1.  Title: Activation of NF-kappaB and COX-2 expression is associated with breakthrough bleeding in patients using oral contraceptives in extended regimens. Author: Maia H Jr; Casoy J; Correia T; Athayde C; Valente J; Coutinho EM Source: Gynecological Endocrinology. 2009 Sep 11;:1-5. Abstract: The objective of the present study was to determine whether there is an increase in endometrial inflammation associated with the occurrence of breakthrough bleeding in patients using an oral contraceptive in extended regimens. The presence of nuclear factor NF-kappaB and Cox-2 expression was determined by immunohistochemistry in endometrial samples removed by hysteroscopy from patients with breakthrough bleeding during continuous use of an oral contraceptive containing gestodene. All patients had a history of menorrhagia associated or not with the presence of uterine pathology. The percentage of endometria showing a positive staining reaction for NF-kappaB in cell nuclei was significantly higher in patients with breakthrough bleeding than in those with amenorrhea. Cox-2 expression in the endometrium was also significantly more frequent in patients with breakthrough bleeding. The occurrence of breakthrough bleeding in patients with uterine pathology using combined oral contraceptives is associated with the activation of endometrial inflammation through the NF-kappaB pathway. Language: English Keywords: BRAZIL | RESEARCH REPORT | CLIENTS | ORAL CONTRACEPTIVES, COMBINED | ENDOMETRIAL EFFECTS | MENORRHAGIA | ETHINYL ESTRADIOL | GESTODENE | AMENORRHEA | HISTOLOGY | South America, Eastern | South America | Latin America | Americas | Developing Countries | Program Activities | Programs | Organization and Administration | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Endometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | Menstruation Disorders | Diseases | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin Document Number: 342842 |
| 2. Title: The Transnational study of oral contraceptive cardiovascular safety: history and science. Author: Suissa S Source: Journal of Clinical Epidemiology. 2009;62:588-593. Abstract: This study, in which Kuhl et al. reported elevated ethinyl estradiol (EE) levels in women receiving the gestodene/EE combination oral contraceptives (OCs) compared with desogestrel-containing combination OCs, by its implication that such differences could be associated with increased cardiovascular risks, had attracted much publicity and created great concern in Germany. The working group found sufficient methodological deficiencies in the Kuhl study to question the validity of its findings of significant differences in effects between the various OCs. Besides a large number of studies mostly irrelevant to the issue of cardiovascular risk, Schering had conducted a large postmarketing phase IV study in over 100,000 women. Joe Fleiss, who was the primary reviewer of that report, presented the shortest review I had ever witnessed: he raised the thick report in the air and simply tossed it on the floor. It was clear to all that the data were simply unreliable and unusable to address this safety concern. The working group thus recommended that the only way to address the safety issue regarding gestodene was to conduct epidemiological studies on the safety of all newer low-dose OCs and saw it as an international priority, particularly in view of the number of newer OCs that had been brought to market and the scarcity of recent published studies. Schering agreed in principle to fund such research, and Walter coordinated the writing of protocols for a research program that included three studies. The Trinational study, a field case-control study conducted in three European countries was the only one retained. The Value Added Medical Products (VAMP), the predecessor of the General Practice Research Database (GPRD), historical cohort study was rejected for political (no data on German women) and scientific reasons, such as the absence of important confounder data and insufficient OC history. The Saskatchewan study was rejected because gestodene was not available in Saskatchewan, and other low-dose COCs, by themselves, were not relevant to the sponsors. (excerpt) Language: English Keywords: EUROPE, WESTERN | CONFERENCES AND CONGRESSES | CLINICAL RESEARCH | EPIDEMIOLOGIC METHODS | CROSS-CULTURAL COMPARISONS | WOMEN | CONTRACEPTIVE SAFETY | ORAL CONTRACEPTIVES | CARDIOVASCULAR EFFECTS | GESTODENE | ORAL CONTRACEPTIVES, COMBINED | DESOGESTREL | ORAL CONTRACEPTIVES, LOW-DOSE | LOW-DOSE PROGESTINS | NORTH AMERICA, NORTHERN | Europe | Developed Countries | Research Methodology | Comparative Studies | Studies | Demographic Factors | Population | Safety | Public Health | Health | Contraceptive Methods | Contraception | Family Planning | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Americas Document Number: 331005 |
| 3. Peer Reviewed Title: Effects of two combined oral contraceptives containing ethinyl estradiol 30 mug combined with either gestodene or drospirenone on hemostatic parameters, lipid profiles and blood pressure. Author: Yildizhan R; Yildizhan B; Adali E; Yoruk P; Birol F Source: Archives of Gynecology and Obstetrics. 2009 Jan 6;:[7] p. Abstract: OBJECTIVE: The aim of this study is to compare the effect of ethinyl estradiol 0.03 mg/gestodene 0.075 mg (EE/GSD) with ethinylestradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) administered according to conventional 21/7 regimen on body mass index (BMI), blood pressure (BP), lipid metabolism and hemostatic parameters. METHOD: In this study, 160 healthy women were randomized to EE/GSD mg or EE/DRSP for 12 months. Mean differences in BMI, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) levels and BP compared to baseline were assessed. RESULTS: One hundred and forty-five (89%) of the women completed all 12 treatment cycles. The subjects randomly assigned into two treatment groups. Group EE/GSD (n = 71) and group EE/DRSP (n = 72). In group B, BMI values were significantly lower than baseline at the sixth cycle. DRSP/EE had more favorable effects on BP than GSD/EE with the mean systolic and diastolic BPs remaining lower in the DRSP/EE group. The difference between the two preparations was not statistically significant at the end of the study. TC levels remained similar in both groups throughout the study period. In both groups LDL-C levels decreased, triglyceride and HDL-C levels significantly increased from baseline levels. These changes result in increasing HDL-C/LDL-C ratio, demonstrating anti-atherogenic effect. Menstrual cycle patterns and the incidence of adverse events were similar between groups. The duration of withdrawal bleeding decreased during the study for both groups and was similar. CONCLUSION: The EE/DRSP regimen provides good cycle control with reliable contraceptive efficacy and low incidence of adverse events. Compared with the EE/GSD preparation, the EE/DRSP preparation demonstrated a more favorable effect on BMI and BP with the mean BMI and mean BP remaining lower than baseline mean. The new formulation may be especially beneficial for women susceptible to body weight gain and rise in BP. Language: English Keywords: GERMANY | RESEARCH REPORT | LABORATORY PROCEDURES | WOMEN | ORAL CONTRACEPTIVES | ETHINYL ESTRADIOL | CHOLESTEROL | GESTODENE | CONTRACEPTIVE SAFETY | BODY WEIGHT | Europe, Central | Europe | Developed Countries | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Lipids | Physiology | Biology | Contraceptive Agents, Progestin | Safety | Public Health Document Number: 329673 |
| 4. Title: Effect of two low-dose gestodene containing monophasic oral contraceptives on hemostasis in Bulgarian women. Author: Uchikova E; Pehlivanov B Source: Expert Opinion On Pharmacotherapy. 2008 Aug;9(11):1839-44. Abstract: OBJECTIVE: To compare the effects of two monophasic oral contraceptives upon coagulation, fibrinolysis and the system of natural inhibitors (anticoagulant pathways) in Bulgarian women. METHODS: This prospective, open clinical study lasted 12 months and included 70 women, divided into two equal groups of 35 each. The women from group A received a contraceptive containing 20 microg ethinylestradiol/75 microg gestodene. The women from group B received a contraceptive containing 30 microg ethinylestradio l/75 microg gestodene. At the beginning and again at the end of the study, the following values were determined: prothrombin time (PT), activated partial thromboplastic time (aPTT), thrombin time (TT), fibrinogen (F), Factor VII (FVII), Factor X (FX), plasminogen, alpha 2-antiplasmin, tissue-type plasminogen activator (t-PA), D-dimers, protein C (Pr C), total Protein S (TPr S), antithrombin III (AT III) and heparin Cofactor II (HC II). RESULTS: We did not find any statistically significant differences in the global tests of hemostasis (PT, aPTT, TT) in either group compared with the baseline values. At the end of the study there was an increase in the levels of fibrinogen, FX, PrC and H II, and also diminution of t-PA in both groups in comparison with the baseline values. At the end of the study the activity of FVII, alpha2-antiplasmin and AT III was elevated only in group B. Although certain alterations in hemostasis parameters were observed, all of them were within the reference range. We did not observe or suspect any cases of vascular, thrombotic or other incidence in the observed groups of 840 cycles of hormonal contraception over the 12-month period. CONCLUSION: There is an increase in both procoagulant and fibrinolytic activity when using low-dose gestodene containing monophasic oral contraceptives. This can be interpreted as a shift to a higher equilibrium. There is no need for screening for thrombofilia in healthy, non-obese, non-smoking Bulgarian females, aged between 18 to 35 years, without a personal or family history of thrombotic diseases, before starting on third generation oral contraceptive with gestodene. Language: English Keywords: BULGARIA | RESEARCH REPORT | COMPARATIVE STUDIES | WOMEN | CLIENTS | ETHINYL ESTRADIOL | GESTODENE | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, LOW-DOSE | ORAL CONTRACEPTIVES, SIDE EFFECTS | PROGRAM EFFECTIVENESS | Europe, Southeastern | Europe | Developing Countries | Studies | Research Methodology | Demographic Factors | Population | Program Activities | Programs | Organization and Administration | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Methods | Contraceptive Safety | Safety | Public Health | Health | Program Evaluation Document Number: 328306 |
| 5. Title: Research on the new one rod contraceptive implant containing gestodene. Author: Chen HL; Chen JX Source: Journal of Reproduction and Contraception. 2007 Jun;18(2):86-88. Abstract: The objective was to develop a new contraceptive implant containing gestodene featuring with only one rod for 5 years long effectiveness and safety. Gestodene synthesis, polymer tube designation, in vitro or in vivo test, the pilot test was used for the establishing of minimum clinic dosage. It had a burst effect at beginning and become constantly releasing since 12th day. It had zero-order releasing, in vitro, the average releasing rate was 17.0-19.1 µg/d, the safe dosage was 70.2mg/kg, C/1hr was 2.91 ± 1.25 ng/ml, T/max was 8.86 ± 4.32 h, C/max was 7.31 ± 1.09 ng/ml, T/ss was 14 d,Css was 4.16 ± 0.48 ng/ml. Twenty-four hours later after removal of the implant, gestodene was almost cleaned out in the blood circulation and only trace amount of drug was detected after the removal. One rod gestodene implant is a new long effective contraceptive and may be promising. (author's) Language: English Keywords: CHINA | RESEARCH REPORT | CLINICAL RESEARCH | WOMEN | CONTRACEPTIVE IMPLANTS | GESTODENE | ADMINISTRATION AND DOSAGE | SIDE EFFECTS | CONTRACEPTIVE EFFECTIVENESS | SAFETY | TOXICITY | Asia, Eastern | Asia | Developing Countries | Research Methodology | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Public Health | Physiology | Biology Document Number: 308493 |
| 6. Peer Reviewed Title: Prospective, open-label, noncomparative study to assess cycle control, safety and acceptability of a new oral contraceptive containing gestodene 60 micrograms ethinylestradiol 15 micrograms (Minesse). [Estudio prospectivo no comparativo de diseño abierto para evaluar el control del ciclo, la seguridad y la aceptabilidad de un nuevo anticonceptivo oral con 60 microgramos de gestodeno y 15 microgramos de etinilestradiol (Minesse)] Author: Barbosa IC; Filho CI; Faggion D Jr; Baracat EC Source: Contraception. 2006;73:30-33. Abstract: A prospective, open-label, noncomparative, multicenter study was carried out in 163 women aged 18-39 (mean 25 ± 5 years), who used an ultra-low-dose oral contraceptive pill (OCP) containing gestodene (GTD) 60 µg/ethinylestradiol (EE) 15 µg for 6 months. The objective of the study was to evaluate the acceptability, safety, bleeding patterns and premenstrual symptomatology in these women. Patients used the OCP from Days 1-24, followed by a 4-day pill-free interval from Days 25-28 of the menstrual cycle. Physical and gynecological examinations were carried out at baseline and after 3 and 6 months, at which time blood pressure, weight, hemoglobin, hematocrit, SGOT, SGPT and urinalysis were also assessed. The Moos Menstrual Distress Questionnaire (MDQ) was completed on three consecutive days (Days 25-27 of the cycle) at baseline and at the end of the third and sixth cycles. Patients kept a menstrual diary throughout the study. A total of 146 women completed the study. Ten women discontinued because of adverse events and one undesired pregnancy occurred during treatment. No adverse metabolic effects were observed. The adverse event most frequently reported was breakthrough bleeding, which diminished, however, as the time of OC use increased. Cycle length and duration of bleeding decreased significantly with OC use (p < .01 and p < .05, respectively, after 6 months). Intensity of menstrual bleeding tended to decrease with OC use, but this difference was not statistically significant. Systolic and diastolic blood pressure were significantly lower after 6 months of OC use compared to baseline (p < .02). No alterations were recorded in body weight or laboratory evaluations. Statistically significant changes were found both in the total MDQ score and in several of the factors evaluated, and patients showed a statistically significant improvement in well-being with respect to premenstrual complaints and symptoms. This OC regimen is safe, well-accepted and well-tolerated, affects menstrual patterns beneficially by reducing both the intensity and duration of bleeding, provides good cycle control and improves premenstrual symptomatology. (author's) Spanish Abstract: Se realizó un estudio multicéntrico prospectivo no comparativo de diseño abierto sobre 163 mujeres de 18 a 39 años (edad promedio 25 ± 5 años), que tomaron una píldora anticonceptiva oral (OCP, oral contraceptive pill) de dosis ultra mínima con 60 µg de gestodeno (GTD) y 15 µg de etinilestradiol (EE) durante 6 meses. El objetivo del estudio fue evaluar la aceptabilidad, la seguridad, los patrones de sangrado y la sintomatología premenstrual de las mujeres. Las pacientes tomaron la píldora anticonceptiva del día 1 al 24, y después dejaron de tomarla en un intervalo de 4 días, del día 25 al 28 del ciclo menstrual. Al comienzo del estudio y después de 3 y 6 meses se realizaron exámenes físicos, ginecológicos y de orina, y se controlaron la tensión arterial, el peso, la hemoglobina, el hematócrito y las transaminasas glutámica oxaloacética y glutámica pirúvica (TGO y TGP). Se completó el cuestionario de molestias menstruales (MDQ, Menstrual Distress Questionnaire) elaborado por Moos en tres días consecutivos (días 25 a 27 del ciclo) al inicio del estudio y al final del tercer y del sexto ciclos. En el transcurso del estudio las pacientes llevaron un diario. En total completaron el estudio 146 mujeres. Diez mujeres lo abandonaron por sufrir eventos adversos y hubo un embarazo no deseado durante el tratamiento. No se observaron efectos metabólicos adversos. El evento adverso más frecuente fue la metrorragia intercurrente, que mermó al prolongarse el tiempo de uso del anticonceptivo oral. Tanto la duración del ciclo como la del sangrado disminuyeron significativamente con el uso del anticonceptivo oral (p < 0,01 y p < 0,05, respectivamente, luego de 6 meses). Si bien la intensidad del sangrado menstrual tendió a decrecer con el uso del anticonceptivo oral esta diferencia no fue estadísticamente significativa. La tensión arterial sistólica y diastólica después de 6 meses de uso del anticonceptivo oral mostró valores significativamente menores que los iniciales (p < 0,02). No se registraron alteraciones en el peso corporal ni en las pruebas de laboratorio. Se observaron cambios estadísticamente significativos tanto en el puntaje del cuestionario MDQ como en varios de los factores evaluados y las pacientes presentaron una mejoría estadísticamente significativa de sus dolores y síntomas premenstruales. Esta pauta terapéutica de los anticonceptivos orales es segura, bien aceptada y bien tolerada, produce un efecto benéfico en los patrones menstruales, reduciendo tanto la intensidad como la duración del sangrado, proporciona un buen control del ciclo y mejora la sintomatología premenstrual. (del autor) Language: English Keywords: BRAZIL | RESEARCH REPORT | PROSPECTIVE STUDIES | CLINICAL RESEARCH | WOMEN IN DEVELOPMENT | ETHINYL ESTRADIOL | ORAL CONTRACEPTIVES, LOW-DOSE | GESTODENE | ORAL CONTRACEPTIVES, COMBINED | PREMENSTRUAL TENSION | CONTRACEPTIVE SAFETY | METRORRHAGIA | South America, Eastern | South America | Latin America | Americas | Developing Countries | Studies | Research Methodology | Economic Development | Economic Factors | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Oral Contraceptives | Contraceptive Methods | Contraceptive Agents, Progestin | Menstruation Disorders | Diseases | Safety | Public Health | Health | Bleeding | Signs and Symptoms Document Number: 293356 |
| 7. Peer Reviewed Title: Effects of two different oral contraceptives on total body water: a randomized study. [Efectos de dos anticonceptivos orales diferentes sobre el total de agua en el organismo: estudio aleatorizado] Author: Machado RB; Tachotti F; Cavenague G; Maia E Source: Contraception. 2006 Apr;73(4):344-347. Abstract: This open-label, randomized study evaluated the effect of two different oral contraceptives on body weight and composition during one cycle of treatment. Eighty women (mean age, 24.6 years) were randomized into three groups and given one of the following contraceptive methods: ethinylestradiol 15 µg/gestodene 60 µg (EE/GST, n = 25), ethinylestradiol 30 µg/drospirenone 3 mg (EE/DRS, n = 29) or male condom (control group, n = 26). Bioelectric impedance analysis (BIA) was carried out on the first, 10th and 21st days during the use of oral contraceptives or in the menstrual cycle (control group), and total body water (TBW), fat mass (FM) and fat-free mass (FFM) were measured. No significant variations in TBW, FM or FFM were observed in the three groups during the cycle. Intergroup analysis showed no differences in TBW or FM; however, users of EE/GST showed a statistically significant increase in FFM compared to the control group. The different doses of ethinylestradiol associated with gestodene or drospirenone showed no statistically significant effects on TBW or FM during one cycle of observation. (author's) Spanish Abstract: Este estudio aleatorizado de etiqueta abierta analizó el efecto de dos anticonceptivos orales diferentes sobre el peso y la composición corporal durante un ciclo de tratamiento. Se realizó una asignación aleatoria de 80 mujeres (edad promedio: 24,6 años) a tres grupos y se les asignó uno de los siguientes métodos anticonceptivos: 15 µg de etinilestradiol / 60 µg de gestodeno (EE/GST, n = 25), 30 µg de etinilestradiol/ 3 mg de drospirenona (EE/DRS, n = 29) o preservativo masculino (grupo control, n = 26). Se aplicó análisis por impedancia bioeléctrica (BIA, bioelectric impedance analysis) en el día 1, 10 y 21 durante el uso de anticonceptivos orales o en el ciclo menstrual (grupo control) para medir la cantidad total de agua en el organismo (TBW, total body water), la masa adiposa (FM, fat mass) y la masa libre de grasa (FFM, fat-free mass). No se observaron variaciones significativas en ninguno de los tres parámetros en los tres grupos durante el ciclo. El análisis intergrupal no mostró diferencias en el total de agua en el organismo ni en la masa adiposa; sin embargo, se observó un aumento significativo en la masa libre de grasa de las usuarias de EE/GST en comparación con el grupo control. Las diferentes dosis de etinilestradiol asociado con gestodeno o drospirenona no presentaron efectos estadísticamente significativos sobre el total de agua ni masa adiposa corporal durante un ciclo de observación. (del autor) Language: English Keywords: BRAZIL | RESEARCH REPORT | CONTROL GROUPS | WOMEN | FAMILY PLANNING ACCEPTORS | ORAL CONTRACEPTIVES, COMBINED | BODY WEIGHT | ANTHROPOMETRY | PHYSIOLOGY | ESTRADIOL | GESTODENE | South America, Eastern | South America | Latin America | Americas | Developing Countries | Research Methodology | Demographic Factors | Population | Family Planning Programs | Family Planning | Oral Contraceptives | Contraceptive Methods | Contraception | Biology | Measurement | Estrogens | Hormones | Endocrine System | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 298526 |
| 8. Title: Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis. Author: Maia H Jr; Casoy J; Correia T; Freitas L; Pimentel K Source: Gynecological Endocrinology. 2006 Oct;22(10):547-551. Abstract: The objectives were to determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle. This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n=25) and luteal (n=10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n=7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods. Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expressionwas negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle. Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase. (author's) Language: English Keywords: BRAZIL | RESEARCH REPORT | COHORT ANALYSIS | WOMEN | MENORRHAGIA | ORAL CONTRACEPTIVES | GESTODENE | MENSTRUATION DISORDERS | Developing Countries | South America, Eastern | South America | Latin America | Americas | Research Methodology | Demographic Factors | Population | Diseases | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 314536 |
| 9. Peer Reviewed Title: Different oral contraceptives and voice quality -- an observational study. Author: Amir O; Biron-Shental T; Tzenker O; Barer T Source: Contraception. 2005;71:348-352. Abstract: The classical literature on endocrine effect on voice considers oral contraceptives (OCs) as a risk factor for voice. However, recent studies revealed no adverse effect of new-generation OCs on voice. It was also suggested that OCs could improve specific voice characteristics via different mechanisms. The aim of the present study was to evaluate the effect of OCs on voices of women who use different formulations containing drospirenone (n = 10), desogestrel (n = 9) and gestodene (n = 10). Acoustic voice measures of the 29 women were evaluated twice during the menstrual cycle. Fundamental frequency, frequency as well as amplitude stability and noise characteristics were measured using a computerized voice analysis program. Results indicated that vocal stability and quality were similar in the three groups tested. Marginal differences were observed between the drospirenone group and the other two groups. This preliminary observational study indicates that although drospirenone was previously shown to reduce water retention, this effect was not found to directly influence voice characteristics of women who use OCs. (author's) Language: English Keywords: ISRAEL | RESEARCH REPORT | CLINICAL TRIALS | WOMEN | ORAL CONTRACEPTIVES | DESOGESTREL | GESTODENE | ADMINISTRATION AND DOSAGE | ENDOCRINE EFFECTS | RISK FACTORS | SENSORY EFFECTS | Middle East | Developed Countries | Clinical Research | Research Methodology | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Drugs | Treatment | Endocrine System | Physiology | Biology Document Number: 284464 |
| 10. Peer Reviewed Title: Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives. [Evaluación del perfil lipídico en adolescentes durante el uso a largo plazo de anticonceptivos hormonales orales] Author: Guazzelli CA; Lindsey PC; de Araújo FF; Barbieri M; Petta CA Source: Contraception. 2005;71:118-121. Abstract: The study evaluated the effects of the long-term use of a combined oral hormonal contraceptive containing 30 µg ethinyl estradiol and 75 µg gestodene in adolescents. Thirty-three volunteers, aged from 14 to 19 years, who used the oral contraceptive for three consecutive years, were studied. Evaluation of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides was made before use and after 1, 2 and 3 years. During the 3-year study period, total cholesterol, HDL-C, LDL-C and triglyceride levels were significantly higher than previous measurements, but average values did not exceed the normal range. Compared to the first year, the second- and third-year cholesterol, HDL-C, LDL-C and triglyceride levels were not significantly different. (author's) Spanish Abstract: El estudio evaluó los efectos del uso a largo plazo de anticonceptivos hormonales orales combinados con contenido de 30 µg de etinil-estradiol y 75 µg de gestodeno. Se estudiaron treinta y tres voluntarias de 14 a 19 años que emplearon el anticonceptivo oral durante tres años consecutivos. Previo a la administración, al año, a los dos y a los tres años se evaluaron colesterol total, colesterol de lipoproteínas de alta densidad (HDL-C, high-density lipoprotein cholesterol), colesterol de lipoproteínas de baja densidad (LDL-C, low-density lipoprotein cholesterol) y triglicéridos. Durante el período del estudio de 3 años, los niveles de colesterol total, colesterol de lipoproteínas de alta densidad, colesterol de lipoproteínas de baja densidad y triglicéridos fueron significativamente superiores a las mediciones previas, pero los valores promedio no superaron el rango normal. Los niveles de colesterol total, HDL-C, LDL-C y triglicéridos para el segundo y tercer años no difirieron significativamente de los valores registrados en el primer año. (del autor) Language: English Keywords: BRAZIL | RESEARCH REPORT | EVALUATION | ADOLESCENTS, FEMALE | ORAL CONTRACEPTIVES, COMBINED | ETHINYL ESTRADIOL | GESTODENE | LONGTERM EFFECTS | CHOLESTEROL | LIPIDS | RISK FACTORS | HEALTH | Developing Countries | South America, Eastern | South America | Latin America | Americas | Adolescents | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Time Factors | Population Dynamics | Physiology | Biology Document Number: 281343 |
| 11. Peer Reviewed Title: Sexual behavior of women taking low-dose oral contraceptive containing 15 micrograms ethinylestradiol / 60 micrograms gestodene. Author: Caruso S; Agnello C; Intelisano G; Farina M; Di Mari L Source: Contraception. 2004 Mar;69(3):237-240. Abstract: The objective of this prospective study was to assess the effects of a low-dose oral contraceptive (OC) containing 15 µg ethinylestradiol and 60 µg gestodene on sexuality. Forty-eight healthy volunteers (age range, 18–35 years), having regular menstrual cycles with ovulation, participated in the study. Sexual behavior was assessed using the self-administered Personal Experience Questionnaire, at baseline, and at 3, 6 and 9 months of pill use. Women reported decreased sexual desire (p < 0.005) and sexual activity (p < 0.05) at the 9th month of pill use, and diminished sexual arousal at the 3rd month of pill intake (p < 0.05), with respect to baseline. The frequency of orgasm did not change during OC use (p = NS). Moreover, sexual enjoyment was worse at the 3rd, 6th and 9th month with respect to baseline (p < 0.001). The low dose of ethinylestradiol could cause decreased vaginal lubrication, and diminished sexual arousal could be due to hypoandrogenism. Women may expect increased sexual performance when they take the pill, as compared to before starting contraception. Consequently, they could have an unexpected effect with pill use, though sexuality may remain the same. (author's) Language: English Keywords: ITALY | RESEARCH REPORT | PROSPECTIVE STUDIES | QUESTIONNAIRES | WOMEN | FERTILITY | ORAL CONTRACEPTIVES, COMBINED | SEX BEHAVIOR | ETHINYL ESTRADIOL | GESTODENE | LOW-DOSE PROGESTINS | Europe, Southern | Europe | Developed Countries | Studies | Research Methodology | Demographic Factors | Population | Population Dynamics | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Behavior | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin Document Number: 190616 |
| 12. Peer Reviewed Title: A prospective open-label study to evaluate the effects of the oral contraceptive Harmonet (gestodene 75/EE20) on body fat. [Estudio prospectivo de etiqueta abierta para evaluar los efectos del anticonceptivo oral Harmonet (gestoden 75/EE20) sobre la grasa corporal] Author: de Melo NR; Aldrighi JM; Faggion D Jr; Reyes VR; Souza JB Source: Contraception. 2004 Jul;70(1):65-71. Abstract: This open-label study evaluated the effects on body fat of the use of a low-dose oral contraceptive (gestodene 75/EE20) in a group of 61 women (OC-U group) as compared to a nonuser group (OC-N group) of 51 women who did not receive an oral contraceptive. Weight, body mass index (BMI), waist-over-hip ratio and body composition data, obtained by bioelectrical impedance [percentages of body fat (%FAT), water (%TBW) and lean mass (%FFM)], were assessed before and after six treatment cycles. Baseline OC-U group weight, BMI, %FAT, %TBW and %FFM did not differ from the OC-N group, either at baseline or at the end of the study, and did not significantly change within each group during the study. Also, there was no modification of fat distribution in either group. Among women in the OC-U group, there was a slight increase in total cholesterol levels and a trend towards higher triglycerides levels. No changes were detected in blood pressure. In conclusion, this low-dose oral contraceptive did not affect weight or body composition. Thus, our data suggest that gestodene 75/EE20 represents an appropriate OC choice and may enhance compliance of women who mistakenly believe that the use of oral contraceptives always leads to weight gain. (author's) Spanish Abstract: Este estudio de etiqueta abierta evaluó los efectos del uso de un anticonceptivo oral de baja dosis (gestoden 75/EE20) sobre la grasa corporal en un grupo de 61 usuarias (OC-U, oral contraceptive users) en comparación con un grupo de 51 no usuarias (OC-N, oral contraceptive non-users) que no recibieron el anticonceptivo. Se evaluaron el peso, el índice de masa corporal (IMC), la relación cintura-cadera (ICC) y los datos de composición corporal obtenidos mediante impedancia bioeléctrica (porcentajes de grasa corporal [% GC], agua corporal total [% ACT] y masa libre de grasa [% MLG]) antes y después de seis ciclos de tratamiento. Los valores iniciales de peso, IMC, % GC, % ACT y % MLG del grupo de usuarias del anticonceptivo oral no difirieron de los del grupo de no usuarias, ni al inicio ni al final del estudio, ni variaron significativamente dentro de cada grupo en el curso del mismo. Tampoco se modificó la distribución de la grasa en ninguno de los grupos. Entre las usuarias del anticonceptivo oral se registró un leve incremento en los niveles de colesterol total y una tendencia a mayores niveles de triglicéridos. No se detectaron cambios en la presión arterial. En conclusión, este anticonceptivo de baja dosis no afectó el peso ni la composición corporal. En consecuencia, nuestros datos sugieren que el gestoden 75/EE20 es una opción adecuada de anticonceptivo oral y puede infundir confianza a las mujeres que creen erróneamente que el uso de anticonceptivos orales provoca indefectiblemente un aumento de peso. (del autor) Language: English Keywords: BRAZIL | RESEARCH REPORT | PROSPECTIVE STUDIES | COMPARATIVE STUDIES | WOMEN | ORAL CONTRACEPTIVES, LOW-DOSE | GESTODENE | BODY WEIGHT | LIPIDS | ANTHROPOMETRY | EVALUATION | Developing Countries | South America, Eastern | South America | Latin America | Americas | Studies | Research Methodology | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Physiology | Biology | Measurement Document Number: 194562 |
| 13. Title: Comparative evaluation of androgen and progesterone receptor transcription selectivity indices of 19-nortestosterone-derived progestins. [Evaluación comparativa de índices selectivos sobre la trascripción de los receptores de progesterona y andrógeno en progestinas derivadas de la 19-nortestosterona] Author: García-Becerra R; Cooney AJ; Borja-Cacho E; Lemus AE; Pérez-Palacios G Source: Journal of Steroid Biochemistry and Molecular Biology. 2004 Jun;91(1-2):21-27. Abstract: Synthetic 19-nortestosterone-derived progestins show affinity for the androgen receptor (AR) and retain varying degrees of androgenic activity. In this study, AR- and progesterone receptor (PR)-dependent transcriptional activation induced by norethisterone (NET), levonorgestrel (LNG) and gestodene (GSD), and their 5a-reduced derivatives, including limited trypsin digestion of AR in the presence of natural and synthetic progestins were investigated. The results confirmed the progestogenic activity of the three 19-nortestosterone derivatives, which decreases after reduction of the 4-ene-double bound. These compounds were able to activate AR-dependent reporter gene expression, LNG and GSD being the stronger activators. 5a-Reduction of LNG and GSD did not change their androgenic transcriptional activity; however, the activation of AR by 5a- NET was four-fold higher than NET. The highest selectivity transcriptional index as a measure of progestogenicity versus androgenicity, was obtained for NET. The 5a-reduced derivatives had values significantly lower than those of their parent compounds. Non-reduced and 5a-reduced 19-nortestosterone progestins induced virtually identical proteolysis fragmentation patterns of the AR to those observed with DHT. (author's) Spanish Abstract: Las progestinas derivadas de la 19-nortestosterona muestran afinidad con el receptor de andrógeno (AR, androgen receptor) y retienen en grados variados la actividad androgénica. En este estudio se investigó la activación transcripcional dependiente del AR y del receptor de progesterona (PR, progesterone receptor), inducida por noretisterona (NET, norethisterone), levonorgestrel (LNG) y gestodeno (GSD, gestodene), y sus derivados reducidos 5a, como la digestión del AR limitada de tripsina en presencia de progestinas sintéticas y naturales. Los resultados confirmaron la actividad progestagénica en los tres derivados de 19-nortestosterona, que disminuyen luego de la reducción de la doble ligadura 4-eno. Estos compuestos fueron capaces de activar la expresión del gen indicador AR dependiente, LNG y GSD como los activadores más fuertes. La reducción 5a de LNG y GSD no cambió su actividad transcripcional androgénica, sin embargo, la activación del AR mediante 5a- NET fue cuatro veces más alta que NET. El mayor índice transcripcional de selectividad, como medida de actividad progestogenicidad versus androgenicidad, se obtuvo para NET. Los derivados reducidos 5a tuvieron valores significativamente inferiores que los de sus compuestos de origen. Las progestinas de la 19-nortestosterona no reducida y reducida 5a indujeron virtualmente a idénticos patrones de fragmentación de proteólisis del AR que los observados con DHT. (del autor) Language: English Keywords: MEXICO | RESEARCH REPORT | LEVONORGESTREL | GESTODENE | ORAL CONTRACEPTIVES | ANDROGENS | PROGESTERONE | PROTEINS | METABOLIC EFFECTS | SIDE EFFECTS | North America | Latin America | Americas | Developing Countries | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Methods | Hormones | Endocrine System | Physiology | Biology | Progestational Hormones | Treatment Document Number: 277660 |
| 14. Peer Reviewed Title: Combined ethinylestradiol/gestodene contraceptive patch: two-center, open-label study of ovulation inhibition, acceptability and safety over two cycles in female volunteers. Author: Heger-Mahn D; Warlimont C; Faustmann T; Gerlinger C; Klipping C Source: European Journal of Contraception and Reproductive Health Care. 2004;9:173-181. Abstract: Determination of the ovulation inhibition efficacy of a new, transparent, transdermal, combined hormonal contraceptive patch (area 10 cm/2) containing 0.9 mg ethinylestradiol and 1.9 mg gestodene in an open-label study of healthy, female volunteers (aged 18–35 years). A total of 199 volunteers from two centers were requested to use the contraceptive patch (one patch/week for 3 weeks, followed by 1 week of no treatment), throughout two menstrual cycles. Ovarian activity was monitored by transvaginal ultrasonography and serum hormone determinations, and classified according to the Hoogland score. Ovulation inhibition was achieved in all participants (Hoogland score <6). Secondary efficacy measures, including suppression of serum concentrations of estradiol and progesterone, and of the mid-cycle luteinizing hormone surge, confirmed ovulation inhibition. Ovulation returned in 85.7% of participants during the first cycle after cessation of treatment. There were no abnormal changes in safety parameters. A large majority of users rated the contraceptive patch as ‘very convenient’. This study showed that the new, combined ethinylestradiol/gestodene contraceptive patch was highly effective in reversibly inhibiting ovulation, well tolerated and regarded as ‘very convenient’ by the majority of users. This new, transparent, transdermal matrix patch is an attractive alternative form of contraception. (author’s) Language: English Keywords: NETHERLANDS | RESEARCH REPORT | WOMEN | VOLUNTEERS AND VOLUNTARISM | ETHINYL ESTRADIOL | GESTODENE | CONTRACEPTIVE EFFECTIVENESS | OVULATION SUPPRESSION | CONTRACEPTIVE SAFETY | CONTRACEPTIVE METHOD ACCEPTABILITY | ULTRASONICS | USER COMPLIANCE | Europe, Western | Europe | Developed Countries | Demographic Factors | Population | Organization and Administration | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Mode of Action | Safety | Public Health | Health | Contraceptive Usage | Behavior Document Number: 278606 |
| 15. Peer Reviewed Title: Flutamide-metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third- to fourth-generation OC reduces body adiposity. Author: Ibáñez L; de Zegher F Source: Human Reproduction. 2004;19(8):1725-1727. Abstract: Low-dose flutamide–metformin has been developed as a background therapy for non-obese adolescents and young women with hyperinsulinaemic hyperandrogenism, a variant of polycystic ovary syndrome (PCOS). We verified whether the lipolytic efficacy of flutamide–metformin in women with PCOS is enhanced by giving an oral contraceptive (OC) co-therapy that contains drospirenone, instead of gestodene, as progestin. An open-labelled study was carried out in which non-obese women with PCOS (n = 29; age -20 years), who had been on a combination of flutamide (62.5 mg/day), metformin (850 mg/day) and ethinylestradiol–gestodene for 8–15 months, were randomized for replacement of the gestodene OC by a drospirenone OC. Assessments of endocrine–metabolic state and body composition (by dual-energy X-ray absorptiometry) were performed at randomization and after 6 months. The switch to drospirenone OC was accompanied by a reduction of total and abdominal fat (mean -0.8 and -0.5 kg) and by an increment of lean body mass (10.6 kg; all P < 0.01), so that body adiposity was strikingly reduced without changing body weight. In nonobese women with PCOS, low-dose flutamide–metformin reduces total and abdominal fat excess more effectively if contraceptive co-therapy contains drospirenone, instead of gestodene, as progestin. (author's) Language: English Keywords: SPAIN | RESEARCH REPORT | CLINICAL RESEARCH | YOUTH | ADOLESCENTS, FEMALE | ANDROGENS | OVARIAN CYSTS | GESTODENE | ORAL CONTRACEPTIVES, LOW-DOSE | HORMONE REPLACEMENT THERAPY | METABOLIC EFFECTS | BODY WEIGHT | HEALTH STATUS INDEXES | Developed Countries | Europe, Southwestern | Europe | Research Methodology | Age Factors | Population Characteristics | Demographic Factors | Population | Adolescents | Hormones | Endocrine System | Physiology | Biology | Diseases | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Oral Contraceptives | Contraceptive Methods | Treatment | Health Document Number: 273619 |
16.  Title: Effectiveness and acceptability of progestogens in combined oral contraceptives -- a systematic review. Author: Kulier R; Helmerhorst FM; Maitra N; Gülmezoglu M Source: Reproductive Health. 2004 Jun;1(1):[9] p.. Abstract: The progestogen component of oral contraceptives (OCs) has undergone changes since it was recognized that their chemical structure can influence the spectrum of minor adverse and beneficial effects. The objective of this review was to evaluate currently available low-dose OCs containing ethinylestradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates. The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases were searched. Randomized trials reporting clinical outcomes were considered for inclusion and were assessed for methodological quality and validity. Twenty–two trials were included in the review. Eighteen were sponsored by pharmaceutical companies and in only 5 there was an attempt for blinding. Most comparisons between different interventions included one to three trials, involving usually less than 500 women. Discontinuation was less with second-generation progestogens compared to first–generation (RR 0.79; 95% CI 0.69–0.91). Cycle control appeared to be better with second-compared to first generation progestogens for both, mono-and triphasic preparations (RR 0.69; 95% CI 0.52–0.91) and (RR 0.61; 95% CI 0.43–0.85), respectively. Intermenstrual bleeding was less with third compared to second-generation pills (RR 0.71; 95% CI 0.55–0.91). Contraceptive effectiveness of gestodene (GSD) was comparable to that of levonorgestrel (LNG), and had similar pattern of spotting, breakthrough bleeding and absence of withdrawal bleeding). Drospirenone (DRSP) was similar compared to desogestrel (DSG) regarding contraceptive effectiveness, cycle control and side effects. The third- and second-generation progestogens are preferred over first generation in all indices of acceptability. Current evidence suggests that GSD is comparable to LNG in terms of contraceptive effectiveness and for most cycle control indices. GSD is also comparable to DSG. DRSP is comparable to DSG. Future research should focus on independently conducted well designed randomized trials comparing particularly the third-with second-generation progestogens. (author's) Language: English Keywords: LITERATURE REVIEW | CLINICAL TRIALS | EVALUATION | WOMEN | ORAL CONTRACEPTIVES, COMBINED | CONTRACEPTIVE AGENTS, PROGESTIN | MENSTRUAL REGULATION | METRORRHAGIA | GESTODENE | CONTRACEPTIVE EFFECTIVENESS | LEVONORGESTREL | CONTRACEPTIVE SAFETY | CONTRACEPTION TERMINATION | Clinical Research | Research Methodology | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Female | Contraceptive Agents | Fertility Control, Postcoital | Bleeding | Signs and Symptoms | Diseases | Safety | Public Health | Health Document Number: 194580 |
| 17. Title: [The effectiveness and acceptability of oral contraceptives (Logest), containing 20 micrograms ethinylestradiol and 75 micrograms gestodene] Badanie skutecznosci i akceptacji stosowania pigulek antykoncepcyjnych Logest, zawierajacych 20 g etynyloestradiolu i 75 g gestodenu. Author: Lech MM; Swiatek EJ Source: Ginekologia Polska. 2004 Mar;75(3):209-214. Abstract: Significant factor that affects acceptance of a hormonal contraceptive agent is the frequency of bleeding and spotting (9). These symptoms may be related to the quantity, type and mutual proportions among the components of pills (6, 13). Although it is believed that while using preparations containing gestoden there is a lesser risk of irregular bleeding and spotting than with other progestagens (2), a low content of estrogens could contribute to the occurrence of intermenstrual bleeding/spotting. During the performance of the study a temporary (during the first three cycles of taking Logest) increase in the number of intermenstrual episodes of bleeding/spotting whose frequency became lesser with subsequent cycles of taking Logest were observed. In the same subjects, after six cycles of using Logest, intermenstrual bleeding/spotting were rarer than before taking this preparation. Another significant question decisive for the continuation of taking specific pills is their contribution to the increase of the body mass. Although some authors believe that women using hormonal treatment tend to get the increase their body mass (10), most of studies do not confirm such a relationship (7,8). The results of this (4) and other studies (3) justify the conclusion that using Logest does not contribute to the increase in the body mass. (excerpt) Language: Polish Keywords: RESEARCH REPORT | WOMEN | CONTRACEPTIVE USAGE | ORAL CONTRACEPTIVES | GESTODENE | BLEEDING | SIDE EFFECTS | BODY WEIGHT | PROGRAM ACCEPTABILITY | Demographic Factors | Population | Contraception | Family Planning | Contraceptive Methods | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Signs and Symptoms | Diseases | Treatment | Physiology | Biology | Program Evaluation | Programs | Organization and Administration Document Number: 277623 |
| 18. Peer Reviewed Title: Effect of a low-dose ethinylestradiol and gestodene in combination on the frequency of micronuclei in human peripheral blood lymphocytes of healthy women in vivo. Author: Loncar D; Milosevic-Djordjevié O; Zivanovic A; Grujicic D; Arsenijevic S Source: Contraception. 2004 Apr;69(4):327-331. Abstract: Background: Since most oral hormonal contraceptives contain a fixed combination of ethinylestradiol and gestodene as an estrogenic/progestogenic component, we decided to evaluate the possible mutagenic effect of a low-dose contraceptive pills containing 20 µg ethinylestradiol and 75 µg gestodene. Methods: A total of 30 healthy women received hormonal contraception during six consecutive menstrual cycles. A single daily dose was 20 µg ethinylestradiol and 75 µg gestodene. The pills were taken orally in a monthly cycle of 3 weeks on and 1 week off. In the investigation of the mutagenic effect of these contraceptive pills in vivo, the cytokinesis block micronucleus (CBMN) test was used, and the frequency of micronuclei (MN) in peripheral blood lymphocytes was determined. Results: Average MN frequency in women before therapy was 7.40 ± 0.75 MN/1000 analyzed cells, and after therapy was 7.37 ± 0.59 MN/1000 analyzed cells (p > 0.05). Conclusion: Our data suggest that oral contraception with 20 µg ethinylestradiol and 75 µg gestodene in combination during six consecutive menstrual cycles does not induce micronuclei in peripheral blood lymphocytes of women.(author's) Language: English Keywords: RESEARCH REPORT | WOMEN | CLIENTS | ORAL CONTRACEPTIVES | GESTODENE | ETHINYL ESTRADIOL | BLOOD | MENSTRUATION | Demographic Factors | Population | Program Activities | Programs | Organization and Administration | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Hemic System | Physiology | Biology | Reproduction Document Number: 191321 |
| 19. Peer Reviewed Title: Serum resistin levels in women taking combined oral contraceptives containing desogestrel or gestodene. Author: Rechberger T; Tomaszewski J; Pieprzowska-Bialek A; Kulik-Rechberger B; Skorupski P Source: Contraception. 2004 Jun;69(6):477-480. Abstract: Resistin is a hormone secreted by adipose tissue that could be involved in the development of insulin resistance. Previous studies confirmed that endogenous sex steroids may influence serum resistin concentration in women. The aim of our study was to investigate the influence of combined oral contraceptives containing desogestrel or gestodene on circulating levels of resistin. Fifty-three women were enrolled in the study. Thirteen patients received 20 µg ethinylestradiol/150 µg desogestrel, 15 women were treated with 20 µg ethinylestradiol/75 µg gestodene, 11 with 30 µg ethinylestradiol/150 µg desogestrel and 14 with 30 µg ethinylestradiol/75 µg gestodene. Blood samples for estimation of serum resistin and insulin levels were drawn before administration of oral contraceptive and after 6 cycles of therapy. We found that serum resistin level remained unchanged in women receiving ethinylestradiol/desogestrel and was reduced in women treated with formulations containing gestodene. We conclude that ethinylestradiol combined with desogestrel or gestodene is unlikely to induce insulin resistance through resistin pathway. (author's) Language: English Keywords: POLAND | RESEARCH REPORT | CLINICAL RESEARCH | COMPARATIVE STUDIES | WOMEN | ORAL CONTRACEPTIVES, COMBINED | DESOGESTREL | GESTODENE | GLUCOSE METABOLISM EFFECTS | ETHINYL ESTRADIOL | Europe, Central | Europe | Developing Countries | Research Methodology | Studies | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Carbohydrate Metabolic Effects | Metabolic Effects | Physiology | Biology | Contraceptive Agents, Estrogen Document Number: 192719 |
| 20. Peer Reviewed Title: A 13-month multicenter clinical experience of a low-dose monophasic oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene in Latin American women. [Experiencia clínica multicéntrica de 13-meses de un anticonceptivo oral monofásico de dosis baja con contenido de 20 microgramos de etinilestradiol y 75 microgramos de gestodeno en mujeres latinoamericanas] Author: Bassol S; Alvarado G; Gaona Arreola R; Celis-Gonzalez C; Perez Pena E Source: Contraception. 2003 May;67(5):367-372. Abstract: This prospective, multicenter study was conducted to evaluate the contraceptive reliability, cycle control and tolerability of a 21-day oral contraceptive regimen containing 20 µg ethinylestradiol and 75 µg gestodene in four Latin American countries (Mexico, Argentina, Brazil and Colombia). Participants took trial medication daily for 21 days. Contraceptive efficacy, cycle control and tolerability were evaluated over a period of 13 cycles. Efficacy data gathered from 5,109 treatment cycles were obtained from 393 participants. The trial medication proved to be an effective contraceptive and provided good cycle control. One pregnancy because of poor compliance was recorded. This resulted in a study Pearl index of 0.25. Forty-six percent of Latin American women reported one intracyclic spotting bleeding episode and 37.6% reported one intracyclic breakthrough bleeding (medium/excessive bleeding) episode during cycles 2–4 (primary target). Overall, intracyclic bleeding was reported in 41%. Overall, there was a trend towards a lower incidence of spotting in all the countries and this difference had statistical significance between Argentina and the others three countries (p < 0.05) during cycles 2–4. This trend was also apparent with respect to breakthrough bleeding, but again the difference did not achieve statistical significance. The discontinuation rate because of adverse events was low (3%); no serious adverse events were reported. More than 78% of the women in the four countries maintained constant body weight or lost weight (2 kg) during the study. The treatment effect on blood pressure was negligible. There were no appreciable changes in mean laboratory values over the course of the study. (author's) Spanish Abstract: Se realizó un estudio prospectivo, multicéntrico para evaluar la confiabilidad anticonceptiva, el control del ciclo y el grado de tolerancia de un protocolo de 21 días de anticonceptivos orales con un contenido de 20 µg de etinilestradiol y 75 µg de gestoden en cuatro países de América Latina (México, Argentina, Brasil y Colombia). Las participantes tomaron la medicación en estudio durante 21 días. Se evaluaron la eficacia anticonceptiva, el control del ciclo y el grado de tolerancia durante un período de 13 ciclos. Se reunieron datos de 5109 ciclos de tratamiento obtenidos de 393 participantes. La medicación en estudio resultó eficaz como anticonceptivo y en el control de los ciclos. Se registró un embarazo debido a falta de cumplimiento por parte de la paciente. Esto resultó en un índice Pearl de 0,25. El 46% de las mujeres latinoamericanas informó un episodio de oligometrorragia intramenstrual y el 37,6% informó un episodio de metrorragia intercurrente (hemorragia medio/excesivo) durante los ciclos 2 a 4 (objetivo primario). En total, el 41% informó metrorragia. En general, se manifestó una tendencia hacia la reducción de la incidencia de oligometrorragia en todos los países y esta diferencia resultó estadísticamente significativa entre Argentina y los otros tres países (p < 0,05) durante los ciclos 2 a 4. Esta tendencia también fue evidente con respecto a la hemorragia intercurrente, pero la diferencia no alcanzó relevancia estadística. La tasa de interrupción del tratamiento debido a eventos adversos fue baja (3%)y no se informaron episodios adversos graves. Más del 78% de las mujeres de los cuatro países mantuvieron su peso corporal constante o perdieron peso (2 kg) durante el estudio. El efecto del tratamiento sobre la presión arterial fue insignificante. No se observaron cambios apreciables en los valores medios de laboratorio durante la evolución del estudio. (del autor) Language: English Keywords: MEXICO | ARGENTINA | BRAZIL | COLOMBIA | LATIN AMERICA | EVALUATION REPORT | PROSPECTIVE STUDIES | RELIABILITY | CLINICAL RESEARCH | ADULTS | WOMEN | HUMAN VOLUNTEERS | STATISTICAL STUDIES | ORAL CONTRACEPTIVES | ETHINYL ESTRADIOL | GESTODENE | CONTRACEPTIVE USE-EFFECTIVENESS | CLINICAL TRIALS | North America | Americas | Developing Countries | South America, Southern | South America | South America, Eastern | South America, Northern | Evaluation | Studies | Research Methodology | Measurement | Age Factors | Population Characteristics | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Contraceptive Effectiveness Document Number: 178745 |
| 21. Title: How low can you get? Author: Brincat M; Baron YM; Galea R Source: Annals of the New York Academy of Sciences. 2003 Nov;997:158-162. Abstract: Since the early 1960s the side effects of oral contraceptives have been known to be related to the high doses (50 µg) of ethinyl estradiol used. Research has focused on reducing the dose of both the estrogen and progestin components to reduce these side effects. While reducing the dose of both components, the contraceptive efficacy has to be maintained so as to retain a satisfactory Pearl index. These requirements appear to have been attained with 24-day regimen of a low-dose pill (15 µg of ethinyl estradiol and 60 µg of gestedone) as one part of an open-label noncomparative multicenter study. This paper reports our unit's results, which indicate that the low-dose pill promises to reduce contraceptive-related side effects, to encourage better compliance, and as corollary, to retain a satisfactory Pearl index (author's) Language: English Keywords: MALTA | RESEARCH REPORT | COMPARATIVE STUDIES | ADMINISTRATION AND DOSAGE | ORAL CONTRACEPTIVES, LOW-DOSE | CONTRACEPTIVE AGENTS, SIDE EFFECTS | PEARL'S FORMULA | CONTRACEPTIVE AGENTS, PROGESTIN | ETHINYL ESTRADIOL | GESTODENE | DESOGESTREL | MENSTRUATION DISORDERS | Developed Countries | Europe, Southern | Europe | Studies | Research Methodology | Drugs | Treatment | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents | Contraceptive Use-Effectiveness | Contraceptive Effectiveness | Contraceptive Agents, Female | Contraceptive Agents, Estrogen | Diseases Document Number: 277748 |
| 22. Peer Reviewed Title: Influence of the third generation pill controversy on prescriptions for oral contraceptives among first time users: population based study. Author: de Jong-van den Berg L; Tobi H; Bijker B; van den Berg P Source: BMJ. British Medical Journal. 2003 Feb 1;326(7383):254. Abstract: The number of women prescribed the third generation pill decreased dramatically after the pill scare in 1995; the decrease was most notable for women under 25. The percentage of women prescribed a third generation oral contraceptive continued to decline over the following six years. (excerpt) Language: English Keywords: NETHERLANDS | RESEARCH REPORT | STUDIES | ORAL CONTRACEPTIVES | DESOGESTREL | GESTODENE | PRESCRIPTIONS | CONTRACEPTIVE SAFETY | SIDE EFFECTS | Europe, Western | Europe | Developed Countries | Research Methodology | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Distributional Activities | Program Activities | Programs | Organization and Administration | Safety | Public Health | Health | Treatment Document Number: 175212 |
| 23. Peer Reviewed Title: [Effect and control of oral contraceptive Minesse (15 mkg EE / 60 mkg Gestoden) on menstrual cycle and body weight] Author: Krusteva Source: Akusherstvo i Ginekologiia. 2003;42(5):46-48. Abstract: The first hormonal contraception pills contained high levels of steroid hormones in order to definitely prevent ovulation. Very soon afterwards it became obvious that ovulation can be prevented also with significantly lower levels. From that moment on begins the trend of continuing reduction of the steroid levels aiming at limiting any potential risks. The level of ethinyl estradiol (EE) was reduced to 20 µg at the end of the eighties. The first serious studies of still lower levels - 15 µg - were presented at the Fifth Congress of the European Contraception Association in Prague in 1998. Shortly afterwards, 15-µg products became established on the pharmaceutical market. In the interpretation of their effects one fact is often overlooked: that along with the reduction of the estrogen level there is also a reduction of the progestin level, namely, that there is a search for a balance between the two components on a new level. Taking into account that the pill schedule has changed - from the classical 21 + 7 to the 24 + 4 - various logical questions arise. Is it possible to effectively prevent ovulation with the lower steroid levels; can the new schedule maintain the stability of the endometrium; is there a real reduction of the side effects; are the non-contraceptive benefits preserved etc. Some of these questions have already been answered, but it is worth pointing out that the experience with 15-µg EE products worldwide is limited and that they will be the focus of serious scientific interest in the coming years. The goal of the current study is to establish the effectiveness of the combination of 15 µg EE/ 60 µg Gestoden and its effect on the menstruation cycle and the body mass index. (excerpt) Language: Bulgarian Keywords: EUROPE | CONFERENCES AND CONGRESSES | ORAL CONTRACEPTIVES | SIDE EFFECTS | MENSTRUAL CYCLE | BLEEDING | BODY WEIGHT | GESTODENE | Developed Countries | Contraceptive Methods | Contraception | Family Planning | Treatment | Menstruation | Reproduction | Signs and Symptoms | Diseases | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 277775 |
| 24. Peer Reviewed Title: Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Author: Nappi C; Di Spiezio Sardo A; Acunzo G; Bifulco G; Tommaselli GA Source: Contraception. 2003 May;67(5):355-359. Abstract: In this prospective, controlled, randomized study, we compared the effect of a low-dose 21-day combined oral contraceptive (COC) containing 20 µg ethinyl estradiol (EE) and 75 µg gestodene (GTD) (Group A; n = 19) with an ultra-low-dose 24-day COC containing 15 µg EE and 60 µg GTD (Group B; n = 18) on bone turnover and bone mineral density (BMD) in young, fertile women. Nineteen healthy fertile women were used as untreated controls (Group C). At 3, 6, 9 and 12 months of the study serum osteocalcin (BGP), urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) were measured in all subjects. At baseline and after 12 months BMD was determined at lumbar spine by dual-energy X-ray absorptiometry in all patients. In both Groups A and B, urinary levels of PYD and D-PYD at 6, 9 and 12 months, were significantly reduced in comparison with basal values and with control subjects (p < 0.05). No significant differences in urinary PYD and D-PYD levels were observed between Groups A and B during the entire period of treatment. At 12 months, no statistically significant difference in spinal BMD values was detected between the three groups and in comparison with basal values. The present study suggests that the two COCs could exert a similar positive effect on bone turnover in young postadolescent women, without any significant and appreciable modification of BMD. (author's) Language: English Keywords: ITALY | RESEARCH REPORT | PROSPECTIVE STUDIES | CONTROL GROUPS | CLINICAL RESEARCH | STATISTICAL STUDIES | YOUTH | WOMEN | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, LOW-DOSE | ETHINYL ESTRADIOL | GESTODENE | SKELETAL EFFECTS | Europe, Southern | Europe | Developed Countries | Studies | Research Methodology | Age Factors | Population Characteristics | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Physiology | Biology Document Number: 178743 |
| 25. Peer Reviewed Title: Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism. Author: Ludicke F; Gaspard UJ; Demeyer F; Scheen A; Lefebvre P Source: Contraception. 2002 Dec;66(6):411-415. Abstract: This study compared the impact on carbohydrate metabolism of two combinedoral contraceptives (COCs). This open-label, single-center trial enrolled participants for a total of 15 cycles. Thirty-six women were randomized to receive either 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) or 20 microg ethinyl estradiol and 150 microg desogestrel (DSG) daily for 21 days out of 28. A glucose tolerance test was performed at baseline and cycles 6 and 13. The area under the curve (AUC) for glucose increased in both study groups. The change was statistically significant (p=0.036) for the 20 EE/75 GSD group at cycle 6 versus baseline. Fasting blood glucose at cycle 13 was significantly (p<0.01) higher for both treatment groups compared to baseline. No changes were found for fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C-peptide. Both regimens were well tolerated. Gestodene and desogestrel in combination with 20-microg ethinyl estradiol induce similar changes in carbohydrate metabolism which are smaller than those described earlier for COCs containing higher estrogen doses or more androgenic progestins such as levonorgestrel. (author’s) Language: English Keywords: RESEARCH REPORT | COMPARATIVE STUDIES | RANDOMIZED RESPONSE TECHNIC | ADULTS | WOMEN | ORAL CONTRACEPTIVES, LOW-DOSE | GESTODENE | DESOGESTREL | CARBOHYDRATES | GLUCOSE TOLERANCE TEST | CLINICAL TRIALS | Studies | Research Methodology | Questionnaire Design | Survey Methodology | Surveys | Sampling Studies | Age Factors | Population Characteristics | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Physiology | Biology | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Clinical Research Document Number: 173858 |
| 26. Peer Reviewed Title: Long-term effects of combined oral contraceptives on markers of endothelial function and lipids in healthy premenopausal women. Author: Merki-Feld GS; Rosselli M; Dubey RK; Jager AW; Keller PJ Source: Contraception. 2002;65:231-6. Abstract: The aim of this prospective cross-over study was to investigate the effect of two low-dosed oral contraceptives (OCs) on markers of endothelial function and plasma lipids. 12 healthy, non-smoking women (mean age: 21.7 years) were recruited from the family planning clinic of the university hospital Zurich. For 6 months the participants received a treatment with two contraceptive pills containing 30 mcg ethinyl estradiol/150 mcg levonorgestrel (three cycles) and 30 mcg ethinyl estradiol/75 mcg gestodene (three cycles). Plasma levels of endothelin-1, nitric oxide, cholesterol, and high density lipoprotein were measurement before and during treatment with both OC treatments. No significant changes in the plasma levels of nitric oxide and endothelin-1, both important regulators of the vascular tone, were observed during oral contraceptive use. A significant negative correlation was found between nitric oxide and endothelin-1 and nitric oxide and cholesterol. There was a positive correlation between endothelin-1. In conclusion, the investigated contraceptive pills did not cause major changes in circulating nitric oxide and endothelin-1 plasma levels. (author's) Language: English Keywords: SWITZERLAND | RESEARCH REPORT | PROSPECTIVE STUDIES | CLINICAL RESEARCH | ORAL CONTRACEPTIVES, COMBINED | ETHINYL ESTRADIOL | LEVONORGESTREL | GESTODENE | LONGTERM EFFECTS | CARDIOVASCULAR EFFECTS | RISK FACTORS | Developed Countries | Europe, Central | Europe | Studies | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Time Factors | Population Dynamics | Demographic Factors | Population | Physiology | Biology Document Number: 166208 |
| 27. Peer Reviewed Title: Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills? A discussion based on recent recommendations from the European agency for evaluation of medicinal products regarding third generation oral contraceptive pills. Author: Odlind V; Milsom I; Persson I; Victor A Source: Acta Obstetrica et Gynecologica Scandinavica. 2002 Jun;81(6):482-490. Abstract: Recent studies have indicated that the risk of thromboembolic disease (VTE) in users of combined oral contraceptive pills (COCs) varies not only with estrogen dose, but also with the progestogen in pills with the same estrogen dose. The aim of this article is to discuss sex hormone binding globulin (SHBG) as a marker of estrogenicity and as a surrogate indicator for the potential risk of VTE in users of COC. Using data from the literature, we investigated the relationship between the risk of VTE with various COCs and their effects on SHBG. We also collected data on the effects on SHBG by some combined preparations, where there are no VTE data. There appears to be a relationship between the risk of VTE and the effect on SHBG. Monophasic preparations containing levonorgestrel, having the lowest risk of VTE, cause an average SHBG increase of around 50%. COCs containing desogestrel or gestodene cause an average SHBG increase of 200–300%. A preparation with cyproterone acetate, carrying a higher risk of VTE than desogestrel and gestodene, cause a 300–400% SHBG increase. With the recently developed combined preparations, there is a 150% SHBG increase with norgestimate and a 250–300% increase with drosperinone and dienogest. We propose that the change in SHBG with a COC could be interpreted as a measure of total estrogenicity and used as a predictor of the risk of VTE. Preparations containing drosperinone, dienogest, cyproterone acetate and norgestimate are equally or more estrogenic than the more thoroughly studied COCs, containing desogestrel or gestodene and should not be considered a safer substitute. (author's) Language: English Keywords: EUROPE | RESEARCH REPORT | WOMEN | ORAL CONTRACEPTIVES | THROMBOEMBOLISM | DESOGESTREL | GESTODENE | RISK FACTORS | Developed Countries | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Embolism | Vascular Diseases | Diseases | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Biology Document Number: 192733 |
| 28. Title: Sweet's syndrome induced by oral contraceptive. Author: Saez M; Garcia-Bustinduy M; Noda A; Guimera F; Dorta S; Escoda M; Fagundo E; Sanchez R; Martin-Herrera A; Garcia Montelongo R Source: Dermatology. 2002;204(1):84. Abstract: All criteria for drug-induced Sweet’s syndrome are fulfilled by our patient. Only a single case in which Sweet’s syndrome was believed to be precipitated by oral contraceptives could be found. Nevertheless as more cases of drug-induced Sweet’s syndrome are being reported in the literature, we suggest that a drug aetiology should be sought in cases of Sweet’s syndrome and we recommend that a careful drug history should be included in the assessment of all the cases of this syndrome. (excerpt) Language: English Keywords: SPAIN | SUMMARY REPORT | ADULTS | WOMEN | ORAL CONTRACEPTIVES, SIDE EFFECTS | GESTODENE | ETHINYL ESTRADIOL | LABORATORY EXAMINATIONS AND DIAGNOSES | SIDE EFFECTS | CONTRACEPTIVE METHODS | Developed Countries | Europe, Southwestern | Europe | Age Factors | Population Characteristics | Demographic Factors | Population | Contraceptive Safety | Safety | Public Health | Health | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Examinations and Diagnoses | Treatment Document Number: 176186 |
| 29. Peer Reviewed Title: A comparison of cycle control, efficacy, and side effects among healthy Thai women between two low-dose oral contraceptives containing 20 micrograms ethinylestradiol / 75 micrograms gestodene (Meliane) and 30 micrograms ethinylestradiol / 75 micrograms gestodene (Gynera). Author: Taneepanichskul S; Kriengsinyot R; Jaisamrarn U Source: Contraception. 2002 Dec;66(6):407-409. Abstract: The purpose of this study was to compare cycle control, efficacy and side effects of an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene, with a reference preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. From the study, it was demonstrated that the two regimens had no difference in cycle control, efficacy, and side effects. The occurrence of spotting and breakthrough bleeding was low and was not different between these two preparations. The most common adverse events in both treatment groups were nausea, vomiting, dizziness, and chloasma. There were no statistically significant change in body weight and blood pressure in both groups at the end of study. It is concluded that both preparations are good cycle control, reliable and low side effects oral contraceptives. (author’s) Language: English Keywords: THAILAND | EVALUATION REPORT | COMPARATIVE STUDIES | ADULTS | WOMEN | ORAL CONTRACEPTIVES, LOW-DOSE | ETHINYL ESTRADIOL | GESTODENE | CONTRACEPTIVE EFFECTIVENESS | SIDE EFFECTS | Developing Countries | Asia, Southeastern | Asia | Evaluation | Studies | Research Methodology | Age Factors | Population Characteristics | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Treatment Document Number: 173857 |
| 30. Title: Progestins and thrombosis. Author: Burkman RT; Heinemann LA Source: Dialogues in Contraception. 2001 Winter;7(3):5-7, 8. Abstract: The absolute risk of venous thrombosis and embolism (VTE)--a rare, usually mild event--is small. In the general population of reproductive-age women, the published annual incidence of VTE ranges around one event per 10,000 women. In women taking any combination oral contraceptives (OC), this incidence is increased to 3-4/10,000 women annually. According to the most recent official statement of the European Drug Authority, it is probable that women taking OCs containing desogestrel or gestodene have a small excess risk (best estimate 1.5- 2.0 increased risk) compared with OCs containing other progestins and the same dose of ethinyl estradiol, although the published risk estimates range from 0.8- 4.2. Pregnancy increases the estimated incidence to 6/10,000. With the existence of a familial thrombophilia, such as factor V Leiden mutation, the risk of thrombosis is about 8/10,000 in OC nonusers, and nearly 30/10,000 in OC users. The benefits of OC use in healthy women far outweigh the risks. The benefits and risks of OC use should not be considered in isolation. Medical counseling of women should take into account all aspects of benefit and risk (including pre-existing risk factors), and evaluate these aspects in the context of the individual woman. (author's) Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | STUDIES | ORAL CONTRACEPTIVES | CONTRACEPTIVE AGENTS, PROGESTIN | DESOGESTREL | GESTODENE | THROMBOSIS | RISK FACTORS | Developed Countries | North America | Americas | Research Methodology | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Female | Contraceptive Agents | Thromboembolism | Embolism | Vascular Diseases | Diseases | Biology Document Number: 165315 |
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