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1.
Reprod Domest Anim ; 57(1): 72-79, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34706118

ABSTRACT

Benign prostatic hyperplasia (BPH) may alter prostatic fluid biochemical composition causing reduced fertility. Osaterone acetate (OA) is an androgen receptor antagonist marketed for treatment of canine BPH. Little information exists on effects of OA administration on biochemical composition of canine prostatic fluid and its role on fertility. The aim of this research was to study biochemical composition of prostatic fluid and its role on semen quality in dogs with BPH undergoing treatment with OA. Eight intact, 5-11-year-old dogs with benign prostatic hyperplasia were treated orally with OA at a dose of 0.25-0.5 mg/kg once daily for seven days. Prostatic volume, semen evaluation and a biochemical analysis of prostatic fluid were performed on the day before treatment (D0), D60, D120, D180 and D240. A significant reduction (57% and 61%) of prostatic volume was observed at D60 and D120, respectively, and a significant reduction (20%) of normal spermatozoa was observed at D60 coincident with a significant increase of sperm tail defects, which disappeared during the course of the treatment. Prostatic fluid composition did not vary during the OA treatment except for zinc (Zn2+ ) with a significant increase at D120 and D180 correlated with the return to normal sperm values. In conclusion, canine Zn2+ prostatic fluid concentrations decrease during development of BPH and return to normal during treatment with OA. Zn2+ is an important electrolyte for semen quality, suggesting that oral Zn2+ supplementation might be considered a treatment to improve semen quality.


Subject(s)
Dog Diseases , Prostatic Hyperplasia , Animals , Chlormadinone Acetate/analogs & derivatives , Dog Diseases/drug therapy , Dogs , Male , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/veterinary , Semen Analysis/veterinary
2.
Eur J Contracept Reprod Health Care ; 25(1): 43-48, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31756117

ABSTRACT

Objectives: The aim of this study was to compare changes in body weight in women using a combined oral contraceptive (COC) consisting of 30-µg ethinylestradiol (EE) and 2-mg chlormadinone acetate (CMA) or a COC consisting of 30-µg EE and 3-mg drospirenone (DRSP).Methods: This randomised double-blind controlled trial (ClinicalTrials.gov NCT01608698) was conducted at a university hospital-based clinic in Thailand between June 2012 and September 2015. A total of 102 women were enrolled in the study, 99 of whom were randomised to EE/CMA (n = 45) or EE/DRSP (n = 54). Each participant was treated for six cycles. Body weight and other parameters as well as side effects were recorded at baseline and at the end of the third and sixth cycles of treatment.Results: A significant difference was observed in mean body weight change between the EE/CMA and EE/DRSP groups from both baseline to third cycle (0.51 ± 1.36 kg vs -0.43 ± 1.56 kg; p = .003) and baseline to sixth cycle (1.00 ± 1.84 kg vs -0.20 ± 2.23 kg; p = .013). The mean difference in body mass index and waist circumference had a similar trend to that of the mean difference in body weight. There was no significant difference in side effects between groups.Conclusion: A COC containing 30-µg EE/3-mg DRSP tended to confer a significantly more favourable change in body weight over a 6-month period compared with a COC containing 30-µg EE/2-mg CMA, which was associated with an increase in body weight.


Subject(s)
Androstenes/adverse effects , Body Weight/drug effects , Chlormadinone Acetate/analogs & derivatives , Contraceptives, Oral, Combined/adverse effects , Ethinyl Estradiol/analogs & derivatives , Weight Gain/drug effects , Adolescent , Adult , Body Mass Index , Chlormadinone Acetate/adverse effects , Double-Blind Method , Ethinyl Estradiol/adverse effects , Female , Humans , Young Adult
3.
Pol J Vet Sci ; 21(4): 559-566, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30605276

ABSTRACT

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.


Subject(s)
Androgen Antagonists/therapeutic use , Chlormadinone Acetate/analogs & derivatives , Dog Diseases/drug therapy , Prostatic Hyperplasia/veterinary , Animals , Chlormadinone Acetate/therapeutic use , Dogs , Male , Prostate/drug effects , Prostate/pathology , Prostatic Hyperplasia/drug therapy
4.
Schweiz Arch Tierheilkd ; 158(3): 193-7, 2016 Mar.
Article in German | MEDLINE | ID: mdl-27518315

ABSTRACT

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.


Subject(s)
Adrenal Insufficiency/veterinary , Chlormadinone Acetate/analogs & derivatives , Dog Diseases/chemically induced , Prostatic Hyperplasia/veterinary , Adrenal Insufficiency/chemically induced , Adrenal Insufficiency/diagnosis , Animals , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/therapeutic use , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dogs , Glucocorticoids/therapeutic use , Male , Prednisolone/therapeutic use , Prostatic Hyperplasia/drug therapy , Treatment Outcome
5.
J Zoo Wildl Med ; 47(2): 609-13, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27468035

ABSTRACT

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.


Subject(s)
Chlormadinone Acetate/analogs & derivatives , Monkey Diseases/diagnosis , Prostatic Hyperplasia/veterinary , Saguinus , Androgen Antagonists/therapeutic use , Animals , Chlormadinone Acetate/therapeutic use , Male , Monkey Diseases/therapy , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/therapy
6.
Gen Hosp Psychiatry ; 36(2): 230.e1-2, 2014.
Article in English | MEDLINE | ID: mdl-24287129

ABSTRACT

OBJECTIVE: Female sexual hormones (estrogens and gestagens) may affect neurocognitive functioning and mood. Thus, the use of oral hormonal contraceptives (OHC) bears the risk of psychiatric adverse drug reactions such as depression and psychosis. However, the available empiric evidence regarding this connection is conflicting, and, moreover, female sex hormones seem to feature also mood-stabilizing and antidepressive effects. Hence, individual susceptibility factors and preparation-specific pharmacologic properties might play a pivotal role in the development of mood disturbances related to OHC. Single case reports provide empiric data for further systematic approaches. METHODS: A clinical case is presented and discussed. RESULTS: A 36-year-old female patient with recurrent major depressive disorder developed rapid relapse in depression after initialization of OHC with ethinyl estradiol 30 µg/chlormadinone acetate 2 mg. This OHC combination was described to particularly feature positive effects on depressive mood. CONCLUSIONS: OHC may induce serious mood disturbances and should be administered with care, particularly in patients with affective disorders.


Subject(s)
Chlormadinone Acetate/analogs & derivatives , Contraceptives, Oral, Combined/adverse effects , Depressive Disorder, Major/chemically induced , Ethinyl Estradiol/analogs & derivatives , Adult , Chlormadinone Acetate/adverse effects , Ethinyl Estradiol/adverse effects , Female , Humans , Recurrence
7.
Contraception ; 86(3): 268-75, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22464410

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/physiopathology , Chlormadinone Acetate/analogs & derivatives , Contraceptives, Oral, Combined/therapeutic use , Ethinyl Estradiol/analogs & derivatives , Mineralocorticoid Receptor Antagonists/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Spironolactone/therapeutic use , Adult , Blood Glucose , Body Mass Index , C-Reactive Protein/analysis , Cardiovascular Diseases/blood , Carotid Arteries/diagnostic imaging , Carotid Intima-Media Thickness , Chlormadinone Acetate/therapeutic use , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Drug Therapy, Combination , Ethinyl Estradiol/therapeutic use , Female , Humans , Insulin/blood , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/physiopathology , Risk Factors , Sex Hormone-Binding Globulin/analysis , Testosterone/blood , Triglycerides/analysis , Vasodilation
8.
Contraception ; 86(4): 359-65, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22445436

ABSTRACT

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.


Subject(s)
Androgen Antagonists/therapeutic use , Chlormadinone Acetate/analogs & derivatives , Drugs, Generic/therapeutic use , Dysmenorrhea/drug therapy , Estrogens/therapeutic use , Ethinyl Estradiol/analogs & derivatives , Virilism/drug therapy , Adult , Androgen Antagonists/adverse effects , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/therapeutic use , Contraceptives, Oral, Combined/adverse effects , Contraceptives, Oral, Combined/therapeutic use , Drug Combinations , Drugs, Generic/adverse effects , Dysmenorrhea/physiopathology , Estrogens/adverse effects , Ethinyl Estradiol/adverse effects , Ethinyl Estradiol/therapeutic use , Female , Hair Diseases/etiology , Hair Diseases/prevention & control , Humans , Menstrual Cycle/drug effects , Patient Dropouts , Pelvic Pain/etiology , Pelvic Pain/prevention & control , Product Surveillance, Postmarketing , Progestins/adverse effects , Progestins/therapeutic use , Prospective Studies , Severity of Illness Index , Skin Diseases/etiology , Skin Diseases/prevention & control , Virilism/physiopathology , Young Adult
9.
Contraception ; 84(4): 390-401, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21920195

ABSTRACT

BACKGROUND: The study was conducted to assess the contraceptive efficacy, cycle events, dysmenorrhea symptoms and skin complaints of a combined oral contraceptive containing 2 mg chlormadinone acetate/0.03 mg ethinylestradiol (CMA/EE) (Belara®, Grünenthal GmbH, Aachen, Germany) in adolescent and adult women using a conventional- or extended-cycle regimen. STUDY DESIGN: Data were pooled from six noninterventional trials with CMA/EE intake over 4-12 cycles. RESULTS: The data pool contained 62,218 women (345,964 cycles), of whom 60,508 were analyzed (325,937.5 cycles), including 46,335 adults, 13,478 adolescents and 695 age unknown; 1710 retrospective documented patients were excluded from analysis. A total of 85 women became pregnant (including women missing pills) on the conventional-cycle regimen (21+7), giving a practical Pearl index of 0.34 [95% confidence interval (CI) 0.27-0.42]. Within this group (n=85), there were 19 pregnancies associated with regular pill intake, which represent a theoretical Pearl index of 0.08 (95% CI 0.05-0.12) per 100 women-years. Overall, cycle stability, bleeding profile, dysmenorrhea and the incidence of seborrhea/acne improved with CMA/EE, and there was no clinically relevant change in body weight or body mass index. Six venous thromboembolic events were reported, equating to an incidence of 2.4 per 10,000 women-years. CONCLUSIONS: Chlormadinone acetate/ethinylestradiol is effective and well tolerated in adolescent and adult women.


Subject(s)
Chlormadinone Acetate/analogs & derivatives , Contraceptives, Oral, Combined/administration & dosage , Ethinyl Estradiol/analogs & derivatives , Acne Vulgaris/drug therapy , Adolescent , Adult , Chlormadinone Acetate/administration & dosage , Chlormadinone Acetate/adverse effects , Clinical Trials as Topic , Contraceptives, Oral, Combined/adverse effects , Dysmenorrhea/drug therapy , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/adverse effects , Female , Germany , Humans , Menstrual Cycle , Venous Thrombosis/chemically induced , Young Adult
11.
Am J Clin Dermatol ; 12 Suppl 1: 3-11, 2011 Sep 06.
Article in English | MEDLINE | ID: mdl-21895044

ABSTRACT

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.


Subject(s)
Androgens/metabolism , Chlormadinone Acetate/analogs & derivatives , Ethinyl Estradiol/analogs & derivatives , Skin Diseases/drug therapy , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/pharmacology , Chlormadinone Acetate/therapeutic use , Contraceptives, Oral, Combined/adverse effects , Contraceptives, Oral, Combined/pharmacology , Contraceptives, Oral, Combined/therapeutic use , Ethinyl Estradiol/adverse effects , Ethinyl Estradiol/pharmacology , Ethinyl Estradiol/therapeutic use , Female , Hair Follicle/metabolism , Humans , Quality of Life , Sebaceous Glands/metabolism , Skin Diseases/physiopathology
12.
Am J Clin Dermatol ; 12 Suppl 1: 13-9, 2011 Sep 06.
Article in English | MEDLINE | ID: mdl-21895045

ABSTRACT

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.


Subject(s)
Androgens/metabolism , Chlormadinone Acetate/analogs & derivatives , Ethinyl Estradiol/analogs & derivatives , Skin Diseases/drug therapy , Adult , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/therapeutic use , Contraceptives, Oral, Combined/adverse effects , Contraceptives, Oral, Combined/therapeutic use , Ethinyl Estradiol/adverse effects , Ethinyl Estradiol/therapeutic use , Female , Humans , Skin Diseases/diagnosis , Skin Diseases/physiopathology , Treatment Outcome , Young Adult
13.
Clin Drug Investig ; 31(4): 269-77, 2011.
Article in English | MEDLINE | ID: mdl-21250761

ABSTRACT

BACKGROUND AND OBJECTIVE: The prescribing of extended regimens of oral contraceptives (OCs) is increasing in routine gynaecological practice as a means of reducing the number of annual menstrual bleeds. Typically, this involves taking one pill per day for, say, 84 days continuously (4×21 days), followed by a 7-day pill-free interval. Low-dose OCs are suitable for extended use, and many gynaecologists in Germany prescribe the combination of chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg (CMA 2 mg/EE 0.03 mg). The aim of the current study was to assess the risks and benefits of CMA 2 mg/EE 0.03 mg in extended regimens, using pooled data from observational studies. METHODS: This pooled analysis of three large-scale, non-interventional, observational studies assessed the results in women receiving Belara® (CMA 2 mg/EE 0.03 mg) according to an extended regimen compared with conventional regimens documented in the summary of product characteristics. RESULTS: A total of 625 women were identified as extended-regimen users (mean±SD age 24.9±9.0 years). Extended-cycle use was associated with decreases in skin problems, dysmenorrhoea symptoms (as shown by reductions in analgesic use; absence from school, university, or work; and restrictions in leisure and sporting activities), cycle-dependent symptoms (e.g. headache/migraine, breast tenderness), withdrawal bleeding, bleeding duration and reduced libido. Mean bodyweight remained almost constant over 6 months. Only nine adverse drug reactions, none severe, were reported in eight women (1.3%). CONCLUSION: This pooled analysis confirms that extended regimens of CMA 2 mg/EE 0.03 mg reduce cycle-related complaints and are very well tolerated.


Subject(s)
Chlormadinone Acetate/analogs & derivatives , Contraceptives, Oral, Combined/pharmacology , Ethinyl Estradiol/analogs & derivatives , Menstrual Cycle/drug effects , Administration, Oral , Adult , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/pharmacology , Contraceptives, Oral, Combined/adverse effects , Ethinyl Estradiol/adverse effects , Ethinyl Estradiol/pharmacology , Female , Humans
14.
Reprod Sci ; 17(8): 767-75, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20595709

ABSTRACT

This is the first study evaluating the clinical, metabolic, and hormonal effects of the ethinylestradiol-chlormadinone acetate (EECMA) combination in hirsute women with polycystic ovary syndrome (PCOS). Ultrasonographic pelvic examination, hirsutism score, and hormone profile evaluation were performed at baseline and after 3 and 6 cycles of treatment. Oral glucose tolerance test, euglycemic-hyperinsulinemic clamp, and assessment of lipid profile were carried out at baseline and after 6 cycles of treatment. A significant improvement in hirsutism was evident at the end of treatment. From the third cycle onward, plasma levels of sex hormone binding globulin significantly increased when compared to baseline. Free androgen index, androstenedione, and 17-hydroxyprogesterone significantly decreased after 6 cycles. The treatment did not affect glucose and insulin homeostasis. Total cholesterol, triglycerides, and high-density lipoprotein (HDL) plasma levels remained unvaried, whereas low-density lipoprotein (LDL) concentrations showed a significant reduction. A significant increase in very-low-density lipoprotein (VLDL) levels was seen at the sixth cycle of therapy. In conclusion, EE-CMA combination ameliorates clinical and hormonal features of PCOS women, with no detrimental effects on glucose, insulin, and lipid metabolism.


Subject(s)
Chlormadinone Acetate/analogs & derivatives , Contraceptives, Oral, Combined/therapeutic use , Ethinyl Estradiol/analogs & derivatives , Hirsutism/drug therapy , Polycystic Ovary Syndrome/physiopathology , Adolescent , Adult , Blood Glucose/analysis , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/therapeutic use , Contraceptives, Oral, Combined/adverse effects , Ethinyl Estradiol/adverse effects , Ethinyl Estradiol/therapeutic use , Female , Glucose Clamp Technique , Glucose Tolerance Test , Hirsutism/blood , Humans , Lipids/blood , Polycystic Ovary Syndrome/blood , Young Adult
15.
Contraception ; 81(5): 391-400, 2010 May.
Article in English | MEDLINE | ID: mdl-20399945

ABSTRACT

OBJECTIVE: The study was conducted to compare the effects of 0.02 mg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA), given for 24 days each cycle, with those of 0.02 mg EE/0.15 mg desogestrel (DSG) and 0.03 mg EE/0.15 mg levonorgestrel (LNG), given for 21 days each cycle, on hemostatic, lipid, and carbohydrate metabolism parameters in healthy subjects, over six medication cycles. STUDY DESIGN: A randomized, multicentre, open-label, Phase II trial measured markers of hemostasis, and of lipid and carbohydrate metabolism in 165 subjects randomly assigned to treatment with one of three combined oral contraceptives (COCs). RESULTS: EE/CMA and EE/DSG had a similar effect on hemostatic parameters, the EE/LNG group showed comparatively smaller increases in the activity of factor VII [8.1% vs. 36.6% (EE/CMA) and 28.2% (EE/DSG)], protein C [5.9% vs. 32.9% (EE/CMA) and 21% (EE/DSG)] and endogenous thrombin potential-based activated protein C resistance [44.1% vs. 93.5% (EE/CMA) and 108.1% (EE/DSG)], and in contrast, free protein S levels decreased in the EE/CMA and EE/DSG groups (-12.7% and -4.3%, respectively) but rose in the EE/LNG group (20.4%). In all treatments, total cholesterol, total triglyceride and apolipoproteins increased. Levels of very low-density lipoprotein cholesterol particularly rose across all groups. Slight increases in high-density lipoprotein (HDL) cholesterol were observed for EE/CMA (14.6%) and EE/DSG (8.5%), with a rise above the upper limit of normal in 30% of the subjects taking EE/CMA. Conversely, for EE/LNG slight decreases in HDL cholesterol were observed (-12.4%) lipoprotein (a) levels decreased in the EE/CMA (-6.6%) and EE/LNG (-16.9%) groups and were unchanged in the EE/DSG group. CONCLUSIONS: The changes observed were typical of those seen across low-dose COCs that differ according to commonly-used progestogens.


Subject(s)
Carbohydrate Metabolism/drug effects , Chlormadinone Acetate/analogs & derivatives , Contraceptives, Oral, Combined/pharmacology , Ethinyl Estradiol/analogs & derivatives , Hemostasis/drug effects , Lipid Metabolism/drug effects , Adolescent , Adult , Chlormadinone Acetate/pharmacology , Desogestrel/pharmacology , Drug Combinations , Ethinyl Estradiol/pharmacology , Female , Humans , Levonorgestrel/pharmacology , Young Adult
16.
Contraception ; 79(1): 15-23, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19041436

ABSTRACT

BACKGROUND: This study was conducted to compare the effects of two monophasic oral contraceptives (OCs) containing ethinyl estradiol (EE) 30 mcg+either chlormadinone acetate (CMA) 2 mg (Belara) or 0.15 mg desogestrel (Marvelon) on lipid, hormone and other relevant metabolic parameters. STUDY DESIGN: Markers of lipid and carbohydrate metabolism, and reproductive hormone levels, were measured in 45 subjects randomly assigned to 6 months of treatment with one of the two OCs. The cortisol response to adrenocorticotrophic hormone (ACTH) stimulation was also evaluated. RESULTS: In both treatment groups, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and Apo AII levels increased; low-density lipoprotein cholesterol (LDL-C) and the LDL-C/HDL-C ratio decreased; and total cholesterol and lipoprotein(a) were unchanged during treatment. Effects on HDL-C, Apo AI, LDL-C and the LDL-C/HDL-C ratio were more evident in the EE 30 mcg+CMA 2 mg group. Follicle-stimulating hormone, luteinizing hormone and androgen levels decreased and sex hormone-binding globulin levels increased in both groups. Both OCs increased basal cortisol levels and cortisol response to ACTH. Oral contraceptive did not have a clinically significant impact on carbohydrate metabolism. CONCLUSIONS: Both low-dose monophasic OCs had comparable effects on lipid, hormone and metabolic parameters during six cycles of treatment in healthy female subjects. There was some evidence of a beneficial effect on atherogenic cardiovascular risk markers, which was slightly more pronounced with EE 30 mcg+CMA 2 mg.


Subject(s)
Carbohydrate Metabolism/drug effects , Contraceptives, Oral, Combined/pharmacology , Hydrocortisone/blood , Lipid Metabolism/drug effects , Lipids/blood , Adolescent , Adult , Apolipoproteins/analysis , Chlormadinone Acetate/analogs & derivatives , Chlormadinone Acetate/pharmacology , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Contraceptives, Oral, Hormonal , Desogestrel/pharmacology , Ethinyl Estradiol/pharmacology , Female , Humans , Lipoproteins/blood , Phospholipids/blood , Single-Blind Method , Triglycerides/blood , Young Adult
17.
Vet Rec ; 163(6): 179-83, 2008 Aug 09.
Article in English | MEDLINE | ID: mdl-18689779

ABSTRACT

A multicentre randomised clinical trial was performed to compare the therapeutic potential of osaterone acetate with that of delmadinone acetate in the treatment of benign prostatic hyperplasia in dogs. The osaterone was administered orally at 0.25 mg/kg bodyweight once a day for seven days to 73 dogs. The delmadinone was administered by a single intramuscular or subcutaneous injection at 3 mg/kg bodyweight to 69 dogs. During the 180-day trial, the dogs were monitored five times for their clinical signs and prostate volume. The two drugs were similarly effective in reducing the clinical signs and inducing complete clinical remission, and both induced a similar level of minor, mostly transitory adverse effects. Osaterone reduced the volume of the prostate glands of the dogs significantly more quickly than delmadinone.


Subject(s)
Androgen Antagonists/therapeutic use , Chlormadinone Acetate/analogs & derivatives , Dog Diseases/drug therapy , Prostatic Hyperplasia/veterinary , Androgen Antagonists/adverse effects , Animals , Chlormadinone Acetate/adverse effects , Chlormadinone Acetate/therapeutic use , Dogs , Drug Administration Schedule , Male , Prostatic Hyperplasia/drug therapy
18.
Steroids ; 70(9): 563-72, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15923016

ABSTRACT

Osaterone acetate (17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione; OA) is a steroidal antiandrogen. In order to clarify the species differences, metabolites of OA were examined in plasma, urine, and feces of dogs and humans after oral administration of OA. Eleven metabolites in plasma, urine, and feces were identified by their spectral properties and comparison to appropriate standards. The primary routes of OA metabolism involve 11 beta-, 15 beta- and 21-hydroxylation, 17 alpha-deacetylation, and dechlorination. Other metabolites arise from combinations of these pathways to form multiple oxidized metabolites. All metabolites observed in humans occurred in dogs. 11 beta-Hydroxylated metabolites (11 beta-OH OA and 11-oxo OA) were found in the plasma and urine of dogs, but there was no evidence of their presence in humans. 11 beta-Hydroxylation of exogenous steroids represents a distinctive biotransformation pathway.


Subject(s)
Chlormadinone Acetate/analogs & derivatives , Acetylation , Administration, Oral , Androgen Antagonists/blood , Androgen Antagonists/pharmacokinetics , Androgen Antagonists/urine , Animals , Chlormadinone Acetate/chemistry , Chlormadinone Acetate/metabolism , Chlormadinone Acetate/pharmacokinetics , Dogs , Feces/chemistry , Humans , Hydroxylation , Molecular Structure , Species Specificity , Steroids, Chlorinated/metabolism , Steroids, Chlorinated/pharmacokinetics
19.
Drugs ; 64(7): 751-60; discussion 761-2, 2004.
Article in English | MEDLINE | ID: mdl-15025547

ABSTRACT

Ethinylestradiol/chlormadinone acetate 0.03/2mg (EE/CMA) is a combined monophasic contraceptive pill with antiandrogenic properties. In a large, noncomparative, multicentre trial (< or =24 cycles of treatment per woman) and two (6- and 12-cycle) postmarketing surveillance studies, EE/CMA was effective in preventing pregnancy. EE/CMA was significantly more effective than EE/levonorgestrel 0.03/0.15 mg/day in treating women with mild-to-moderate papulopustular acne of the face and related disorders in a randomised, single-blind, multicentre trial. EE/CMA was well tolerated in clinical trials and the postmarketing surveillance studies. Adverse events were those commonly reported with oral contraceptives. As expected, the most common menstrual disturbances were breakthrough bleeding, spotting and amenorrhoea.


Subject(s)
Chlormadinone Acetate/therapeutic use , Contraceptives, Oral, Combined/therapeutic use , Drug Therapy, Combination , Ethinyl Estradiol/therapeutic use , Pituitary Diseases/drug therapy , Chlormadinone Acetate/analogs & derivatives , Clinical Trials, Phase III as Topic , Contraceptives, Oral, Combined/pharmacokinetics , Contraceptives, Oral, Combined/pharmacology , Controlled Clinical Trials as Topic , Endometrium/drug effects , Ethinyl Estradiol/analogs & derivatives , Fallopian Tubes/drug effects , Fallopian Tubes/physiology , Female , Germany , Humans
20.
Schweiz Arch Tierheilkd ; 145(3): 130-6, 2003 Mar.
Article in German | MEDLINE | ID: mdl-12677773

ABSTRACT

Three cases of fibroepithelial hyperplasia (FEH) of the mammary gland in the cat are reported. A one year old female cat had a distinct enlargement of the middle mammary glands, one on each side, 5 days after the first estrus. One week later the cat was treated with medroxyprogesterone acetate (Depo-Promone). The affected glands, along with the remaining glands, increased further in size. A five year old female cat was treated with Proligeston (Covinan) for the suppression of estrus. Two weeks later fibroepithelial hyperplasia occurred in two glands, one with a well demarcated ulceration. A seven months old male cat was treated with delmadinon acetate (Tarden) because of urine spraying. Two months later he had enlargement of all mammary glands. All three cats were treated with the progesterone antagonist Aglépristone (Alizine). Within 5 to 11 weeks the mammary glands had regressed to normal.


Subject(s)
Cat Diseases/drug therapy , Chlormadinone Acetate/analogs & derivatives , Estrenes/therapeutic use , Mammary Glands, Animal/pathology , Progesterone Congeners/adverse effects , Progesterone/analogs & derivatives , Progesterone/antagonists & inhibitors , Animals , Cat Diseases/chemically induced , Cats , Chlormadinone Acetate/adverse effects , Female , Hyperplasia/chemically induced , Hyperplasia/drug therapy , Hyperplasia/veterinary , Male , Mammary Glands, Animal/drug effects , Medroxyprogesterone Acetate/adverse effects , Progesterone/adverse effects , Treatment Outcome
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