1.  Peer Reviewed Title: Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate. Author: Rible RD; Taylor D; Wilson ML; Stanczyk FZ; Mishell DR Jr Source: Contraception. 2009 Mar;79(3):182-8. Abstract: BACKGROUND: Combined oral contraceptive (COC) formulations with 20 mcg ethinyl estradiol (EE) have a greater incidence of ovarian hormone production and follicular development, which can be managed by shortening the number of hormone-free days per COC cycle. This study evaluates differences in follicular development during a 7-day versus 4-day hormone-free interval in a COC regimen with 20 mcg EE and 1 mg norethindrone acetate. STUDY DESIGN: Forty-one healthy women were randomized in an open-label fashion to this formulation in either a 24/4 or a 21/7 day regimen for three cycles. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and inhibin B were measured daily from Cycle 2, Day 21 to Cycle 3, Day 3 and on Day 7 of Cycle 3. Follicular diameter and Hoogland score were calculated on Cycle 2, Days 21, 24 and 28 and Cycle 3, Days 3 and 7. RESULTS: Sixty-six percent of subjects in the 21/7 group and 70% of the subjects in the 24/4 group developed a follicle greater than 10 mmdiameter. Ovarian steroid hormone levels, Hoogland scores and bleeding patterns were not statistically significant between the groups. CONCLUSION: In contrast to prior studies, this analysis suggests no difference in follicle development or bleeding patterns among women receiving a 21/7 or 24/4 regimen of a 20-mcg EE/1-mg norethindrone acetate COC. Language: English Keywords: CALIFORNIA | RESEARCH REPORT | CLINICAL RESEARCH | CASE CONTROL STUDIES | COMPARATIVE STUDIES | WOMEN | FOLLICLE STIMULATING HORMONE | ORAL CONTRACEPTIVES, COMBINED | ETHINYL ESTRADIOL | NORETHINDRONE | ADMINISTRATION AND DOSAGE | MENSTRUATION | TIME FACTORS | United States of America | North America | Americas | Developed Countries | Research Methodology | Studies | Demographic Factors | Population | Gonadotropins, Pituitary | Gonadotropins | Hormones | Endocrine System | Physiology | Biology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Reproduction | Population Dynamics Document Number: 330059 |
| 2. Peer Reviewed Title: Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone. Author: Scholler-Gyure M; Kakuda TN; Woodfall B; Aharchi F; Peeters M; Vandermeulen K; Hoetelmans RM Source: Contraception. 2009 Jul;80(1):44-52. Abstract: BACKGROUND: Etravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) active against NNRTI-resistant HIV, is an inducer of CYP3A4 and an inhibitor of CYP2C9/19. STUDY DESIGN: The effect of etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone was assessed in 30 HIV-negative females. Following a run-in cycle with ethinylestradiol/norethindrone, the pharmacokinetics of ethinylestradiol and norethindrone was assessed on Day 15 of Cycle 2. Etravirine 200 mg bid was coadministered on Day 1 to Day 15 of Cycle 3, with pharmacokinetic assessments of ethinylestradiol, norethindrone and etravirine on Day 15. RESULTS: When combined with etravirine, the least-squares means (LSM) ratios (90% confidence interval) for ethinylestradiol AUC(24h), C(max) and C(min) were 1.22 (1.13-1.31), 1.33 (1.21-1.46) and 1.09 (1.01-1.18), respectively, compared to administration alone. LSM ratios for norethindrone parameters were 0.95 (0.90-0.99), 1.05 (0.98-1.12) and 0.78 (0.68-0.90), respectively. CONCLUSION: These changes are not considered clinically relevant. No loss in contraceptive efficacy is expected when coadministered with etravirine. Language: English Keywords: BELGIUM | UNITED STATES OF AMERICA | RESEARCH REPORT | CLINICAL TRIALS | HUMAN VOLUNTEERS | WOMEN | ANTIRETROVIRAL DRUGS | DRUG INTERACTIONS | ORAL CONTRACEPTIVES | ETHINYL ESTRADIOL | NORETHINDRONE | ENZYMATIC EFFECTS | SIDE EFFECTS | LABORATORY PROCEDURES | Europe, Western | Europe | Developed Countries | North America | Americas | Clinical Research | Research Methodology | Demographic Factors | Population | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Drugs | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Enzymes and Enzyme Inhibitors | Physiology | Biology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses Document Number: 342790 |
| 3. Title: The Effect of Etoricoxib on the Pharmacokinetics of Oral Contraceptives in Healthy Participants. Author: Schwartz J; Hunt T; Smith WB; Wong P; Larson P; Crumley T; Mehta A; Gottesdiener K; Agrawal N Source: Journal of Clinical Pharmacology. 2009 May 14; Abstract: The pharmacokinetics of oral contraceptive (OC) components, ethinyl estradiol (EE) and norethindrone (NET), were evaluated after coadministration with etoricoxib in 3 double-blind, randomized, 2-period crossover studies of healthy women. There were 16, 39, and 24 participants enrolled in studies 1 (part I, part II), and 2, respectively. Each participant received triphasic OC (EE 35 microg/NET 0.5 mg x 7 days, 0.75 mg x 7 days, 1.0 mg x 7 days) throughout each 28-day period. OC was coadministered with 21 days of etoricoxib daily followed by placebo for 7 days; the alternate period followed the reverse regimen (placebo to etoricoxib). Study 1 (part I) examined concurrent (morning) administration of OC/etoricoxib 120 mg, study 1 (part II) examined staggered (morning/night) administration of OC/etoricoxib 120 mg, and study 2 examined concurrent (morning) administration of OC/etoricoxib 60 mg. Coadministration of OC and etoricoxib 120 mg once daily was associated with a ~50% to 60% increase in EE concentrations, whereas etoricoxib 60 mg once daily was associated with a ~37% increase in EE concentrations. Coadministration of OC and etoricoxib was generally well tolerated. A clinically important change in NET AUC0-24 h was not observed. Adverse events included dyspepsia, diarrhea, headache, nausea, fatigue, loss of appetite, and taste disturbance. Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | CLINICAL TRIALS | DOUBLE-BLIND STUDIES | WOMEN | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, SIDE EFFECTS | ETHINYL ESTRADIOL | NORETHINDRONE | ADMINISTRATION AND DOSAGE | TIME FACTORS | DRUG INTERACTIONS | DIARRHEA | HEADACHE | NAUSEA | Developed Countries | North America | Americas | Clinical Research | Research Methodology | Studies | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Safety | Safety | Public Health | Health | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Population Dynamics | Diseases | Signs and Symptoms Document Number: 341140 |
| 4. Peer Reviewed Title: Monthly injectable contraceptive use by adolescents in Brazil: Evaluation of clinical aspects. Author: Guazzelli CA; Jacobucci MS; Barbieri M; Araujo FF; Moron AF Source: Contraception. 2007 Jul;76(1):45-48. Abstract: This prospective noncomparative observational study evaluated the clinical symptoms, body weight and blood pressure of 38 adolescents receiving a monthly injectable contraceptive containing estradiol valerate 5 mg and norethisterone 50 mg. The volunteers, aged 16-19 years, were examined monthly during 1 year and asked about the following symptoms at baseline: dysmenorrhea, headache, breast tenderness, leg pain and irritability. There was a constant and gradual decline in each of the above symptoms over time, and there was a statistically significant difference between symptoms reported at the first visit and subsequent appointments. Body weight and blood pressure did not change significantly during the 1-year period. No pregnancies were observed. These findings suggest that monthly injectable contraception with estradiol valerate 5 mg/norethisterone 50 mg represents a highly effective and well-tolerated contraceptive for teens. (author's) Language: English Keywords: BRAZIL | RESEARCH REPORT | PROSPECTIVE STUDIES | ADOLESCENTS, FEMALE | PREMENSTRUAL TENSION | EXAMINATIONS AND DIAGNOSES | INJECTABLES | ESTRADIOL | NORETHINDRONE | ADMINISTRATION AND DOSAGE | BODY WEIGHT | BLOOD PRESSURE | South America, Eastern | South America | Latin America | Americas | Developing Countries | Studies | Research Methodology | Adolescents | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | Menstruation Disorders | Diseases | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Methods | Contraception | Family Planning | Estrogens | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Drugs | Treatment | Hemic System Document Number: 317957 |
| 5. Peer Reviewed Title: Development of a high-performance liquid chromatographic method for the determination of mifepristone in human plasma using norethisterone as an internal standard: Application to pharmacokinetic study. Author: Guo Z; Wang S; Wei D; Zhai J Source: Contraception. 2007 Sep;7(3):228-323. Abstract: The objective of this study was to develop a simple, sensitive, stable and validated HPLC method for the determination of mifepristone levels in human plasma. Solid-phase extraction cartridges were used to extract plasma samples. Separation was carried out on a C/18 column maintained at 20°C with acetonitrile-water (80:20, v/v) as mobile phase at a flow rate of 0.6 mL/min. Norethisterone was employed as the internal standard. Dual wavelength mode was used, with mifepristone monitored at UV 302 nm and norethisterone at 240 nm. The calibration curve was linear in the concentration range of 5-10000 ng/mL, with linear correlation coefficient r being 0.9999. The limit of detection for the assay was 3 ng/mL. The inter-day accuracy ranged from 92.4% to 98.4% and precision 3.6% to 11.4%. The intra-day accuracy ranged from 92.1% to 100.6% and precision 4.7% to 12.2%. The absolute recovery was 91.7-100.1%. Plasma samples were stable for at least 1 month if stored at -20°C. This validated HPLC method was successfully applied to pharmacokinetic study of mifepristone in human plasma samples collected from volunteers after oral administration of 10 mg mifepristone. The simple, accurate and stable method allows the sensitive determination of mifepristone in human plasma at the nanogram level. It could be applied to assess the plasma level of mifepristone in women up to 5 days after oral administration of 10 mg mifepristone. (author's) Language: English Keywords: CHINA | RESEARCH REPORT | RESEARCH AND DEVELOPMENT | RU-486 | NORETHINDRONE | ADMINISTRATION AND DOSAGE | LABORATORY PROCEDURES | Asia, Eastern | Asia | Developing Countries | Technology | Economic Factors | Hormone Antagonists | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Laboratory Examinations and Diagnoses | Examinations and Diagnoses Document Number: 319363 |
| 6. Peer Reviewed Title: Injectable contraception. Author: Haider S; Darney PD Source: Clinical Obstetrics and Gynecology. 2007 Dec;50(4):898-906. Abstract: Injectable contraceptive methods are safe, highly efficacious, and commonly used worldwide. Depo-Provera (depot-medroxyprogesterone acetate) is the most commonly used injectable in the United States. It is a convenient, discrete, and low-maintenance method, and is ideal for patients with contraindications to estrogen use and certain medical conditions. In addition, there are many noncontraceptive benefits to Depo-Provera use. Side effects with this method including irregular bleeding, breast tenderness, weight gain, and the impact on bone mineral density should be taken into consideration when prescribing the method. Other injectables such as Mesigyna and norethindrone enanthate are widely used outside the United States. (author's) Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | CLINICAL RESEARCH | WOMEN | INJECTABLES | DEPO-PROVERA | CONTRACEPTIVE EFFECTIVENESS | CONTRACEPTIVE SAFETY | CONTRACEPTIVE AGENTS, SIDE EFFECTS | CONTRACEPTIVE AGENTS, ESTROGEN | NORETHINDRONE | Developed Countries | North America | Americas | Research Methodology | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Medroxyprogesterone Acetate | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Safety | Public Health | Health Document Number: 322249 |
| 7. Title: A semi-automated 96-well plate method for the simultaneous determination of oral contraceptives concentrations in human plasma using ultra performance liquid chromatography coupled with tandem mass spectrometry. Author: Licea-Perez H; Wang S; Bowen CL; Yang E Source: Journal of Chromatography B. 2007 Jun;852(1-2):69-76. Abstract: Two semi-automated, relatively high throughput methods using ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) were developed for the simultaneous determination of ethinyl estradiol (EE) in combination with either 19-norethindrone (NE) or levonorgestrel (LN) in human plasma. Using 300 µL plasma, the methods were validated over the concentration ranges of 0.01-2 ng/mL and 0.1-20 ng/mL for EE and NE (or LN), respectively. The existing methods for the determination of the oral contraceptives in human plasma require large volumes of plasma (>/= 500µL), and sample extraction is labor-intensive. The LC run time is at least 6 min, enabling analysis of only about 100 samples a day. In the present work the throughput was greatly improved by employing a semi-automated sample preparation process involving liquid-liquid extraction and derivatization with dansyl chloride followed by UPLC separation on a small particle size column achieving a run time of 2.7 min. The validation and actual sample analysis results show that both methods are rugged, precise, accurate, and well suitable to support pharmacokinetic studies where approximately 300 samples can be extracted and analyzed in a day. (author's) Language: English Keywords: UNITED STATES OF AMERICA | METHODOLOGICAL STUDIES | EVALUATION RESEARCH | CLINICAL RESEARCH | WOMEN | ORAL CONTRACEPTIVES, COMBINED | LABORATORY EXAMINATIONS AND DIAGNOSES | LABORATORY PROCEDURES | BLOOD | ANALYSIS | ETHINYL ESTRADIOL | TIME FACTORS | LEVONORGESTREL | NORETHINDRONE | PRODUCTIVITY | Developed Countries | North America | Americas | Evaluation Methodology | Evaluation | Research Methodology | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Hemic System | Physiology | Biology | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Population Dynamics | Contraceptive Agents, Progestin | Economic Development | Economic Factors Document Number: 320672 |
| 8. Peer Reviewed Title: Comparison of two forms of continuous combined hormone replacement therapy with respect to metabolic effects. Author: Tugrul S; Yildirim G; Pekin O; Uslu H; Kutlu T Source: Archives of Gynecology and Obstetrics. 2007 May;275(5):335-339. Abstract: The objective was to compare the metabolic effects of two frequently used continuous hormone replacement therapies. Two hundred and forty-six menopausal women, aged between 41 and 57 years were enrolled in the present study. They were randomized to receive either estrogen + 2.5 mg medroxyprogesterone acetate (CEE/MPA) or 1 mg 17 Language: English Keywords: TURKEY | RESEARCH REPORT | WOMEN | MENOPAUSE | METABOLIC EFFECTS | HORMONE REPLACEMENT THERAPY | AGE FACTORS | BODY WEIGHT | SIDE EFFECTS | MEDROXYPROGESTERONE ACETATE | NORETHINDRONE | CHOLESTEROL | Developing Countries | Europe, Southeastern | Europe | Demographic Factors | Population | Reproduction | Physiology | Biology | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Population Characteristics | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Lipids Document Number: 315235 |
| 9. Title: What one should know about the Drug 'N' Tablet. Author: Britwum PK Source: Ghana Pharmaceutical Journal. 2006;:67-68. Abstract: N-Tablet has become a popular name or short form of Norethisterone 5mg tablet, which usually comes as an oral tablet. Norethisterone is a synthetic sex hormone and belongs to the group of sex hormones referred to as progestogens. It also falls under the testosterone analogue class of progestogens. The article reviews the uses, contraindications, and side effects of the tablet. It also reports on a survey conducted to determine the demand for oral use of Norethisterone 5mg tablets in Kumasi Metropolis in 2004. Language: English Keywords: GHANA | NORETHINDRONE | CONTRAINDICATIONS | SIDE EFFECTS | RESEARCH REPORT | CLINICAL RESEARCH | CONTRACEPTION RESEARCH | Developing Countries | Africa, Western | Africa, Sub Saharan | Africa | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Research Methodology Document Number: 328119 |
| 10. Peer Reviewed Title: Preferences between injectable contraceptive methods among South African women. Author: Morroni C; Myer L; Moss M; Hoffman M Source: Contraception. 2006 Jun;73(6):598-601. Abstract: The objective was to examine South African women’s preferences between depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN), as well as the reasons for and correlates of these preferences. A cross-sectional study among women attending 26 primary health care clinics across the Western Cape Province. Of 893 women participating in the survey, 57% (n = 511) and 45% (n = 399) had ever used DMPA and NET-EN, respectively. Among women who knew of both injectables, 46% stated a preference for DMPA (n = 365) and 37% stated a preference for NET-EN (n = 297). Most women who preferred DMPA thought that it was more effective in preventing pregnancy, while women who preferred NETEN stated that it was preferable for women who wanted children in the future. Preferences for NET-EN were independently associated with younger age, higher education and living in an urban area. These findings suggest that there are significant misperceptions among women regarding the differences between DMPA and NET-EN, which may have important resource implications for contraceptive services. It is likely that these misperceptions arise from popular discourse and individual user experiences, as well as poor communication with and counseling of women on the part of providers. Interventions aimed at both users and providers are required to dispel the myths and misinformation regarding progestogen-only injectable methods. (author's) Language: English Keywords: SOUTH AFRICA | RESEARCH REPORT | CROSS SECTIONAL ANALYSIS | WOMEN | FAMILY PLANNING ACCEPTORS | INJECTABLES | MEDROXYPROGESTERONE ACETATE | NORETHINDRONE | CONTRACEPTIVE METHOD ACCEPTABILITY | CONTRACEPTIVE USAGE DETERMINANTS | INFORMED CHOICE | Developing Countries | Africa, Southern | Africa, Sub Saharan | Africa | Research Methodology | Demographic Factors | Population | Family Planning Programs | Family Planning | Contraceptive Methods | Contraception | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Usage Document Number: 300856 |
| 11. Title: Progestins and estrogens and Alzheimer's disease. Author: Honjo H; Iwasa K; Kawata M; Fushiki S; Hosoda T Source: Journal of Steroid Biochemistry and Molecular Biology. 2005 Feb;93(2-5):305-308. Abstract: Sex-specific incidence rates for Alzheimer's disease (AD) are higher in women than men. Many fundamental researches and some clinical investigations have reported therapeutic and preventive effects of estrogens on AD. ButWHIMS[S.A. Shumaker,C.Legault, S.R. Rapp, L. Thal, R.B. Wallace, J.K. Ockene, S.L. Hendrix, B.N. Jones IIIrd, A.R. Assaf, R.D. Jackson, J.M. Kotchen, S. Wabertheil-Smoller, J. Wactawsk- Wende, WHIMS investigators, Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The women's health initiative memory study: a randomized controlled trial, JAMA 289 (2003) 2651-2662], which used daily continuous hormone replacement therapy (HRT), reported that the hazard ratio of the HRT for probable dementia was 2.05. Effect of progestins, and continuous (not cyclically) HRT, even only with estrogen should be reconsidered. In our clinical study, conjugated equine estrogen (CEE) alone showed good changes of psychiatric tests for AD on the 3rd week, but addition of medroxyprogesterone acetate (MPA) or norethindrone since 4th week suppressed these tests. Using human umbilical vein epithelial cell (HUVEC), levonorgestrel (LNG), norethindrone acetate (NETA), MPA increased intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion melocule-1 (VCAM-1) and E-secretin but dienogest (DNG) showed no effect. In vitro flow system, estradiol (E2), suppressed adhesion of white cell, but LNG, NETA, MPA increased the adhesions. DNG showed less effect. Non-feminizing estrogen J 861, which has 8,9 double bond and straight in its structure and has less effect on sexual organs. J 861 has shown ameliorative effects on central nervous system (CNS) (increasing of cholineacetyltransferase immunoreactive cells in substantia innominata (SI), etc.) like E2. More investigations about progestins and estrogens and AD should be done. Language: English Keywords: JAPAN | RESEARCH REPORT | CLINICAL RESEARCH | WOMEN | CENTRAL NERVOUS SYSTEM EFFECTS | CHRONIC DISEASES | CONTRACEPTIVE AGENTS, ESTROGEN | CONTRACEPTIVE AGENTS, PROGESTIN | CONTRACEPTIVE AGENTS, SIDE EFFECTS | SEX FACTORS | NORETHINDRONE | ESTRADIOL | TREATMENT | Asia, Eastern | Asia | Developed Countries | Research Methodology | Demographic Factors | Population | Central Nervous System | Physiology | Biology | Diseases | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Population Characteristics | Estrogens | Hormones | Endocrine System | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health Document Number: 340167 |
| 12. Peer Reviewed Title: First chewable OC enters U.S. market. Source: Contraceptive Technology Update. 2004 Feb;25(2):[2] p.. Abstract: Successful pill-taking is an important component for women who use oral contraceptives (OCs). Inconsistent use and method discontinuation are estimated to account for approximately 20% of the annual 3.5 million annual unintended pregnancies in the United States. Will a chewable contraceptive aid in pill-taking compliance? The Food and Drug Administration (FDA) has just approved the first such product. Look for the launch of Ovcon 35 in late spring, says Katie MacFarlane, PharmD, vice president of marketing for Galen Holdings and Warner Chilcott, based in Rockaway, NJ. When a pill is reformulated into a chewable form, it must be flavored to mask the chalky taste of the active ingredient, says Jeff Worthington, managing director of food and pharmaceutical technologies at Cambridge, MA-based TIAX, an independent and privately held technology development and consulting firm that aids companies in developing palatable pharmaceuticals, nutritional products, foods, and beverages. (excerpt) Language: English Keywords: UNITED STATES OF AMERICA | CRITIQUE | ORAL CONTRACEPTIVES | USER COMPLIANCE | ADMINISTRATION AND DOSAGE | USFDA | PRODUCT APPROVAL | CONTRACEPTIVE EFFECTIVENESS | ETHINYL ESTRADIOL | NORETHINDRONE | PACKAGING | North America | Americas | Developed Countries | Contraceptive Methods | Contraception | Family Planning | Behavior | Drugs | Treatment | USPHS | Government Agencies | Organizations | Legislation | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Marketing | Economic Factors Document Number: 281814 |
| 13. Peer Reviewed Title: Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, and 17 beta-estradiol on vascular endothelial growth factor isomers 121 and 165 in Ishikawa cells. Author: Archer DF; Navarro FJ; Leslie S; Mirkin S Source: Fertility and Sterility. 2004 Jan;81(1):165-170. Abstract: Objective: To determine the effect of 17ß-E/2, levonorgestrel, medroxyprogesterone acetate, and norethindrone on the expression of vascular endothelial growth factor (VEGF) isoforms 121 and 165 in Ishikawa cells in vitro. Design: Prospective basic research study. Setting: Basic research laboratory. Patient(s): None. Ishikawa cells were cultured in vitro. After 24 hours’ incubation in serum-free media, 1.0, 0.1, and 0.01 µM concentrations of E2, levonorgestrel, medroxyprogesterone acetate, and norethindrone were added for a further 24 hours of incubation. Isolation and identification of VEGF isoforms 121 and 165 using semiquantitative polymerase chain reaction, gel electrophoresis, with ß-actin as an internal control. Estradiol stimulated VEGF isoforms 121 and 165. The progestins studied increased mRNA for VEGF isoforms 121 and 165 at all doses. Medroxyprogesterone acetate resulted in the greatest increase in both VEGF 121 and 165 compared with norethindrone and levonorgestrel. Estradiol and progestins increased VEGF 121 and 165 isoform mRNA in Ishikawa cells in vitro. We hypothesize that differences in VEGF expression may be associated with the irregular bleeding during progestin use in clinical situations. (author's) Language: English Keywords: UNITED STATES OF AMERICA | CLINICAL RESEARCH | COMPARATIVE STUDIES | PROSPECTIVE STUDIES | WOMEN | LEVONORGESTREL | MEDROXYPROGESTERONE ACETATE | NORETHINDRONE | ESTRADIOL | GENETICS | ENDOMETRIUM | Developed Countries | North America | Americas | Research Methodology | Studies | Demographic Factors | Population | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Estrogens | Hormones | Endocrine System | Physiology | Biology | Uterus | Genitalia, Female | Genitalia | Urogenital System Document Number: 190101 |
| 14. Title: The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone. Author: Hendrix CW; Jackson KA; Whitmore E; Guidos A; Kretzer R Source: Clinical Pharmacology and Therapeutics. 2004 May;75(5):464-475. Abstract: Isotretinoin is a known teratogen, and when it is prescribed to women of childbearing potential, 2 forms of contraception must be used, commonly including hormonal contraception. Although isotretinoin and estradiol are metabolized largely by cytochrome P450 (CYP) 3A4 and glucuronidation, the potential for clinical drug interaction, with subsequent pharmacodynamic impact, has not been evaluated. We enrolled 26 healthy women who were to receive isotretinoin for the treatment of severe, recalcitrant nodular acne and who were taking or planning to take oral contraceptives. The pharmacokinetics of ethinyl estradiol and norethindrone (INN, norethisterone) (the components of Ortho Novum 7/7/7; Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ) and pharmacodynamic assessments of oral contraceptive effectiveness (concentrations of serum progesterone, luteinizing hormone, and follicle-stimulating hormone) were determined on days 6 and 20 of 2 separate oral contraceptive cycles, before and during isotretinoin treatment. The addition of isotretinoin to the oral contraceptive regimen resulted in small and inconsistent, although statistically significant (P < .04), decreases in the concentrations of both ethinyl estradiol (9% decrease in area under the plasma concentration–time curve from time 0 to 24 hours after the dose on day 6) and norethindrone (11% decrease in maximum plasma concentration on day 20). Isotretinoin did not cause any statistically significant increases in pharmacodynamic markers, although a majority of women had increases in these measures. Although there was no correlation between isotretinoin (or metabolite) levels and oral contraceptive levels (P > .05), there was a correlation between progesterone level and oral contraceptive levels (P < .05). Variability was large for both pharmacokinetic measures (median coefficients of variation of 44%-69% [for each time point within a study period]) and pharmacodynamic measures (median coefficients of variation of 64%-114%). One woman in each study phase, one before and one during isotretinoin treatment, had a progesterone elevation consistent with possible ovulation. No serious or unexpected adverse events were observed. The small reduction in ethinyl estradiol and norethindrone levels associated with isotretinoin was not associated with any pharmacodynamic changes in our study. The combination of the teratogenic risk of isotretinoin and the large variability of and correlation between oral contraceptive levels and pharmacodynamic measures, however, strongly reinforces the necessity of additional contraceptive methods during concomitant administration of these drugs. (author's) Language: English Keywords: UNITED STATES OF AMERICA | NEW JERSEY | RESEARCH REPORT | CLINICAL RESEARCH | WOMEN | NORETHINDRONE | ETHINYL ESTRADIOL | CONTRACEPTIVE AGENTS, SIDE EFFECTS | ORAL CONTRACEPTIVES | ACNE | Developed Countries | North America | Americas | Research Methodology | Demographic Factors | Population | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Methods | Dermatitis | Diseases Document Number: 278049 |
| 15. Title: Effects of levonorgestrel, medroxyprogesterone acetate, norethindrone, progesterone, and 17 beta-estradiol on thrombospondin-1 mRNA in Ishikawa cells [letter] Author: Mirkin S; Archer DF Source: Fertility and Sterility. 2004 Jul;82(1):220-222. Abstract: Aberrant endometrial angiogenesis has been implicated in abnormal endometrial bleeding in users of progestin-only contraceptives. We believe that a possible cause is an underexpression of thrombospondi-1 (TSP-1). Progestins had less effect on TSP-1 mRNA compared to P, in Ishikawa cells, and this difference in TSP-1 expression by individual progestins may be associated with the irregular bleeding seen by women using progestin-only contraception. Long-acting progestin-only contraception is used by millions of women in more than 100 countries with an extremely high contraceptive efficacy. Irregular endometrial bleeding is a main disadvantage and results in significant personal distress and anxiety for users, which may result in their discontinuing use of these preparations. (excerpt) Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | GENETIC TECHNIQUES | WOMEN | LEVONORGESTREL | NORETHINDRONE | MEDROXYPROGESTERONE ACETATE | PROGESTERONE | ESTRADIOL | GENETICS | THROMBOSIS | METRORRHAGIA | CYTOLOGY | Developed Countries | North America | Americas | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Demographic Factors | Population | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Progestational Hormones | Hormones | Endocrine System | Physiology | Biology | Estrogens | Thromboembolism | Embolism | Vascular Diseases | Diseases | Bleeding | Signs and Symptoms Document Number: 277652 |
| 16. Peer Reviewed Title: Effect of hormonal emergency contraception on bleeding patterns. Author: Webb A; Shochet T; Bigrigg A; Loftus-Granberg B; Tyrer A Source: Contraception. 2004 Feb;69(2):133-135. Abstract: Spotting following the use of emergency contraception is not unusual, nor is anxiety in women waiting to see if the treatment has worked. It is not known whether such spotting should bring worry or relief. We, therefore, wished to see if there was any correlation between bleeding pattern and treatment outcome. Using data from a large multicenter efficacy trial, we examined bleeding patterns post-emergency contraception. The earlier in the cycle the pills were taken, the more likely the next bleed was to be early and the less likely it was to be on time. There was no observable difference in spotting rates between women who got pregnant and those who did not. The occurrence of spotting did not influence whether the next period was lighter or heavier. (author's) Language: English Keywords: UNITED KINGDOM | UNITED STATES OF AMERICA | RESEARCH REPORT | COMPARATIVE STUDIES | FAMILY PLANNING ACCEPTORS | WOMEN | EMERGENCY CONTRACEPTION | CONTRACEPTION FAILURE | BLEEDING | MENSTRUAL CYCLE | PREGNANCY, UNWANTED | NORETHINDRONE | Developed Countries | Europe, Western | Europe | North America | Americas | Studies | Research Methodology | Family Planning Programs | Family Planning | Demographic Factors | Population | Contraception | Contraceptive Usage | Signs and Symptoms | Diseases | Menstruation | Reproduction | Reproductive Behavior | Fertility | Population Dynamics | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 190266 |
| 17. Title: Use of progestins in male contraception. Author: Nieschlag E; Zitzmann M; Kamischke A Source: Steroids. 2003;68(10-13):965-972. Abstract: Hormonal male contraception aims at suppression of spermatogenesis to azoospermia or at least to severe oligoasthenozoospermia, incompatible with the ability to induce a pregnancy. The general principle of this approach is based on interference with the endocrine regulation of spermatogenesis, i.e. the suppression of gonadotropins. Since both FSH (through the Sertoli cell) and LH (through the Leydig cell and testosterone (T)) are required for normal spermatogenesis, both gonadotropins need to be suppressed as strongly as possible. In East Asian men this can be achieved with T alone (preferably in depot preparations such as T undecanoate) but only two-thirds of Caucasian men respond with adequate sperm suppression. Therefore, in Caucasian men additional substances such as GnRH antagonists or progestins are required to suppress the pituitary. Over the past 30 years many combinations of various T preparations with different progestins have been tested in clinical trials. Since self- applicable steroid combinations (e.g. oral levonorgestrel or desogestrel with transdermal T) showed low effectiveness, currently injections and implants are under clinical development. Long-acting intramuscular T esters (e.g. T undecanoate), T pellets or implants (e.g. MENT) are combined with injections of DMPA or noresthisterone enanthate or with implants containing levonorgestrel or etonogestrel. Acute side-effects of these combinations appear to be minimal and tolerable, long-term effects need to be investigated. (author's) Language: English Keywords: GERMANY | RESEARCH REPORT | CLINICAL TRIALS | MEN | TESTOSTERONE | CONTRACEPTIVE AGENTS, PROGESTIN | CONTRACEPTIVE AGENTS, MALE | NORETHINDRONE | SPERMATOGENESIS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | LEVONORGESTREL | MALE CONTRACEPTION | SPERMATOGENESIS BLOCKING AGENTS | Europe, Central | Europe | Developed Countries | Clinical Research | Research Methodology | Demographic Factors | Population | Androgens | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Reproduction Document Number: 277761 |
| 18. Title: All progestins are not created equal. Author: Stanczyk FZ Source: Steroids. 2003;68:879-890. Abstract: A variety of progestins are available for therapeutic use. It is convenient to classify them into those related in chemical structure to progesterone or testosterone. Progestins related to progesterone can be subdivided into pregnanes and 19-norpregnanes, whereas those related to testosterone can be subdivided into those with and without a 17-ethinyl group. 17-Ethinylated progestins consist of the families of norethindrone (estranes) and levonorgestrel (13-ethylgonanes). Progestins administered orally undergo extensive hepatic first pass metabolism primarily by reduction and conjugation, and in most instances, relatively high progestin doses are required for therapeutic use. There are limited reliable data on the pharmacokinetics of most progestins. Some progestins are prodrugs, requiring transformation prior to exhibiting progestational activity. Qualitative and quantitative tests utilizing either human or animal species have been used to establish progestin potency. However, profound differences in progestational activity are often observed between human and animal tissues. Also, there is a misconception about androgenicity of progestins due largely to extrapolation of data from rat studies to the human. Progestins differ widely in their chemical structures, structure–function relationships, metabolism, pharmacokinetics, and potencies; they are not created equal. (author's) Language: English Keywords: UNITED STATES OF AMERICA | WOMEN | LOW-DOSE PROGESTINS | CONTRACEPTIVE AGENTS, PROGESTIN | RESEARCH AND DEVELOPMENT | DESOGESTREL | LEVONORGESTREL | NORETHINDRONE | ESTROGENS | HORMONE REPLACEMENT THERAPY | ADMINISTRATION AND DOSAGE | North America | Americas | Developed Countries | Demographic Factors | Population | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Technology | Economic Factors | Hormones | Endocrine System | Physiology | Biology | Treatment | Drugs Document Number: 285271 |
| 19. Peer Reviewed Title: Pharmacokinetic interaction between nevirapine and ethinyl estradiol / norethindrone when administered concurrently to HIV-infected women. Author: Mildvan D; Yarrish R; Marshak A; Hutman HW; McDonough M Source: JAIDS. Journal of Acquired Immune Deficiency Syndromes. 2002 Apr 15;29(5):471-7. Abstract: This study aimed to determine the effect of nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK) of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive, and to assess the effects of EE/NET on the steady-state PK of NVP. 10 HIV-1 infected women underwent intensive PK sampling after single-dose administration of EE/NET (days 0-1). Oral NVP 200 mg once daily (days 2-15), followed by 200 mg twice daily (days 16-29), was added to background potent antiretroviral therapy. On day 30, intensive PK sampling was performed after concurrent administration of NVP 200 mg and a single dose of EE/NET. Concomitant administration of NVP at steady state with EE/NET resulted in a significant (29%) median reduction in the area under the plasma concentration time curve (AUC infinity) and a significant reduction in mean residence time (MRT) and half-life of EE. There was a significant (18%) median reduction in the AUC infinity for NET that was not associated with detectable change in NET C maximum, MRT, or half-life. Oral contraceptives should not be the primary method of birth control in women of childbearing potential who are treated with NVP. (author's) Language: English Keywords: CLINICAL RESEARCH | SAMPLING STUDIES | PREGNANT WOMEN | HIV INFECTIONS | ANTIVIRAL DRUGS | SAFETY | ETHINYL ESTRADIOL | NORETHINDRONE | Research Methodology | Studies | Population Characteristics | Demographic Factors | Population | Viral Diseases | Diseases | Drugs | Treatment | Public Health | Health | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin Document Number: 166510 |
| 20. Title: Evaluation of genotoxic potential of synthetic progestins-norethindrone and norgestrel in human lymphocytes in vitro. Author: Ahmad ME; Shadab GG; Azfer MA; Afzal M Source: Mutation Research. 2001 Jul 25;494(1-2):13-20. Abstract: The genotoxicity study of two widely used contraceptive synthetic progestins, i.e. norgestrel and norethindrone was carried out on human lymphocyte chromosomes using chromosomal aberrations (CA), sister chromatid exchanges (SCE) and cell growth kinetics as parameters. The study was carried out both in the presence as well as in the absence of metabolic activation (S/9 mix). The lymphocytes were exposed to three different concentrations of the drugs (20, 40 and 75µg/ml for norethindrone and 10, 25 and 50µg/ml for norgestrel) for three different durations (24, 48 and 72 h). The drug norethindrone was found to be non-genotoxic at any concentration and at any exposure duration either in the presence or in the absence of S/9 mix. But another drug norgestrel was found to affect the genetic material. It induces CA, SCE at significant level, and inhibits lymphocyte proliferation at 25 and 50µg/ml of concentrations only. In the presence of S9 mix the values obtained for CA, SCE and mitotic index (MI) were more significant. A time and dose relationship was also observed. It was concluded that norgestrel itself and possibly its metabolites are potent mutagens beyond a particular dose in human lymphocytes. (author's) Language: English Keywords: INDIA | RESEARCH REPORT | DRUGS | NORETHINDRONE | NORGESTREL | CHROMOSOME ABNORMALITIES | TOXICITY | IN VITRO | LABORATORY PROCEDURES | CYTOLOGIC EFFECTS | Asia, Southern | Asia | Developing Countries | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Neonatal Diseases and Abnormalities | Diseases | Physiology | Biology | Clinical Research | Research Methodology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses Document Number: 291383 |
| 21. Peer Reviewed Title: A prospective, controlled study of the effects of hormonal contraception on bone mineral density. Author: Berenson AB; Radecki CM; Grady JJ; Rickert VI; Thomas A Source: Obstetrics and Gynecology. 2001 Oct;98(4):576-82. Abstract: The aim was to compare the effect of depot medroxyprogesterone acetate (DMPA) and two types of oral contraceptives (OCs) on bone mineral density (BMD) among women 18-33 years of age with those not using hormonal contraception. Data from 155 women were analyzed. DMPA was administered to 33 women; 63 women who chose oral contraception were randomly assigned to receive either a norethindrone-containing pill (n = 28) or a desogestrel-containing pill (n = 35). 59 women who did not use hormonal contraceptive served as controls. Lumbar spine BMD was determined using dual-energy x-ray absorptiometry at baseline and after 12 months of contraceptive use. The authors analyzed method-related percent change in BMD while controlling for body mass index, calcium intake, exercise, and smoking. The authors had approximately 90% power to detect a 2.5% difference between any two groups. Users of DMPA experienced a mean BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37% loss (P = 0.01). Users of OCs generally demonstrated a gain (2.33% for norethindrone-containing pills, 0.33% for desogestrel-containing pills), which was different from controls among users of norethindrone-containing pills (P = 0.01), but not among users of desogestrel-containing pills (P = 0.99). Observed changes in BMD among DMPA users differed from women who used either type of pill (P < 0.002). DMPA has an adverse effect on BMD, in comparison with OCs or non-hormonal methods, when used for 12 months. Results must be interpreted cautiously until it is determined whether these effects endure or are reversible. (author's) Language: English Keywords: TEXAS | UNITED STATES OF AMERICA | RESEARCH REPORT | PROSPECTIVE STUDIES | CONTROL GROUPS | DEPO-PROVERA | ORAL CONTRACEPTIVES | NORETHINDRONE | DESOGESTREL | SKELETAL EFFECTS | Developed Countries | North America | Americas | Studies | Research Methodology | Medroxyprogesterone Acetate | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Methods | Physiology | Biology Document Number: 161106 |
| 22. Peer Reviewed Title: Multicenter, comparative study of cycle control, efficacy and tolerability of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol / 100 micrograms levonorgestrel and 20 micrograms ethinylestradiol / 500 micrograms norethisterone. Author: Endrikat J; Hite R; Bannemerschult R; Gerlinger C; Schmidt W Source: Contraception. 2001 Jul;64(1):3-10. Abstract: A comparison of cycle control, efficacy and tolerability of two oral contraceptive preparations containing 20 mcg ethinylestradiol (EE) combined with either 100 mcg levonorgestrel (LNG) (EE/LNG 20/100) or 500 mcg norethisterone (EE/NET 20/500) was conducted. These results were compared to a standard reference preparation, containing 30 mcg EE combined with 150 mcg (EE/LNG 30/150). Efficacy data from 8544 treatment cycles were obtained from 767 women. Good cycle control and effective contraception was achieved with the two LNG preparations, however, the cycle control results were less favorable with EE/NET 20/500. The cumulative incidence of women with at least one episode of intermenstrual bleeding from cycles 2-7 (primary target variable) was 43.9% for EE/LNG 20/100, 72.7% for EE/NET 20/500, and 15.7% for the standard EE/LNG 30/150. The difference between the two 20 mcg of EE preparations, which favored EE/LNG 20/100, was statistically significant (p = 0.001). The overall spotting rates (cycles 1-13) were 9.3% for EE/LNG 20/100, 21.7% for EE/NET 20/500, and 3.3% for the standard EE/LNG 30/150. Amenorrhea was reported in 7.1% (EE/LNG 20/100), 20.6% (EE/NET 20/500), and 0.9% (standard EE/LNG 30/150), respectively. Intermenstrual bleeding episodes were shorter with EE/LNG 20/100 and EE/LNG 30/150 of the 13 treatment cycles. The study Pearl indices were 0.9 for EE/LNG 20/100, 1.9 for EE/NET 20/500, and 0.0 for EE/LNG 30/150. All three treatments were well tolerated. However, tolerability was somewhat less favorable with EE/NET 20/500. A total of 160 women prematurely discontinued the study for various reasons (EE/LNG 20/100: 7%; EE/NET 20/500: 18%; EE/LNG 30/150: 4%). The overall adverse event incidence rate during the trial was low in all groups. Blood pressure remained largely unaffected. 13 serious adverse events were recorded for all treatment groups, all but one were assessed as not related to the treatments. There were no remarkable treatment related differences in mean body weight throughout the study and the laboratory values were largely unaffected in all three treatment groups. (author's) Language: English Keywords: GERMANY | RESEARCH REPORT | COMPARATIVE STUDIES | PROSPECTIVE STUDIES | ORAL CONTRACEPTIVES, LOW-DOSE | ETHINYL ESTRADIOL | LEVONORGESTREL | NORETHINDRONE | THEORETICAL EFFECTIVENESS | Europe, Central | Europe | Developed Countries | Studies | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Contraceptive Effectiveness Document Number: 160394 |
| 23. Peer Reviewed Title: A-ring reduced metabolites of 19-nor synthetic progestins as subtype selective agonists for ER alpa. Author: Larrea F; García-Becerra R; Lemus AE; Garcí GA; Pérez-Palacios G Source: Endocrinology. 2001 Sep;142(9):3791-3799. Abstract: It has previously been demonstrated that 19-nor contraceptive progestins undergo in vivo and in vitro enzyme-mediated A-ring double bond hydrogenation. Bioconversion of 19-nor progestins to their corresponding tetrahydro derivatives results in the loss of progestational activity and acquisition of estrogenic activities and binding to the ER. Herein, we report subtype-selective differences in ligand binding and transcriptional potency of nonphenolic synthetic 19-nor derivates between ERa and ERß. In this study, we have examined both ER- and PR-mediated transcriptional activity of a number of A-ring chemically reduced derivatives of norethisterone and Gestodene. Double bond hydrogenation decreased the transcriptional potency of norethisterone and Gestodene through both PR isoforms with a 100- to 1,000-fold difference, respectively. In terms of the effects of norethisterone and Gestodene and their corresponding 5a-dihydro (5a-norethisterone and 5a-Gestodene), or 3a,5a-tetrahydro or 3ß,5a-tetrahydro derivatives (3a,5a-norethisterone/3a,5a-Gestodene and 3ß,5a-norethisterone/3ß,5a-Gestodene, respectively) on estrogen-mediated transcriptional regulation, the 3ß,5a-tetrahydro derivatives of both norethisterone and Gestodene showed the highest induction when HeLa cells were transiently transfected with an expression vector for ERa. This activity could be inhibited with tamoxifen. These compounds did not activate gene transcription via ERß, and none of them showed antagonistic activities through either ER subtype. The 3ß,5a-tetrahydro derivatives of both norethisterone and Gestodene were active in other cells in addition to HeLa cells and activated reporter expression through the oxytocin promoter. In summary, two ERa selective agonists have been identified. These compounds, with ERa vs. ERß selective agonist activity, may be useful in evaluating the distinct role of these receptors as well as in providing useful insights into ER action. (author's) Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | CONTRACEPTIVE AGENTS, PROGESTIN | METABOLIC EFFECTS | ESTROGENS | PROGESTERONE | HORMONE RECEPTORS | GENETICS | PHYSIOLOGY | NORETHINDRONE | Developed Countries | North America | Americas | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Biology | Hormones | Endocrine System | Progestational Hormones | Membrane Proteins Document Number: 295744 |
| 24. Peer Reviewed Title: The emerging use of the 20-microgram oral contraceptive. Author: Poindexter A Source: Fertility and Sterility. 2001 Mar;75(3):457-65. Abstract: The aim was to highlight studies that investigated the efficacy, safety, and tolerability of low-dose oral contraceptives (OCs) containing 20 mcg of ethinyl estradiol (EE) and to discuss the use of these low-dose contraceptives in women from adolescence to menopause and the noncontraceptive health benefits likely to be afforded by low-dose contraceptives. Relevant literature was identified by searching MEDLINE and EMBASE. Other sources were located by consulting the bibliographies of the material collected from Medline and EMBASE. Sources for additional information included documents from the US Food and Drug Administration and the Physicians' Desk Reference (54th edition). The current lowest available dose of EE used for OCs in the US is 20 mcg. Formulations with 20 mcg of EE are efficacious and have a low incidence of estrogen-related side effects. Since this lowest effective EE dose inhibits ovarian activity, 20 mcg of EE should also provide the noncontraceptive health benefits of OCs. Both contraceptive and noncontraceptive benefits of OCs are available to most women from adolescence to menopause without complications. (author's) Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | ORAL CONTRACEPTIVES, LOW-DOSE | ETHINYL ESTRADIOL | LEVONORGESTREL | DESOGESTREL | GESTODENE | NORETHINDRONE | SAFETY | Developed Countries | North America | Americas | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Public Health | Health Document Number: 155631 |
| 25. Peer Reviewed Title: Comparative effects of Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension) and Ortho-Novum 7/7/7 oral contraceptive (norethindrone / ethinyl estradiol triphasic) on lipid profiles. Author: Cromie MA; Maile MH; Wajszczuk CP Source: Contraception. 2000 Jan;61(1):51-9. Abstract: As part of a 60-week, open-label, nonrandomized, parallel, controlled study comparing a monthly contraceptive injection containing medroxyprogesterone acetate (MPA) 25 mg and estradiol cypionate (E2C) 5 mg (Lunelle[TM] Monthly Contraceptive Injection) and a norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum[R] 7/7/7), a longitudinal examination of lipid profiles was conducted. Lipid parameters were assessed at screening and at weeks 20, 40, and 60 (or the final visit) in 114 women using MPA/E2C and 93 using NET/EE (lipid analysis population). Extra blood samples were obtained at weeks 21, 22, and 23 in 61 MPA/E2C users and 51 NET/EE users (index-cycle analysis population) to investigate lipid changes during one cycle of use. In the index-cycle population, median changes from screening to week 60 showed a decrease in apolipoprotein (apo) A-I and A-II in both groups. MPA/E2C users had a decrease in total cholesterol (C), total triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with maintenance of the total C/HDL-C ratio. NET/EE users showed an increase in total C and LDL-C, with no change in HDL-C or the total C/HDL-C ratio. Within the index cycle (weeks 20-23), median changes in lipid values in both MPA/E2C and NET/EE users were generally greatest during the first week after the injection or the start of the pill pack. The results of the first longitudinal examination of serum lipids in US women using MPA/E2C confirm earlier findings in women in other countries. However, a direct comparison of the effects of MPA/E2C and NET/EE on lipid profiles was not possible in the study because of its design and because of the baseline and pharmacokinetic/pharmacodynamic differences between the two contraceptive groups. The results of this analysis showed that, although overall lipid values decreased, including a significant decrease in HDL cholesterol, the maintenance of the total-C/HDL-C ratio suggests that the effect of MPA/E2C on lipid parameters may not negatively affect CVD risk over 1 year of use. However, these results warrant further investigation, given the nature of the trial. (author’s) Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | CLINICAL RESEARCH | LONGITUDINAL STUDIES | COMPARATIVE STUDIES | ESTRADIOL | MEDROXYPROGESTERONE ACETATE | INJECTABLES | ORAL CONTRACEPTIVES, PHASIC | NORETHINDRONE | ETHINYL ESTRADIOL | LIPIDS | Developed Countries | North America | Americas | Research Methodology | Studies | Estrogens | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Methods | Oral Contraceptives, Combined | Oral Contraceptives | Contraceptive Agents, Estrogen Document Number: 148993 |
| 26. Peer Reviewed Title: Bleeding patterns of women using Lunelle monthly contraceptive injections (medroxyprogesterone acetate and estradiol cypionate injectable suspension) compared with those of women using Ortho-Novum 7/7/7 (norethindrone / ethinyl estradiol triphasic) or other oral contraceptives. Author: Garceau RJ; Wajszczuk CJ; Kaunitz AM Source: Contraception. 2000 Dec;62(6):289-95. Abstract: Persistent and/or unpredictable bleeding is a common reason for discontinuation of hormonal contraceptive methods. An open-label, nonrandomized, parallel, controlled study compared the efficacy, safety, and cycle control of the new, highly efficacious monthly injectable contraceptive containing 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate (E2C) (MPA/E2C) (Lunelle Monthly Contraceptive Injection) with that of the frequently used norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum 7/7/7). This report directly compares the bleeding patterns of women on MPA/E2C to those of women on NET/EE and untreated women. Overall, breakthrough bleeding occurred less frequently in women using MPA/E2C than in women using NET/EE (p Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | COMPARATIVE STUDIES | MENSTRUATION DISORDERS | INJECTABLES | MEDROXYPROGESTERONE ACETATE | ESTRADIOL | ORAL CONTRACEPTIVES, PHASIC | NORETHINDRONE | ETHINYL ESTRADIOL | CONTRACEPTIVE EFFECTIVENESS | SAFETY | Developed Countries | North America | Americas | Studies | Research Methodology | Diseases | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Estrogens | Hormones | Endocrine System | Physiology | Biology | Oral Contraceptives, Combined | Oral Contraceptives | Contraceptive Agents, Estrogen | Public Health | Health Document Number: 155839 |
| 27. Peer Reviewed Title: Efficacy, cycle control, and safety of two triphasic oral contraceptives: Cyclessa (desogestrel / ethinyl estradiol) and Ortho-Novum 7/7/7 (norethindrone / ethinyl estradiol). A randomized clinical trial. Author: Kaunitz AM Source: Contraception. 2000 May;61(5):295-302. Abstract: The contraceptive efficacy, cycle control, and safety of a new low-dose, triphasic desogestrel/ethinyl estradiol oral contraceptive (OC) (CTR 77, Cyclessa) was compared to that of a marketed, triphasic norethindrone/ethinyl estradiol OC (Ortho-Novum 7/7/7). Two identical multicenter, open-label, randomized, parallel group, comparative Phase III 6-cycle trials were designed to each enroll 4200 healthy women. The combined comparative data for Cyclessa versus Ortho-Novum 7/7/7 for both studies are reported here. Cyclessa and Ortho-Novum 7/7/7 had comparable contraceptive efficacy. Despite a lower ethinyl estradiol dose (25 vs. 35 mcg/day), the Cyclessa group had significantly improved cycle control in comparison to the Ortho-Novum 7/7/7 group for presence of a withdrawal bleed (p = 0.001), lack of early withdrawal bleed (p = 0.01), and breakthrough bleeding/spotting (p = 0.001). For each of the months of the study, the incidence of breakthrough bleeding/spotting was lower in the Cyclessa group than the Ortho-Novum 7/7/7 group (breakthrough bleeding, p = 0.006; breakthrough spotting, p = 0.001). The incidence of other adverse events was similar among treatment groups, an observation that supports the safety of both formulations. There was significantly less weight gain (p = 0.0002) and less increase in the body mass index (p = 0.0002) in the Cyclessa group. The contraceptive efficacy and safety of Cyclessa is comparable to Ortho-Novum 7/7/7. Cyclessa provides significantly improved cycle control with no weight gain. (author's) Language: English Keywords: RESEARCH REPORT | CLINICAL RESEARCH | COMPARATIVE STUDIES | ORAL CONTRACEPTIVES, LOW-DOSE | CONTRACEPTIVE EFFECTIVENESS | MENSTRUATION | BLEEDING | SAFETY | DESOGESTREL | ETHINYL ESTRADIOL | NORETHINDRONE | Research Methodology | Studies | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Reproduction | Signs and Symptoms | Diseases | Public Health | Health | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen Document Number: 151173 |
| 28. Peer Reviewed Title: A pre-coital pill? A preliminary in vitro study. Author: Kovacs GT; Hendricks J; Summerbell D; Baker HW Source: British Journal of Family Planning. 2000 Jul;26(3):165-6. Abstract: The use of the progestogen-only pill as a "pre-coital contraceptive" was tested by in vitro studies of sperm-mucus interaction. The results suggest that a single tablet of levonorgestrel 30 mcg, or norethisterone 350 mcg, was effective in preventing sperm migration in the cervical mucus about 12 hours later. This suggests that the progestogen-only pill may be effective as a "morning before pill". (author's) Language: English Keywords: SUMMARY REPORT | LEVONORGESTREL | NORETHINDRONE | SPERM TRANSPORT INHIBITION | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Inhibition of Fertilization | Contraceptive Mode of Action Document Number: 155504 |
| 29. Title: Understanding oral contraceptive progestins: classification of estranes and gonanes. Source: Contraception Report. 1999 Jan;9(6):[4] p.. Abstract: Progestins in oral contraceptives (OCs) have been the focus of intense scrutiny over the past decade. The terminology used to classify OC progestins, however, has become confusing. Terms such as "new," "newer," "second-generation" and "third-generation" have been used under no standard guidelines. One misclassification, in particular, has been in grouping norethindrone and levonorgestrel, so-called second-generation progestins, together. Norethindrone and levonorgestrel belong to two distinct classes of synthetic progestins. Norethindrone and other progestins that metabolize to norethindrone are estranes. Levonorgestrel and related compounds are gonanes. Estranes and gonanes exhibit different metabolic characteristics that prohibit including them in the same class. This article is the first in a series that will examine different aspects of oral contraceptive progestins. In future issues, we will explore the evidence regarding the pharmacokinetics of progestins, metabolic effects, and whether any progestin is, in fact, "androgenic." (excerpt) Language: English Keywords: UNITED STATES OF AMERICA | TERMINOLOGY | CLASSIFICATION | WOMEN | HEALTH PERSONNEL | CONTRACEPTIVE AGENTS, PROGESTIN | ORAL CONTRACEPTIVES | NORETHINDRONE | LEVONORGESTREL | CONTRACEPTION RESEARCH | North America | Americas | Developed Countries | Research Methodology | Demographic Factors | Population | Delivery of Health Care | Health | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Methods Document Number: 312829 |
| 30. Title: The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive. Author: Barditch-Crovo P; Trapnell CB; Ette E; Zacur HA; Coresh J; Rocco LE; Hendrix CW; Flexner C Source: CLINICAL PHARMACOLOGY AND THERAPEUTICS.. 1999 Apr;65(4):428-38. Abstract: The relative effects of rifampin and rifabutin (a related rifamycin) on the pharmacokinetics and pharmacodynamics of ethinyl estradiol (EE) and norethindrone were evaluated in a prospective, randomized, double-blinded crossover study in 12 premenopausal women who were on a stable oral contraceptive regimen that contained 35 mcg EE and 1 mg norethindrone. Subjects were randomized to receive 14 days of rifampin or rifabutin from days 7 through 21 of their menstrual cycle. After a 1-month washout period (only the oral contraceptives were taken), subjects were crossed over to the other rifamycin. Findings showed that rifampin significantly decreased the mean area under the plasma concentration-time curve from time 0 to 24 hours [AUC (0-24)] of EE and the mean AUC (0-24) of norethindrone. Rifabutin significantly decreased the mean AUC (0-24) of EE and the mean AUC (0-24) of norethindrone. The effect of rifampin was significantly greater than rifabutin on each AUC (0-24). Despite these changes, subjects did not ovulate (as determined by progesterone concentrations) during the cycle in which either rifamycin was administered. Levels of mean follicle-stimulating hormone increased 69% after rifampin. This study suggests that rifampin (600 mg daily) was a more important inducer of EE and norethindrone clearance than rifabutin, but none of these agents were able to reverse the suppression of ovulation done by oral contraceptives. Language: English Keywords: MARYLAND | UNITED STATES OF AMERICA | RESEARCH REPORT | NORETHINDRONE | ETHINYL ESTRADIOL | ORAL CONTRACEPTIVES | FOLLICLE STIMULATING HORMONE | PROGESTERONE | DRUGS | North America | Americas | Developed Countries | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Methods | Gonadotropins, Pituitary | Gonadotropins | Hormones | Endocrine System | Physiology | Biology | Progestational Hormones | Treatment Document Number: 146696 |
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