism assay confirmed that the conversion of T to DHT was significantly suppressed while that of T to 4-androstene-3,17-dione was significantly accelerated in the prostate tissue of DUTA-treated patients. CONCLUSIONS: Although treatment with AA and 5ARI show similar clinical outcomes, their effect on tissue hormone content and metabolism varied greatly. Prostate 77: 672-680, 2017. © 2017 Wiley Periodicals, Inc.

Suppression of the Hypothalamic-pituitary-adrenal Axis by Maximum Androgen Blockade in a Patient with Prostate Cancer.

A 78-year-old Japanese man showed suppression of the hypothalamic-pituitary-adrenal axis during maximum androgen blockade (MAB) therapy including chlormadinone acetate (CMA) for prostate cancer. After stopping the MAB therapy, both the basal ACTH level and the response to CRH recovered. While no reports have indicated that CMA suppresses the hypothalamic-pituitary-adrenal axis in patients with prostate cancer, CMA has been shown to inhibit this axis in animals. These observations suggest that we must monitor the hypothalamic-pituitary-adrenal axis in patients treated with CMA, especially under stressful conditions.

[Transient, secondary hypoadrenocorticism after treatment with delmadinone acetate (Tardastrex®) in a two year old male dog]. / Transienter, sekundärer Hypoadrenokortizismus nach Behandlung mit Delmadinonacetat (Tardastrex®) bei einem zwei Jahre alten Rüden.

INTRODUCTION: A two year old male Labrador Retriever was treated with delmadinone acetate because of benign prostatic hyperplasia. Four days after the injection the dog showed gastrointestinal signs and a progressive lethargy. In the hospital for small animals of the Justus-Liebig-University of Gießen an ACTH stimulation test was done and a secondary hypoadrenocorticism was diagnosed. The dog was treated with prednisolone in physiological dose for 14 weeks after the injection. The clinical symptoms stopped immediately. A new ACTH stimulation test some weeks later showed a completely normal adrenal function.

DIAGNOSIS AND MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA IN A PIED TAMARIN (SAGUINUS BICOLOR).

An intact male pied tamarin (Saguinus bicolor) presented with a hunched posture while moving, dysuria, pollakiuria, and hematuria. After diagnostic imaging assessment and prostate biopsy, benign prostatic hyperplasia was diagnosed. Treatments with delmadinone acetate and osaterone caused clinical signs and hematuria to resolve temporarily for a variable period of time. Because of frequent recurrence, elective surgical castration was performed, leading to resolution of the clinical signs.

Effect of oral contraceptives containing estradiol and nomegestrol acetate or ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea.

OBJECTIVE: To study the three cycles effect on primary dysmenorrhea of the monophasic 24/4 estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl-estradiol/chlormadinone acetate (EE/CMA) oral contraceptive. The tolerability and the effect of both preparations on metabolism and health-related quality of life were also evaluated. DESIGN: Prospective observational cohort study. SETTING: Tertiary gynecologic center for pelvic pain. PATIENTS: Subjects with primary dysmenorrhea requiring an oral contraceptive, who spontaneously selected either E2/NOMAC (n = 20) or EE/CMA (n = 20). MAIN OUTCOME MEASURES: Visual Analogue Scale (VAS) score for dysmenorrhea, Short Form-36 questionnaire for health-related quality of life, lipoproteins and days of menstrual bleeding (withdrawal bleeding during oral contraceptive). RESULTS: Mean age and body mass index (BMI) were similar between the two groups. The final analysis was performed on 34 women, 15 in E2/NOMAC and 19 in EE/CMA group. Compliance with treatment was significantly higher with EE/CMA (100%) than E2/NOMAC (75%) (p = 0.02). Both treatments significantly (p < 0.0001) reduced VAS of primary dysmenorrhea, similarly (E2/NOMAC by a mean of 74.7%, EE/CMA by a mean of 78.4%; p = 0.973). Only E2/NOMAC significantly increased SF-36 score (p = 0.001), both in physical (p = 0.001) and mental domains (p = 0.004). The mean number of days of menstrual bleeding was significantly reduced in E2/NOMAC group (from 4.86 ± 1.20 d to 2.64 ± 1.59 d, p = 0.0005 versus baseline, p = 0.007 versus EE/CMA group). BMI did not vary in either group. E2/NOMAC did not change lipoproteins and apoproteins while EE/CMA increased total cholesterol (p = 0.0114), HDL-cholesterol (p = 0.0008), triglycerides (p = 0.002), apoprotein-A1 (Apo-A1; p = 0.0006) and apopoprotein-B (Apo-B; p = 0.008), decreasing LDL/HDL ratio (p = 0.024). CONCLUSIONS: Both oral contraceptives reduced similarly primary dysmenorrhea, with E2/NOMAC also reducing withdrawal bleedings and being neutral on lipid metabolism.

Comparison of the effects of chlormadinone acetate versus drospirenone containing oral contraceptives on metabolic and hormonal parameters in women with PCOS for a period of two-year follow-up.

OBJECTIVE: A randomized trial to compare the effects of two oral contraceptive pills containing either chlormadinone acetate or drospirenone as the progestogen, in women with PCOS for a period of two-year follow-up. METHODS: Group A received ethinyl-estradiol 0.03 mg + drospirenone 3 mg (EE + DRSP; n = 56) and Group B received ethinyl-estradiol 0.03 mg + chlormadinone acetate 2 mg (EE + CMA; n = 50). Clinical, hormonal and biochemical parameters were compared at baseline, 6 months, 12 months and 24 months. RESULTS: The increase in total cholesterol and hsCRP levels was statistically significantly higher at 6, 12 and 24 months in Group B when compared with Group A. The change in the high-density lipoprotein cholesterol level at the 24 months of treatment was statistically significantly higher in Group A. Group A has a significantly higher reduction in FAI at 6 and 24 months, in FGS at 6, 12 and 24 months and in HOMA-IR index at 12 and 24 months when compared with Group B. CONCLUSIONS: Drospirenone containing combined oral contraceptive (COC) is found to have more favorable effects on lipid profiles, hsCRP levels, insulin resistance and hyperandrogenism when compared with the CMA containing COC and appears to be more beneficial for the long-term cardiovascular and metabolic aspects of PCOS.

Conditional PTEN-deficient mice as a prostate cancer chemoprevention model.

BACKGROUND: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). MATERIALS AND METHODS: Six-week-old mice were treated subcutaneously with 50 µg/g of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. RESULTS: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. CONCLUSIONS: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.

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.

An open trial of long-term testosterone suppression in spinal and bulbar muscular atrophy.

INTRODUCTION: We investigated the long-term effects of leuprorelin on leg-muscle strength in spinal and bulbar muscular atrophy (SBMA). We hypothesized that testosterone suppression by leuprorelin would prevent the progression of muscle weakness. METHODS: In a prospective, long duration, open trial, 16 SBMA patients underwent medical castration with leuprorelin for 3.5 years. Chlormadinone was coadministered initially to prevent a testosterone surge. The strength of knee extension and flexion were quantitated using a torque machine. RESULTS: Our hypothesis was rejected. The leg strength measures decreased significantly with the mean reduction of 22.3-27.8%. In a post hoc analysis, the leg strength of 4 patients with higher pretreatment baseline total testosterone levels and short disease duration of 1-6 years were stronger at baseline and decreased by only 12.3-15.7% after treatment. CONCLUSIONS: Leuprorelin was not effective in this small long-term treatment trial in SBMA. The possibility that earlier treatment might be beneficial may deserve further study.

Oral contraceptive containing chlormadinone acetate and ethinylestradiol reduces plasma concentrations of matrix metalloproteinase-2 in women with polycystic ovary syndrome.

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 µg ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.

The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with metabolic dysfunction and changes in cardiovascular risk markers, and using oral contraceptives (OCs) may exert a further negative effect on these alterations in patients with PCOS. Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS. STUDY DESIGN: This was a randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35 years of age were randomized by a computer program to use OC or OC+SPL. Brachial artery flow-mediated vasodilation, carotid intima-media thickness and the carotid artery stiffness index were evaluated at baseline and after 6 and 12 months. Serum markers for cardiovascular disease were also analyzed. The intragroup data were analyzed using analysis of variance with Tukey's post hoc test. A multivariate linear regression model was used to analyze the intergroup data. RESULTS: At 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables. CONCLUSION: The addition of spironolactone to an OC containing chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk-marker advantages in young women with PCOS.

Evaluation of efficacy, safety and effects on symptoms of androgenization of a generic oral contraceptive containing chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg.

BACKGROUND: This prospective noninterventional study assessed the contraceptive efficacy, safety and the effects on signs of androgenization of the generic oral contraceptive containing 2 mg chlormadinone acetate/0.03 mg ethinylestradiol (CMA/EE) in a real-world setting. STUDY DESIGN: A total of 1440 women were investigated during a six-cycle period by 229 gynecological practices throughout Germany. RESULTS: The adjusted Pearl index was 0.136 (unadjusted: 0.271). Of 463 patients with cycle irregularities at baseline, 83.4% had regular cycles after six cycles. Likewise, 74.1% of 162 patients with spotting or breakthrough bleeding at baseline were free from these symptoms at the end of study. The percentage of patients with dysmenorrhea decreased significantly from baseline (36.5%) to visit 3 after six cycles (12.3%; p=.0001), with a significant reduction in the use of pain medication (p<.0001). Additionally, the number of patients with skin and hair problems was significantly reduced (skin: 56.3% at baseline, 19.6% after six cycles; hair: 45.7% at baseline, 13.4% after six cycles; p=.001). CMA/EE was well tolerated by the patients, and 89.44% of the gynecologists were satisfied with the treatment. CONCLUSION: Generic CMA/EE exhibits very good contraceptive efficacy, cycle control and dysmenorrhea reduction. Furthermore, treatment with generic CMA/EE led to a favorable reduction of skin and hair problems in our study.

Ethinylestradiol/Chlormadinone acetate: dermatological benefits.

Acne vulgaris, hirsutism, seborrhea and female pattern hair loss (FPHL) are common disorders of the pilosebaceous unit (PSU). In some women with hyperandrogenemia, an excess of androgens at the PSU can lead to the development of these dermatological manifestations. These manifestations can cause many psychiatric and psychological implications, such as social fears and anxiety, and can adversely affect quality of life. High androgen levels at the PSU as a possible underlying cause of acne vulgaris, hirsutism, seborrhea and FPHL supports the rationale for using combined oral contraceptives for the management of these conditions in women. The purpose of this review is to describe these dermatological manifestations of the PSU and the management of these conditions through the use of the oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA). EE/CMA 0.03/2 mg is a combined monophasic contraceptive pill with anti-androgenic properties. It is approved in Europe for contraception and has been investigated in phase III trials for the treatment of acne. EE/CMA was better than placebo and similar to another low-dose oral contraceptive (ethinylestradiol/levonorgestrel) in improving symptoms of acne in two phase III randomized controlled trials in patients with mild to moderate papulopustular acne. In addition, in trials investigating the contraceptive efficacy of EE/CMA, limited data suggest that there were also improvements in hirsutism, FPHL and seborrhea in small subgroups of patients. EE/CMA has a good safety profile. The most commonly reported adverse events are breast tenderness/pain, headache/migraine and nausea. Evidence in the literature indicates that the use of EE/CMA for the treatment of dermatological disorders under the control of androgens may be a valid treatment option. Further investigation is warranted.

Ethinylestradiol/Chlormadinone acetate for use in dermatological disorders.

The diagnosis and management of four cases of dermatological disorders, most of which are related to the endocrine disorder of androgen excess, are presented. Combined oral contraceptives (COCs) may be useful when well-tolerated hormonal therapy and/or when contraception is required. A female patient with androgenetic alopecia or female pattern balding, without underlying hyperandrogenism, was treated with ethinylestradiol/chlormadinone acetate (EE/CMA) 0.03 mg/2 mg for 6 months and experienced stabilization of hair loss (case report 1). A patient who had previously received a COC for an irregular menstrual pattern but again experienced irregular menses and also acne after stopping treatment was diagnosed with acne associated with polycystic ovary syndrome (PCOS) [case report 2]. After 6 month's treatment with EE/CMA 0.03 mg/2 mg, this patient had fewer acne lesions and became eumenorrheic. A third patient who had excess hair since childhood was diagnosed with idiopathic hirsutism (no underlying gynecological or endocrinological disorder was found) and was treated with EE/CMA 0.03 mg/2 mg (case report 3). Less hair growth was reported after 6 months' treatment. Case report 4 describes a patient who presented with oligomenorrhea and acne. She was diagnosed with PCOS with acne, seborrhea and mild hirsutism. Treatment with EE/CMA 0.03 mg/2 mg for 6 months resulted in improvements in her facial acne, seborrhea and hirsutism; she also became eumenorrheic. These four cases illustrate that EE/CMA may be a useful and well tolerated treatment option in the management of patients with dermatological disorders with or without hyperandrogenization.

[Changes in serum prostate specific antigen and testosterone levels after chlormadinone acetate treatment in patients with benign prostatic hyperplasia : a prospective multicenter clinical study].

In this prospective multicenter study, we investigated the changes in serum prostate-specific antigen (PSA) and testosterone levels after treatment with antiandrogen chlormadinone acetate (CMA) in patients with benign prostatic hyperplasia (BPH). The inclusion criteria for the patients were as follows : PSA value of C10 ng/ml, maximum urine flow rate of ＜15 ml/s, estimated prostate volume of B20 ml, International Prostate System Score (IPSS) of B8, and IPSS-quality of life (QOL) index of B2. Of the 115 patients who registered, 114 qualified for this study. The patients were treated with CMA (50 mg/day) for 16 weeks ; this was followed by a no-CMA phase of 32 weeks. When compared with the baseline PSA level, the levels at 8 and 16 weeks of treatment had decreased by 56.4% (95% confidence interval [CI], 51.1-1.2) and 57.6% (95% CI, 52.3-62.4), respectively. Similarly, when compared with the baseline testosterone level, the levels at 8 and 16 weeks of treatment had decreased by 90.1% (95% CI, 87.8-91.9) and 84.4% (95% CI, 80.7-87.4), respectively. After treatment discontinuation, the PSA levels gradually increased and returned to baseline in 32 weeks. However, the testosterone levels returned to baseline in only 8 weeks. Although patients over 80 years of age showed a gradual decrease in these levels when compared with younger patients, the changes in the levels of PSA and testosterone were not affected by age. Thus, in order to use antiandrogen agents including CMA for treating BPH, we need to determine the PSA value that converted it into double.

Safety data and beneficial effects of the combined oral contraceptive ethinylestradiol 0.03 mg/chlormadinone acetate 2 mg (Belara®): a 13-cycle, observational study in routine clinical practice.

BACKGROUND: The monophasic hormonal combined oral contraceptive (COC) ethinylestradiol (EE) 0.03 mg/chlormadinone acetate (CMA) 2 mg (Belara®) has been shown to have good long-term efficacy and tolerability. OBJECTIVES: The aim of this study was to corroborate the long-term safety of EE 0.03 mg/CMA 2 mg by evaluating the incidence and severity of adverse drug reactions (ADRs) and cycle control over 13 treatment cycles. Additionally, the influence of EE 0.03 mg/CMA 2 mg on dysmenorrhoea, acne and the well-being of subjects was also investigated. METHODS: This observational study was conducted in Spain, France and Italy from April 2006 to August 2008. Subjects of reproductive age, without contraindications mentioned in the current summary of product characteristics, were prescribed EE 0.03 mg/CMA 2 mg in routine clinical practice. RESULTS: 3771 subjects were analysed and at least one ADR was reported in 833 (22.1%) subjects, with the majority of ADRs (75.6%) being judged as mild or moderate. The most frequently reported ADRs were intermenstrual bleeding (7.7% of all analysed subjects), headache (5.1%) and breast pain (2.7%). Spotting and breakthrough bleeding (defined as slight and heavier intermenstrual bleeding) at baseline were reported by 677 (18.0%) and 268 (7.1%) subjects, but were less frequent in cycles 10-13 (9.6% and 1.7%, respectively). Before study start, 61.8% of subjects suffered from dysmenorrhea, with the intensity being moderate or severe in 66.9% of these subjects. In cycles 10-13, the corresponding values were noted in 15.0% and 25.6% of subjects. The proportion of subjects who suffered from acne decreased from 46.5% at study entry to 14.9% after 13 medication cycles. More than 50% of the subjects who had switched from another oral contraceptive (OC) pill stated that the tolerability of EE 0.03 mg/CMA 2 mg and their health-related well-being were much better or better after two cycles of EE 0.03 mg/CMA 2 mg than when they were taking their previous OC, and about 85% of the subjects assessed the tolerability of EE 0.03 mg/CMA 2 mg as very good or good during the study. CONCLUSION: These results re-affirmed the favourable ADR profile of the COC EE 0.03 mg/CMA 2 mg, as well as its good cycle control and beneficial effects on dysmenorrhoea, complaints typically occurring during the cycle, acne and well-being.