2.  Peer Reviewed Title: Menstrual blood loss in women using the frameless FibroPlant LNG-IUS. Author: Andrade A; Wildemeersch D Source: Contraception. 2009 Feb;79(2):134-8. Abstract: BACKGROUND: This study was conducted to report on a menstrual blood loss (MBL) study and iron stores in women with and without heavy menstrual bleeding using the frameless FibroPlant levonorgestrel-releasing intrauterine system (LNG-IUS) for contraception. STUDY DESIGN: An open, prospective, noncomparative MBL study, using FibroPlant releasing 14 mcg of LNG/day for contraception. MBL was assessed by the quantitative alkaline hematin (QAH) technique. RESULTS: The MBL study was conducted in 40 heavy and normally menstruating Brazilian women seeking contraception. MBL was reduced from a mean baseline menstrual volume of 29.7 mL to a mean volume of 1.5 mL after 24 months, while ferritin values increased from a mean value of 31.1 ng/mL (at baseline) to a mean level of 72.5 ng/mL (after 24 months of use). Differences were highly significant (p<.0005). There were no significant differences between those who had normal menstrual bleeding and the heavy bleeders. The heavy bleeders had comparable MBL to thenormal bleeders 3 months after insertion, and by 24 months post-insertion, their ferritin levels were comparable to those of the normal bleeders. Amenorrhea occurred in 80% of women out of 40 after 24 months of use. No pregnancies were recorded. CONCLUSION: The LNG-IUS is effective in reducing MBL in normally menstruating women as well as in women with heavy menstrual bleeding. The authors agree with the recommendations by the UK National Institute for Clinical Effectiveness and the new Finnish guidelines for heavy menstrual bleeding that the LNG-IUS should be positioned as first-line treatment prior to endometrial ablation or hysterectomy. Language: English Keywords: BRAZIL | RESEARCH REPORT | CLINICAL RESEARCH | PROSPECTIVE STUDIES | EPIDEMIOLOGIC METHODS | WOMEN IN DEVELOPMENT | MENSTRUATION | SERUM IRON LEVEL | IUD, HORMONE RELEASING | LEVONORGESTREL | MENORRHAGIA | TIME FACTORS | AMENORRHEA | PREVALENCE | CONTRACEPTIVE EFFECTIVENESS | South America, Eastern | South America | Latin America | Americas | Developing Countries | Research Methodology | Studies | Economic Development | Economic Factors | Reproduction | Hemic System | Physiology | Biology | IUD | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Menstruation Disorders | Diseases | Population Dynamics | Demographic Factors | Population | Measurement Document Number: 331016 |
| 3. Peer Reviewed Title: Ovarian activity and safety of a novel levonorgestrel/ethinyl estradiol continuous oral contraceptive regimen. Author: Archer DF; Kovalevsky G; Ballagh SA; Grubb GS Source: Contraception. 2009 Sep;80(3):245-53. Abstract: BACKGROUND: A continuous regimen of oral levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg was evaluated for inhibition of ovulation, time to return to ovulation after stopping treatment and safety. STUDY DESIGN: This open-label study was conducted in healthy women aged 18-35 years. Ovulation was documented before treatment, and then participants received oral tablets containing LNG 90 mcg/EE 20 mcg to be taken continuously for three 28-day intervals. Ovarian activity was assessed three times per week during the treatment period with transvaginal ultrasound scans and measurements of serum 17beta-estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone concentrations. Safety assessments included physical examinations, laboratory evaluations and adverse event records. RESULTS: Thirty-seven of the 58 subjects who received treatment met predefined criteria for efficacy analysis. No on-treatment ovulations occurred in the efficacy or intent-to-treat population. There was evidence of ovulation within 37 days of stopping treatment for 46 (98%) of 47 subjects evaluated posttreatment. The final subject with a history of polycystic ovarian syndrome ovulated by Day 66. The safety profile observed during this 84-day continuous regimen was similar to that seen with other low-dose oral contraceptives administered in a cyclic regimen. CONCLUSIONS: The continuous LNG/EE regimen completely inhibited ovulation, with little evidence of follicular development and with rapid return of ovulatory capacity after stopping treatment. Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | WOMEN | ORAL CONTRACEPTIVES | LEVONORGESTREL | ETHINYL ESTRADIOL | SAFETY | ULTRASONICS | OVARIAN EFFECTS | TREATMENT | Developed Countries | North America | Americas | Demographic Factors | Population | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Public Health | Health | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Ovary | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology Document Number: 342575 |
| 4. Title: Emergency contraception: how does it work? Author: Baird DT Source: Reproductive Biomedicine Online. 2009;18 Suppl 1:32-6. Abstract: Emergency (or post-coital) contraception is any substance or device that is used to prevent pregnancy after unprotected intercourse. Currently used hormonal methods of emergency contraception (high-dose combined oral contraceptive pill or levonorgestrel) prevent about 50-80% of pregnancies. Research has demonstrated that these methods inhibit the midcycle surge of LH from the pituitary and, if given at least 2 days before ovulation, ovulation is delayed or prevented. Ovulation still occurs if administration is delayed until ovulation is imminent. Biological data that suggest that the most likely mode of action is by preventing fertilization are supported by the clinical observation that the greater the interval between coitus and administration the greater the chance of pregnancy. There are no data supporting the view that levonorgestrel can impair the development of the embryo or prevent implantation. In contrast, other very effective methods of emergency contraception, such as mifepristone and intrauterine devices, can also inhibit implantation. Language: English Keywords: UNITED KINGDOM | RESEARCH REPORT | EMERGENCY CONTRACEPTION | IUD | RU-486 | LEVONORGESTREL | CONTRACEPTIVE EFFECTIVENESS | Developed Countries | Europe, Western | Europe | Contraception | Family Planning | Contraceptive Methods | Hormone Antagonists | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 330739 |
| 5. Title: Genetic counseling for teratogenic risk due to exposure to medications: 89 pregnancies conceived during oral contraceptive use. Author: Belli S; Mazzola S; Luongo R; Barcella L; Alushi B Source: American Journal of Medical Genetics. Part A. 2009 Jun 5; Abstract: Congenital malformations are relatively frequent (2% of the general population) but only a small proportion of them can be ascribed to medication exposure during pregnancy. Nevertheless, for the purposes of accurate prenatal diagnosis, monitoring and research, is it important to offer teratology counseling to patients exposed to drugs. There are approximately 20 medications currently on the market that have been universally acknowledged as teratogenic. At the current state of the art, exposure of early embryos to oral contraceptives is not considered teratogenic. Oral contraceptive use may be continuous (estrogen and progesterone or progesterone alone) or emergency (levonorgestrel is the only drug authorized in Italy). Like all drugs, oral contraceptives have a therapeutic failure rate, which means that a number of women on oral contraceptives conceive each year and request genetic counseling about teratogenic effects. During the period 1998-2006 at our genetics clinic we received 89 requests for counseling regarding teratogenic risk due to oral contraceptives. Our study of these patients confirms an absence of teratogenic risk for pregnancies occurring during oral contraceptive use. Teratology counseling was useful to reassure the mothers about the low risk (in the case of oral contraceptive use alone), since only 12 women chose to terminate pregnancy. Language: English Keywords: ITALY | RESEARCH REPORT | GENETICS | COUNSELING | EXPOSURE | ORAL CONTRACEPTIVES | CONTRACEPTIVE AGENTS, ESTROGEN | PROGESTERONE | LEVONORGESTREL | CONGENITAL ABNORMALITIES | RISK FACTORS | PREGNANCY | Developed Countries | Europe, Southern | Europe | Biology | Clinic Activities | Program Activities | Programs | Organization and Administration | Health | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Female | Contraceptive Agents | Progestational Hormones | Hormones | Endocrine System | Physiology | Contraceptive Agents, Progestin | Neonatal Diseases and Abnormalities | Diseases | Reproduction Document Number: 341602 |
| 6. Peer Reviewed Title: Developments and challenges in emergency contraception. Author: Black KI Source: Best Practice and Research: Clinical Obstetrics and Gynaecology. 2009 Apr;23(2):221-231. Abstract: Emergency contraception (EC) methods, available in oral and intrauterine forms, seek to prevent pregnancy after unprotected intercourse or contraceptive failure. Levonorgestrel EC is more effective and has fewer side effects than the previously used combined oral hormonal method; the Yuzpe regimen. In recent years, levonorgestrel has increased in use, and has become available over the counter in pharmacies in many countries. compared with oral methods, the copper intra-uterine device offers greater protection against unplanned pregnancy but requires a clinical consultation. The much hoped for potential of EC methods to reduce unintended pregnancy is yet to be demonstrated at population level. Language: English Keywords: GLOBAL | RESEARCH REPORT | CLINICAL RESEARCH | WOMEN | EMERGENCY CONTRACEPTION | LEVONORGESTREL | RU-486 | IUD | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, SIDE EFFECTS | PHARMACY DISTRIBUTION | IUD, COPPER RELEASING | NAUSEA | VOMITING | FATIGUE | PAIN | Research Methodology | Demographic Factors | Population | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Hormone Antagonists | Hormones | Endocrine System | Physiology | Biology | Contraceptive Methods | Oral Contraceptives | Contraceptive Safety | Safety | Public Health | Health | Nonclinical Distribution | Distributional Activities | Program Activities | Programs | Organization and Administration | Signs and Symptoms | Diseases Document Number: 341506 |
| 7. Peer Reviewed Title: Effect of sexual intercourse on the absorption of levonorgestrel after vaginal administration of 0.75 mg in Carraguard gel: a randomized, cross-over, pharmacokinetic study. Author: Brache V; Croxatto H; Kumar N; Sitruk-Ware R; Cochon L; Schiappacasse V; Sivin I; Munoz C; Maguire R; Faundes A Source: Contraception. 2009 Feb;79(2):150-4. Abstract: BACKGROUND: The Population Council studied a pre-coital contraceptive microbicide vaginal product containing levonorgestrel (LNG) as active component and Carraguard gel as a vehicle (Carra/LNG gel) for couples who engage in occasional unplanned intercourse. The objective of this study was to evaluate the effect of sexual intercourse after vaginal application of Carra/LNG gel on serum levels of LNG in women and to assess LNG absorption by the male partner. STUDY DESIGN: This was a randomized, cross-over, pharmacokinetic study including an abstinence arm and an arm in which couples engaged in sexual intercourse between 2 and 4 h after gel application. In each study arm, each woman received a single application of Carra/LNG gel (0.75 mg in 4 mL gel) followed by serial blood samples taken at 0, 1, 2, 4, 8, 24 and 48 h after gel application for LNG measurements. In the intercourse arm, LNG was measured in blood samples taken from the male partner before intercourse and at 4, 8 and 24 h after gel application in the female partner. RESULTS: Time concentration curves for serum LNG levels showed a mean C(max) of 7.8+/-5.5 and 8.3+/-5.7 nmol/L, a mean T(max) of 6.2+/-5.9 and 7.5+/-5.7, and comparable area under the curve for the intercourse and abstinence arm, respectively. Pharmacokinetic parameters presented large variability between subjects, but excellent reproducibility within each subject. LNG was undetectable in 10 out of 12 male partners. CONCLUSION: Sexual intercourse does not appear to interfere with vaginal absorption of LNG after application of a Carra/LNG gel. A vaginal pre-coital contraceptive gel is feasible. Language: English Keywords: DOMINICAN REPUBLIC | RESEARCH REPORT | CLINICAL RESEARCH | WOMEN IN DEVELOPMENT | SEXUAL PARTNERS | SEXUAL INTERCOURSE | PHYSIOLOGY | LEVONORGESTREL | VAGINAL GEL | MICROBICIDES | TIME FACTORS | CONTRACEPTIVE EFFECTIVENESS | EMERGENCY CONTRACEPTION | Developing Countries | Caribbean | Americas | Research Methodology | Economic Development | Economic Factors | Sex Behavior | Behavior | Reproduction | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Vaginal Spermicides | Contraceptive Methods | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Population Dynamics | Demographic Factors | Population Document Number: 331015 |
| 8. Title: Influence of transdermal rotigotine on ovulation suppression by a combined oral contraceptive. Author: Braun M; Elshoff JP; Andreas JO; Muller LI; Horstmann R Source: British Journal of Clinical Pharmacology. 2009 Sep;68(3):386-94. Abstract: AIMS: To assess the influence of the transdermally applied dopamine agonist rotigotine on ovulation suppression by a combined oral contraceptive (0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel) in a randomized, double-blind crossover study in 40 healthy females. METHODS: Treatment A consisted of the combined oral contraceptive for 28 days plus rotigotine for the first 13 days (2 mg (24 h)(-1) on days 1-3, 3 mg (24 h)(-1) maintenance dose thereafter). During treatment B, subjects received matching placebo patches instead of rotigotine. Pharmacodynamic parameters (progesterone, oestradiol, luteinizing hormone, and follicle stimulating hormone serum concentrations), pharmacokinetic parameters for ethinyloestradiol/levonorgestrel and rotigotine, and safety and tolerability of the treatment were assessed. RESULTS: Progesterone serum concentrations remained below 2 ng ml(-1) in all subjects during the luteal phase. Median serum concentrations of all other pharmacodynamic parameters were similar during both treatments. Pharmacokinetic parameters C(max,ss) and AUC(0,24 h)(ss) at steady state were similar with or without co-administration of rotigotine for both ethinyloestradiol and levonorgestrel with geometric mean ratios close to 1 and 90% confidence intervals within the acceptance range of bioequivalence (0.8, 1.25): C(max,ss) 1.05 (0.93, 1.19), AUC(0,24 h)(ss) 1.05 (0.9, 1.22) for ethinyloestradiol; C(max,ss) 1.01 (0.96, 1.06), AUC(0,24 h)(ss) 0.98 (0.95, 1.01) for levonorgestrel. Mean plasma concentrations of unconjugated rotigotine remained stable throughout the patch-on period (day 13). CONCLUSIONS: Concomitant administration of 3 mg (24 h)(-1) transdermal rotigotine had no impact on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing 0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel, suggesting that the dopamine agonist does not influence contraception efficacy. Language: English Keywords: SOUTH AFRICA | SUMMARY REPORT | WOMEN | ORAL CONTRACEPTIVES, COMBINED | LEVONORGESTREL | ETHINYL ESTRADIOL | ADMINISTRATION AND DOSAGE | CONTRACEPTIVE SAFETY | TREATMENT | Developing Countries | Africa, Southern | Africa, Sub Saharan | Africa | Demographic Factors | Population | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Drugs | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Safety | Public Health Document Number: 342711 |
| 10. Peer Reviewed Title: Insertion of intrauterine contraceptives immediately following first- and second-trimester abortions. Author: Drey EA; Reeves MF; Ogawa DD; Sokoloff A; Darney PD; Steinauer JE Source: Contraception. 2009 May;79(5):397-402. Abstract: BACKGROUND: The study was conducted to assess the continuation and patient satisfaction with intrauterine contraception (IUC) insertion immediately after elective abortion in the first and second trimesters in an urban, public hospital-based clinic. STUDY DESIGN: A cohort of 256 women who elected to have insertion of a copper-T IUC (CuT380a) or a levonorgestrel-releasing IUC (LNG-IUC) were followed postoperatively by phone calls or chart review to evaluate satisfaction and continuation with the method. RESULTS: Of our 256 subjects, 123 had first-trimester abortions and 133 had second-trimester abortions (14 or more weeks). Median time to follow-up was 8 weeks (range 7-544 days). Nineteen discontinuations occurred: eight (6.5%, 95% CI 2.8-12.4%) following first-trimester and 11 (8.3%, 95% CI 4.2-14.3%) following second-trimester abortion (p=.6). Five women reported expulsion; one (0.8%, 95% CI 0.0-4.4%) in the first-trimester group and four (3.0%, 95% CI 0.8-7.5%) in the second-trimester group. (p=.4) Seven infections resulting in discontinuation occurred (2.7%, 95% CI 1.1-5.6%); none were positive for gonorrhea or chlamydia at time of insertion. No perforations occurred. Nearly all (93.8%) of the women were satisfied with IUC. Rates of satisfaction between women after first- and second-trimester abortions were equal. CONCLUSION: In an urban clinic, IUC has high initial continuation and high patient satisfaction when inserted immediately following either first- or second-trimester abortions. Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | CONTRACEPTIVE PREVALENCE SURVEYS | WOMEN | URBAN POPULATION | POSTABORTAL PROGRAMS | UTERUS | PREGNANCY, SECOND TRIMESTER | IUD, COPPER RELEASING | CONTRACEPTION CONTINUATION | SATISFACTION | IUD, HORMONE RELEASING | LEVONORGESTREL | PREGNANCY, FIRST TRIMESTER | IUD EXPULSION | Developed Countries | North America | Americas | Family Planning Surveys | Family Planning | Demographic Factors | Population | Population Characteristics | Family Planning Programs | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | Pregnancy | Reproduction | IUD | Contraceptive Methods | Contraception | Contraceptive Usage | Psychological Factors | Behavior | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 330942 |
| 11. Peer Reviewed Title: Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity. Author: Edelman AB; Carlson NE; Cherala G; Munar MY; Stouffer RL; Cameron JL; Stanczyk FZ; Jensen JT Source: Contraception. 2009 Aug;80(2):119-27. Abstract: BACKGROUND: This study was conducted to determine whether increased body mass index (BMI) affects oral contraceptive (OC) pharmacokinetics and suppression of hypothalamic-pituitary-ovarian (HPO) axis activity. STUDY DESIGN: Ovulatory reproductive-age women with normal weight (BMI <25 kg/m(2); n=10) and with obesity (BMI >30 kg/m(2); n=10) received OCs for two cycles (prospective cohort). Subjects were admitted for two 48-h inpatient stays at the beginning and end of the hormone-free interval. Ethinyl estradiol and levonorgestrel (LNG) levels were evaluated during both inpatient stays. Gonadotropin pulsatility (follicle-stimulating hormone and luteinizing hormone) was measured during the second inpatient stay. Estradiol (E(2)) and progesterone (P) were measured daily during inpatient stays and twice per week in Cycle 2. RESULTS: BMI was greater in the obese compared to the normal-BMI group [37.3 kg/m(2) (SD, 6.0) vs. 21.9 kg/m(2) (SD, 1.6); p<.05]. The LNG half-life was significantly longer in the obese group (52.1+/-29.4 vs. 25.6+/-9.3 h, p<.05), which correlated with a lower maximum LNG concentration on Cycle 2, Day 1 [1.9 ng/mL (SD, 0.5) vs. 2.5 ng/mL (SD, 0.7)] and a longer time to reach steady state (10 vs. 5 days) in obese women. There were no significant differences in volume of distribution between groups. LH pulse parameters did not differ statistically between groups but trended toward greater HPO activity in the obese group. Additionally, more obese (6/10 vs. 3/10 normal BMI, p>.05) women exhibited E(2) levels consistent with development of a dominant follicle and P levels consistent with ovulation (2/10 vs. 1/10) during Cycle 2. CONCLUSIONS: Compared to women with normal BMI, obese women exhibit differences in OC pharmacokinetics that are associated with greater HPO activity. Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | PROSPECTIVE STUDIES | WOMEN | OBESITY | ORAL CONTRACEPTIVES, COMBINED | CONTRACEPTION FAILURE | ETHINYL ESTRADIOL | LEVONORGESTREL | GONADOTROPINS, PITUITARY | LABORATORY PROCEDURES | TIME FACTORS | Developed Countries | North America | Americas | Studies | Research Methodology | Demographic Factors | Population | Body Weight | Physiology | Biology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Usage | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Gonadotropins | Hormones | Endocrine System | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Population Dynamics Document Number: 342308 |
| 12. Peer Reviewed Title: Prevention of tamoxifen induced endometrial polyps using a levonorgestrel releasing intrauterine system long-term follow-up of a randomised control trial. Author: Gardner FJ; Konje JC; Bell SC; Abrams KR; Brown LJ; Taylor DJ; Habiba M Source: Gynecologic Oncology. 2009 Sep;114(3):452-6. Abstract: OBJECTIVES: In a RCT, we have previously shown that the levonorgestrel intrauterine system (LNG-IUS, Mirena) produces a decidual response protecting the endometrium at one year follow-up. We here report on the long-term follow-up of this group of women, to test the hypothesis that a LNG-IUS could prevent the pro-proliferative uterine responses of tamoxifen for up to 4.5 years. METHODS: A randomised-controlled trial of postmenopausal women who had taken at least one year of adjuvant tamoxifen therapy. RESULTS: One hundred twenty-two women were recruited. Nine were found to be ineligible after randomisation. The average duration of follow-up was 26.25 months (IQR 14.5-36 months) in the surveillance group and 24.2 months (IQR 13.75-32.5 months) in the LNG-IUS group. Women with LNG-IUS in situ at the time of final assessment had decidualised endometrium, and no polyps. In the surveillance group new polyps arose in 8 cases. There were 3 new polyps in the group initially randomised to LNG-IUS, one in a patient who did not have the device inserted and 2 occurred in patients following the removal of the LNG-IUS. Univariate Cox proportional hazards regression models identified only endometrial thickness at trial entry as a statistically significant variable (HR 1.12, 95% CI 1.02 to 1.22, p=0.01) for the development of polyps. CONCLUSION: This study confirms that LNG-IUS induces benign endometrial changes and prevents endometrial polyps but only during its use in women taking tamoxifen. Endometrial thickness is a risk factor for the development of polyps. Language: English Keywords: UNITED KINGDOM | RESEARCH REPORT | CONTROL GROUPS | CLIENTS | BREAST CANCER | TAMOXIFEN | ENDOMETRIAL EFFECTS | IUD, HORMONE RELEASING | LEVONORGESTREL | HYSTEROSCOPY | ULTRASONICS | Developed Countries | Europe, Western | Europe | Research Methodology | Program Activities | Programs | Organization and Administration | Cancer | Neoplasms | Diseases | Fertility Agents | Reproductive Control Agents | Family Planning | Endometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | IUD | Contraceptive Methods | Contraception | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Endoscopy | Physical Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health Document Number: 342402 |
| 13. Peer Reviewed Title: Ectopic pregnancy following levonorgestrel emergency contraception: a case report. Author: Ghosh B; Dadhwal V; Deka D; Ramesan CK; Mittal S Source: Contraception. 2009 Feb;79(2):155-7. Abstract: Use of levonorgestrel as emergency contraception is a safe and effective measure to prevent unwanted pregnancy. However, ectopic gestation in case of failure is a known risk. Access to levonorgestrel without a prescription in many countries has made it impossible to estimate the exact incidence of this potential adverse event. Thus, spontaneous reporting of cases serves to alert physicians to this possibility. We present a case of ectopic pregnancy following use of levonorgestrel emergency contraception. To our knowledge, this is the first case report from India following introduction of levonorgestrel emergency contraception in 2001. Language: English Keywords: INDIA | RESEARCH REPORT | EMERGENCY CONTRACEPTION | LEVONORGESTREL | CONTRACEPTIVE SAFETY | PREGNANCY, ECTOPIC | PREGNANCY, UNWANTED | Developing Countries | Asia, Southern | Asia | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Safety | Public Health | Health | Pregnancy Complications | Diseases | Reproductive Behavior | Fertility | Population Dynamics | Demographic Factors | Population Document Number: 329608 |
| 14. Peer Reviewed Title: Use of the Levonorgestrel-IUS in the treatment of menorrhagia: assessment of quality of life in Turkish users. Author: Gorgen H; Api M; Akca A; Cetin A Source: Archives of Gynecology and Obstetrics. 2009 Jun;279(6):835-40. Abstract: OBJECTIVE: The aim of the present study was to measure the treatment of menorrhagia and health-related quality of life (QoL) in Levonorgestrel-releasing intrauterine system (LNG-IUS) in Turkish women. MATERIALS AND METHODS: We recruited 66 premenopausal women, aged 26-55 years, who had sought care in the previous year for menorrhagia. All patients were asked to complete a visual analog scale (VAS) form regarding pelvic pain, sexual life (libido) and general feeling of health. Patients filled the VAS form before LNG-IUS insertion and after 6 months. RESULTS: After the 6-month visit, PBAC score was condirebly decreased (p < 0.001). Six (10%) of the 60 patients PBAC score was higher than 75. VAS score for pelvic pain decreased from baseline to 6-month follow-up (4.32-3.55), and the libido and general feeling of health increased (4.27-4.95 and 3.47-6.87, respectively). CONCLUSION: The LNG-IUS device in the trearment of menorrhagia has cost effective, less side effects and increse in the QoL. Language: English Keywords: TURKEY | RESEARCH REPORT | CLINICAL RESEARCH | CLIENTS | MENORRHAGIA | TREATMENT | IUD, HORMONE RELEASING | LEVONORGESTREL | IUD SIDE EFFECTS | QUALITY OF LIFE | PAIN | SEX BEHAVIOR | Europe, Southeastern | Europe | Developing Countries | Research Methodology | Program Activities | Programs | Organization and Administration | Menstruation Disorders | Diseases | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | IUD | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Social Welfare | Economic Factors | Signs and Symptoms | Behavior Document Number: 342109 |
| 15. Peer Reviewed Title: Serum levonorgestrel levels and endometrial thickness during extended use of the levonorgestrel-releasing intrauterine system. Author: Hidalgo MM; Hidalgo-Regina C; Bahamondes MV; Monteiro I; Petta CA; Bahamondes L Source: Contraception. 2009 Jul;80(1):84-9. Abstract: BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is a contraceptive method approved for five years of use. However, there is some evidence that its life span may be longer. The aim of the study was to evaluate serum levonorgestrel (LNG) and estradiol (E(2)) levels and endometrial thickness every 6 months from 7 to 8 1/2 years after insertion. STUDY DESIGN: At the end of the approved 5-year life span, no replacement devices were available; therefore, 86 women were allowed to retain the same device for a further 2 years. At the 7-year follow-up visit, the women who consented were again allowed to retain the same device for a further 18 months and were followed-up at six-monthly intervals. At each visit, vaginal sonography was performed to measure endometrial thickness, and a blood sample was taken to measure LNG and E(2). RESULTS: Eighty-four months after insertion, 67 women aged 34.3+/-0.8 years (mean+/-SEM) (range, 25-49 years) returned for follow-up. Mean+/-SEM LNG levels decreased from an initial 253+/-27 pg/mL (range, 86-760) during the first 2 months following insertion to 137+/-12 (range, 23-393) at 84 months and 119+/-9 pg/mL (range, 110-129) at 102 months of use (+/-SEM). At 84 months of use, mean+/-SEM endometrial thickness was 2.8+/-0.1 mm, increasing to 3.8+/-0.5 mm at 102 months of use. The incidence of amenorrhea decreased from 41.8% at 84 months to 31.5% at 102 months of use. No correlation was found between LNG levels and bleeding patterns; however, a weak correlation was found between high body mass index (kg/m(2)), high weight, and low serum LNG levels. E(2) levels were similar to those of the follicular phase of the menstrual cycle of regularly menstruating women. CONCLUSIONS: During extended use of the LNG-IUS, serum LNG levels were nearly half those found in the first 2 months of use (Wilcoxon signed rank test); serum E(2) levels were normal. Despite the very thin endometrium, menstrual bleeding was reinstated in many cases. At the end of its 5-year life span, there is a window for changing the LNG-IUS, and physicians and users should not be concerned about delaying replacement of the device for a short time beyond the approved life span; however, maintaining the same device long after its approved life span cannot be recommended. Language: English Keywords: BRAZIL | RESEARCH REPORT | FAMILY PLANNING ACCEPTORS | IUD, HORMONE RELEASING | LEVONORGESTREL | ESTRADIOL | ENDOMETRIUM | TIME FACTORS | ULTRASONICS | HEMATOLOGIC TESTS | AMENORRHEA | INCIDENCE | MENSTRUATION | South America, Eastern | South America | Latin America | Americas | Developing Countries | Family Planning Programs | Family Planning | IUD | Contraceptive Methods | Contraception | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Estrogens | Hormones | Endocrine System | Physiology | Biology | Uterus | Genitalia, Female | Genitalia | Urogenital System | Population Dynamics | Demographic Factors | Population | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Menstruation Disorders | Diseases | Measurement | Research Methodology | Reproduction Document Number: 342787 |
| 16. Peer Reviewed Title: The emergency contraceptive pill rescheduled: a focus group study of women's knowledge, attitudes and experiences. Author: Hobbs M; Taft AJ; Amir LH Source: Journal of Family Planning and Reproductive Health Care. 2009 Apr;35(2):87-91. Abstract: BACKGROUND AND METHODOLOGY: The levonorgestrel-containing emergency contraceptive pill (ECP), amongst other strategies, has the potential to assist in reducing unintended pregnancy and abortion rates. Since the rescheduling of the ECP in January 2004 to over-the-counter (OTC) status from pharmacies in Australia, there is little information about Australian women's ECP knowledge, attitudes or practice. The aim of the study was to explore Australian women's knowledge of, attitudes towards and experiences of using the ECP, particularly since it has been available OTC. This paper reports a qualitative study using six focus groups, which were conducted between February and June 2007 in four Australian states with 29 women aged 16-29 years. RESULTS: Participants had a lack of specific knowledge about the ECP. Most were positive about the ECP being available OTC, however some expressed concerns about younger women misusing it. Women's experiences obtaining the ECP from the pharmacy were both positive and negative. Most women said they would use the ECP again if required and would recommend it to a friend. Pharmacists were seen as important suppliers of the ECP but women felt it was not their role to provide advice about contraception or sexually transmitted infections. DISCUSSION AND CONCLUSIONS: The findings from this study confirm views from other studies, which suggest that although women have some concerns in relation to OTC supply of the ECP, they believe that the deregulation of the ECP is a positive step. The data also suggest that women need to be provided with more information and education about the ECP. Language: English Keywords: AUSTRALIA | RESEARCH REPORT | FOCUS GROUPS | WOMEN | EMERGENCY CONTRACEPTION | KNOWLEDGE | ATTITUDES | LEVONORGESTREL | CONTRACEPTIVE USAGE | CONTRACEPTIVE AVAILABILITY | AGE FACTORS | Oceania | Developed Countries | Data Collection | Research Methodology | Demographic Factors | Population | Contraception | Family Planning | Sociocultural Factors | Psychological Factors | Behavior | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Population Characteristics Document Number: 330948 |
| 17. Peer Reviewed Title: Term pregnancy with intraperitoneal levonorgestrel intrauterine system: a case report and review of the literature. Author: Hopkins MR; Agudelo-Suarez P; El-Nashar SA; Creedon DJ; Rose CH; Famuyide AO Source: Contraception. 2009 Apr;79(4):323-7. Abstract: BACKGROUND: The risk of adverse effects of fetal exposure to the levonorgestrel intrauterine system (LNG-IUS) has not been established. STUDY DESIGN: In this case report and literature review, we describe a pregnant patient with an intraperitoneal LNG-IUS and the subsequent maternal and neonatal outcomes. A systematic literature search was performed to identify similar clinical reports. The MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, Web of Science and Scopus databases were searched from inception through March 2007. RESULTS: The pregnancy progressed uneventfully and culminated in the elective cesarean delivery of a full-term healthy boy. Of the 35 pregnancies identified in the literature review (34 pregnancies with intrauterine LNG-IUS and 1 term delivery with intraperitoneal LNG-IUS), congenital anomalies were reported in 2 infants (6%). CONCLUSIONS: Fetal exposure to LNG-IUS is associated with a low frequency of congenital anomalies. Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | LITERATURE REVIEW | ADOLESCENTS | ADOLESCENT PREGNANCY | LEVONORGESTREL | IUD, HORMONE RELEASING | PREGNANCY | CONTRACEPTION | PREGNANCY OUTCOMES | Developed Countries | North America | Americas | Youth | Age Factors | Population Characteristics | Demographic Factors | Population | Reproductive Behavior | Fertility | Population Dynamics | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Family Planning | IUD | Contraceptive Methods | Reproduction Document Number: 341632 |
| 18. Peer Reviewed Title: Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons. Author: Hubacher D; Lopez L; Steiner MJ; Dorflinger L Source: Contraception. 2009 Aug;80(2):113-8. Abstract: BACKGROUND: Many women want a lengthy duration of contraception but are wary of the menstrual changes from depot medroxyprogesterone acetate (DMPA). A subdermal levonorgestrel (LNG) implant may be a reasonable alternative. However, information on menstrual changes from these methods has not been summarized and compared in an easy-to-understand form. STUDY DESIGN: We systematically reviewed the published literature on these contraceptives to find research that used menstrual diaries and standard World Health Organization definitions. We attempted to find information on amenorrhea, number of bleeding or spotting episodes, number of bleeding or spotting days and normal patterns, as reported in four consecutive 90-day reference periods. RESULTS: We found 16 published articles meeting our criteria and involving diaries of up to 1600 DMPA users and 2300 LNG implant users. We were able to compare the two methods on only three outcomes. For DMPA use, the weighted prevalence of amenorrhea at successive 90-day periods was 12%, 25%, 37% and 46%. The comparable estimates for the LNG implant were 11%, 13%, 9% and 13%. Levonorgestrel implant users experienced a higher average number of bleeding or spotting days compared to DMPA users, but this average was similar to what is expected naturally. At 12 months, normal menstrual patterns were experienced by 23% of LNG implant users compared to 11% of DMPA users. CONCLUSIONS: Like most hormonal contraception, LNG implants usually produce menstrual changes; however, the changes do not appear to deviate from normal patterns as much as the changes from DMPA. Understanding these differences and other method attributes might help women make an informed choice about which contraceptive to use. Language: English Keywords: GLOBAL | LITERATURE REVIEW | COMPARATIVE STUDIES | CONTRACEPTIVE IMPLANTS | LEVONORGESTREL | DEPO-PROVERA | CONTRACEPTIVE AGENTS, SIDE EFFECTS | MENSTRUATION DISORDERS | AMENORRHEA | Studies | Research Methodology | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Medroxyprogesterone Acetate | Diseases Document Number: 342394 |
| 19. Peer Reviewed Title: Spontaneous breakage and expulsion of a stem fragment of levonorgestrel intrauterine system (Mirena) following duplicate insertion [letter] Author: Jindal S; Sharma SS; Ikomi A Source: Archives of Gynecology and Obstetrics. 2009 Jan;279(1):95-7. Abstract: BACKGROUND: Removal and changing an intra-uterine device (IUD) involves good history taking, a proper examination and appropriate experience in fitting IUDs. CASE: We present a case of a woman who had two insertions of the levonorgestrel intrauterine system (LNG-IUS) which was diagnosed only at hysteroscopy when she presented with the spontaneous expulsion of a vertical stem of one of the devices. CONCLUSION: This is a unique case where two LNG-IUS were inserted in error and hence it teaches the clinicians the importance of good training and being aware of the possibility of the missing thread which deserves further investigations especially when such cases are encountered in a busy general practice. Language: English Keywords: UNITED KINGDOM | RESEARCH REPORT | CASE STUDIES | WOMEN | IUD EXPULSION | HYSTEROSCOPY | LEVONORGESTREL | INSERTION | SURGICAL ERROR | ABORTION, SPONTANEOUS | Developed Countries | Europe, Western | Europe | Studies | Research Methodology | Demographic Factors | Population | IUD | Contraceptive Methods | Contraception | Family Planning | Endoscopy | Physical Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Treatment | Surgery | Pregnancy Complications | Diseases Document Number: 329580 |
| 20. Title: Editorial fair play and emergency contraception [letter] Author: Kauffman RP Source: Southern Medical Journal. 2009 May;102(5):551. Abstract: With pleasure and a sense of academic responsibility, I accepted an invitation to submit an editorial addressing a paper by Galvin and Fagan in the January 2009 issue of Southern Medical Journal. Subsequently, I read with interest a thoughtful second editorial which addressed not only the investigation by Galvin and Fagan but also commented on my editorial. A second perspective is fair enough, of course, given that emergency contraception (EC) is viewed with controversy by some. In the spirit of robust debate, I offer the following comments that I would have included in my original editorial had the opportunity been granted. Jones and Stammers ventured that I "bravely risk tautology" by stating that EC does not act at the postimplantation level. In response, I would ask that they be able to offer reasonable evidence-based data that it does. Instead, they provided only speculation. Considerable evidence supports inhibition of ovulation as EC's mechanism of action,while implantation prevention remains unsubstantiated. Nonhuman primate and murine models have failed to demonstrate a postfertilization effect by levonorgestrel-containing EC. While I agree that human data would be welcomed, this task will prove methodologically and statistically daunting given that most fertilized ova do not implant in vivo under normal conditions. The American College of Obstetricians and Gynecologists (ACOG) Practice Guideline (on which my statement concerning EC's mechanism of action was plainly referenced) is based on best available medical evidence. ACOG recommendations are regularly updated when better evidence arises. One could only wish for the same equanimity from governmental regulatory agencies cued by ideological communities. Jones and Stammers quibble with the meaning of "efficacy," but their contention that EC is ineffective is little more than cherry-picking the literature. The recent Cochrane Database Systematic Review of the 81 randomized, controlled trials concluded that EC does work although mifepristone is more effective than levonorgestrel (Plan B®) or the Yuzpe method. In fact, the Cochrane Plain Language Summary concludes, "Mifepristone and levonorgestrel are very effective with few adverse effects . . .." Confounders, some known and others more obscure, may explain the relative lack of benefit of EC in some published trials. Scientific debate is healthy and necessary, and it is imperative that medical journals assure that the discussion is sound and bidirectional. (full-text) Language: English Keywords: UNITED STATES OF AMERICA | TEXAS | CRITIQUE | EMERGENCY CONTRACEPTION | LEVONORGESTREL | RU-486 | CONTRACEPTIVE USE-EFFECTIVENESS | Developed Countries | North America | Americas | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Hormone Antagonists | Hormones | Endocrine System | Physiology | Biology | Contraceptive Effectiveness Document Number: 341207 |
| 21. Peer Reviewed Title: Levonorgestrel-releasing intrauterine system and endometrial ablation in heavy menstrual bleeding: a systematic review and meta-analysis. Author: Kaunitz AM; Meredith S; Inki P; Kubba A; Sanchez-Ramos L Source: Obstetrics and Gynecology. 2009 May;113(5):1104-16. Abstract: OBJECTIVE: To compare the effects of the levonorgestrel intrauterine system and endometrial ablation in reducing heavy menstrual bleeding. DATA SOURCES: Medline and EMBASE were searched online using Ovid up to January 2009, as well as the reference lists of published articles, to identify randomized controlled trials comparing the levonorgestrel intrauterine system with endometrial ablation in the treatment of heavy menstrual bleeding. METHODS OF STUDY SELECTION: This systematic review and meta-analysis was restricted to randomized controlled trials in which menstrual blood loss was reported using pictorial blood loss assessment chart scores. TABULATION, INTEGRATION, AND RESULTS: Six randomized controlled trials that included 390 women (levonorgestrel intrauterine system, n=196; endometrial ablation, n=194) were retrieved. Three studies pertained to first-generation endometrial ablation (manual hysteroscopy) and three to second-generation endometrial ablation (thermal balloon). Study characteristics and quality were recorded for each study. Data on the effect of treatment on pictorial blood loss assessment chart scores were abstracted, integrated with meta-analysis techniques, and presented as weighted mean differences. Both treatment modalities were associated with similar reductions in menstrual blood loss after 6 months (weighted mean difference, -31.96 pictorial blood loss assessment chart score [95% confidence interval (CI), -65.96 to 2.04]), 12 months (weighted mean difference, 7.45 pictorial blood loss assessment chart score [95% CI, -12.37 to 27.26]), and 24 months (weighted mean difference, -26.70 pictorial blood loss assessment chart score [95% CI, -78.54 to 25.15]). In addition, both treatments were generally associated with similar improvements in quality of life in five studies that reported this as an outcome. No major complications occurred with either treatment modality in these small trials. CONCLUSION: Based on the meta-analysis of six randomized clinical trials, the efficacy of the levonorgestrel intrauterine system in the management of heavy menstrual bleeding appears to have similar therapeutic effects to that of endometrial ablation up to 2 years after treatment. Language: English Keywords: UNITED KINGDOM | RESEARCH REPORT | CLINICAL TRIALS | WOMEN | BLEEDING | LEVONORGESTREL | IUD | ENDOMETRIAL EFFECTS | CONTRACEPTIVE METHOD ACCEPTABILITY | CONTRACEPTIVE USE-EFFECTIVENESS | Developed Countries | Europe, Western | Europe | Clinical Research | Research Methodology | Demographic Factors | Population | Signs and Symptoms | Diseases | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Methods | Endometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | Contraceptive Usage | Contraceptive Effectiveness Document Number: 341342 |
| 22. Peer Reviewed Title: The effect of levonorgestrel-releasing intrauterine device on menorrhagia in women taking anticoagulant medication after cardiac valve replacement. Author: Kilic S; Yuksel B; Doganay M; Bardakci H; Akinsu F; Uzunlar O; Mollamahutoglu L Source: Contraception. 2009 Aug;80(2):152-7. Abstract: BACKGROUND: This study was conducted to evaluate the effect of levonorgestrel-releasing intrauterine devices (LNG-IUDs) on menorrhagia in patients receiving anticoagulant therapy after cardiac valve replacement. STUDY DESIGN: Forty women with menorrhagia who underwent cardiac valve replacement and were taking anticoagulant medication were enrolled in the study. The women were randomly divided into two groups: LNG-IUDs were inserted into 20 women in Group 1 over the first 3 days of menstrual bleeding, while the women in Group 2 were followed without any intervention. The activated partial thromboplastin time, prothrombin time, international normalized ratio, hematocrit level, hemoglobin level, ferritin level and pictorial bleeding assessments for the quantity of menstrual bleeding were recorded. RESULTS: Three months after insertion of LNG-IUDs, the women in Group 1 had a significant decrease in blood loss and higher hemoglobin, hematocrit and ferritin values. No difference was detected for these parameters in the control group at the third and sixth months of the study. Coagulation parameters did not differ between the two groups. CONCLUSION: LNG-IUDs can be considered as an effective non-surgical treatment for menorrhagia in women receiving anticoagulant therapy after cardiac valve replacement. Language: English Keywords: TURKEY | RESEARCH REPORT | CONTROL GROUPS | CLIENTS | IUD, HORMONE RELEASING | LEVONORGESTREL | MENORRHAGIA | CARDIOVASCULAR EFFECTS | POSTOPERATIVE PROCEDURES | DRUGS | BLOOD COAGULATION EFFECTS | Europe, Southeastern | Europe | Developing Countries | Research Methodology | Program Activities | Programs | Organization and Administration | IUD | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Menstruation Disorders | Diseases | Physiology | Biology | Surgery | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Hematological Effects | Hemic System Document Number: 342392 |
| 23. Peer Reviewed Title: Differential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time. Author: Labied S; Galant C; Nisolle M; Ravet S; Munaut C; Marbaix E; Foidart JM; Frankenne F Source: Human Reproduction. 2009 Jan;24(1):113-21. Abstract: BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective contraceptive and has many non-contraceptive health benefits. However, it is commonly associated with irregular endometrial bleeding. Metalloproteinases contribute to extracellular matrix (ECM) remodelling and regulate bleeding during the menstrual cycle. Enhanced metalloproteinase expression participates in the pathogenesis of breakthrough bleeding. Thus the objective of this study was to compare matrix metalloproteinase (MMP) expression in endometrium during luteal phase and in short-term (1 month) and long-term (> or =6 months) LNG-IUS users. METHODS: MMP expression was analysed by semi-quantitative RT-PCR and immunohistochemistry. Gelatinase activity was determined by gelatin zymography. RESULTS: MMP-1, -2, -3, -7, -9 and -12 mRNAs levels were increased, whereas that of MMP-26 was decreased in the endometrium of LNG-IUS users. MMP-1, -2, -3, -7 and -9 were localized by immunohistochemistry in all biopsies inthe short-term group but in only 0-27% in the control group. The incidence of positive immunostaining for MMP-2 and -3 decreased significantly in the long-term compared with short-term LNG-IUS users. MMP-26 was localized in all biopsies from the control group but in only 14 and 25% from the short- and long-term LNG-IUS groups, respectively. In both LNG groups, the numbers of macrophages (the major source of MMP-12) was increased. CONCLUSIONS: MMP-1, active MMP-2, MMP-3, MMP-7, MMP-9 and MMP-12 are more prevalent in the short-term LNG-IUS group, suggesting their important contribution to ECM breakdown and transient bleeding. The decrease in the percentage of women expressing MMP-2 and -3 might contribute to the decreased occurrence of unwanted spotting and bleeding in long-term LNG-IUS users. Language: English Keywords: BELGIUM | RESEARCH REPORT | CLINICAL RESEARCH | GENETIC TECHNIQUES | CASE CONTROL STUDIES | WOMEN | LEVONORGESTREL | IUD, HORMONE RELEASING | METRORRHAGIA | ENDOMETRIUM | PROTEINS | GENETICS | CYTOCHEMICAL EFFECTS | Developed Countries | Europe, Western | Europe | Research Methodology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Studies | Demographic Factors | Population | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | IUD | Contraceptive Methods | Bleeding | Signs and Symptoms | Diseases | Uterus | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | Cytologic Effects Document Number: 330074 |
| 24. Title: IUS producing a TAC [letter] Author: Lipscombe SL Source: Journal of Family Planning and Reproductive Health Care. 2009 Apr;35(2):132. Abstract: I recently saw a very unusual patient in whom an intrauterine system (IUS) appeared to produce a trigeminal autonomic cephalgia (TAC). The patient, a 39-year-old woman, was fortunate never to have had a headache until the events reported here. In early 2007, the patient started to complain of severe menorrhagia. Her periods were heavy and lasted 14 days, and necessitated the use of 15-20 sanitary pads a day. Tranexamic acid 1000 mg qds was tried initially for 8 weeks but the heavy bleeding continued. Next a therapeutic trial of norethisterone 5 mg tds was tried for many months resulting in a mild improvement. In desperation, the patient was referred to a gynaecologist who felt that the next step was to insert a levonorgestrel-releasing IUS. This was duly done. Within 6 hours of inserting the IUS the attacks started. All the patient's attacks (averaging 5-7 attacks/day) were similar. All were left sided and lasted 15-30 minutes. An attack started with pain to the side of the left eye that the patient described as unbearable, like the worst toothache ever. Associated with the pain was profuse tearing mainly from the left eye, although the pain was so bad the patient also cried with her right eye. Her palpabral fissure narrowed, her nose ran and her eye became pink. Her face felt strange and numb though painful. Touching her face, or brushing her hair or her teeth, did not trigger an attack. The attacks continued daily for 4 weeks until the patient came to see me. As she entered the room, an attack started. Following the attack I removed the patient's IUS very easily and gave her a zolmitriptan nasal spray in case she had further attacks. I arranged to see her 7 days later, at which time she appeared to be a completely different person. She had suffered one further attack some 6 hours after the IUS was removed and so had used the nasal spray. After this her attacks had totally stopped. At that clinic visit, in order to help her menorrhagia, which still raged, I started the patient on norethisterone again. Eighteen months later she is still totally free of attacks, and although her bleeding is still very heavy, she is not prepared to even consider allowing me to reinsert an intrauterine device/system, with or without hormones. She says the pain was the worst pain she could ever imagine and as a result she would never, even for the purposes of research, have an IUS inserted again. This woman appeared to develop a TAC, which approximated most closely to a cluster headache, though some attacks lasted only 15 minutes. It might be argued that it was not the IUS itself, but the hormone present in the IUS, which triggered the attacks, however this seems unlikely. The patient had already had very large doses of progestogen prior to IUS insertion with no ill effects and has also had large doses following IUS removal. The progesterone dose in the IUS is effective locally and is unlikely to have reached a high level after only 6 hours. Conversely, if the problem were the hormone in the IUS, its removal would be unlikelyto cause the hormone level to decrease significantly in 6 hours. In summary, on the face of it this would appear to be a simple case of a woman having an IUS inserted and developing a TAC, which was rapidly cured by removing the device. I would be delighted to discover if any of the Journal's readers have observed a similar case. (full-text) Language: English Keywords: UNITED KINGDOM | SUMMARY REPORT | CASE HISTORIES | CLIENTS | IUD, HORMONE RELEASING | LEVONORGESTREL | IUD SIDE EFFECTS | HEADACHE | MENORRHAGIA | Developed Countries | Europe, Western | Europe | Data Collection | Research Methodology | Program Activities | Programs | Organization and Administration | IUD | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Signs and Symptoms | Diseases | Menstruation Disorders Document Number: 341645 |
| 25. Title: Comparison of the content, uniformity of dosage units and dissolution rate of triphasic oral contraceptives from two pharmaceutical factories. Author: Liu H; Li Y; Liu JP Source: Journal of Reproduction and Contraception. 2009 Jun;20(2):123-129. Abstract: Objective: To compare the content, uniformity of dosage units and dissolution rate of triphasic oral contraceptives from two pharmaceutical factories A and B. Methods: A High Performance Liquid Chromatography (HPLC) method for the simultaneous determination of levonorgestrel and ethinylestradiol was used. The content of levonorgestrel (LNG) was monitored by an UV detector at 247nm, while ethinylestradiol (EE) was monitored by fluorescence detector with the excitation of 285 nm and emission wavelengths of 310 nm. The dissolution test was performed using the paddle method. Results The content of levongestrel (LNG) and ethinylestradiol (EE) in product A was within 100.5%-122.4% while product B within 120.6%-140.9%. The uniformity value of dosage units of tablets from two factories was more than 15. The dissolution rate of tables from two factories was more than 60% within 60 min. Conclusion Only the content of product A was in the ±25% range of label claim. The uniformity of two products was not up to standard. The dissolution rate of the tablets from two products met the requirement of ChP2005. Language: English Keywords: CHINA | RESEARCH REPORT | COMPARATIVE STUDIES | LABORATORY PROCEDURES | LEVONORGESTREL | ETHINYL ESTRADIOL | ORAL CONTRACEPTIVES | ADMINISTRATION AND DOSAGE | Asia, Eastern | Asia | Developing Countries | Studies | Research Methodology | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Methods | Drugs | Treatment Document Number: 339904 |
| 26. Title: Emergency contraception: Knowledge, attitude and prescription practice among doctors in different specialties in Hong Kong. Author: Lo SS; Kok WM; Fan SY Source: Journal of Obstetrics and Gynaecology Research. 2009 Aug;35(4):767-74. Abstract: Aim: Few studies have evaluated doctors' knowledge, attitudes and practices as regards emergency contraception (EC). Some studies have reported inadequate knowledge, bias and wrong prescriptions by doctors. This article compares the prescription pattern, attitude and knowledge of EC in Hong Kong doctors in different specialties. Methods: Questionnaires were mailed to family physicians, obstetrician-gynecologists and doctors working in family planning clinics to ascertain their attitudes to EC. Those who provided EC described the types of EC used, whether drugs were given in advance and answered a 12-question knowledge test. Those who did not provide EC stated why. Results: A total of 443 completed questionnaires were analyzed: 70.9% of doctors agreed that the benefits of EC outweigh its risks and 61.2% agreed that doctors should discuss it with clients. Advanced provision was supported by 54.2% of doctors but reduced to 32.5% if the target client was a girl aged 16 or below. Even fewer doctors (40.2%) supported the over-the-counter sales of EC pills. In the knowledge test, family planning doctors scored 10.45 out of 12 and obstetrician-gynecologists in private practice had the lowest score of 6.08. Family planning doctors used levonorgestrel pills while private family physicians and obstetrician-gynecologists used Yuzpe. Among 352 doctors who provided EC, only 21.7% of private family physicians and 15.9% of private obstetrician-gynecologists prescribed it in advance. Conclusions: Only doctors working in family planning clinics were competent in their knowledge of emergency contraception and up to date with current practice. Although half of the doctors supported advanced provision, few implemented it. Most doctors did not support advanced provision to young girls nor the over-the-counter sales of EC pills. Language: English Keywords: HONG KONG | RESEARCH REPORT | KAP SURVEYS | PHYSICIANS | EMERGENCY CONTRACEPTION | PRESCRIPTIONS | CONTRACEPTIVE DISTRIBUTION | OBSTACLES | LEVONORGESTREL | ETHINYL ESTRADIOL | IUD | QUESTIONNAIRES | AGE FACTORS | Developed Countries | Asia, Eastern | Asia | Surveys | Sampling Studies | Studies | Research Methodology | Health Personnel | Delivery of Health Care | Health | Contraception | Family Planning | Distributional Activities | Program Activities | Programs | Organization and Administration | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Contraceptive Methods | Population Characteristics | Demographic Factors | Population Document Number: 342776 |
| 27. Peer Reviewed Title: Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Author: Lue Y; Wang C; Cui Y; Wang X; Sha J; Zhou Z; Xu J; Wang C; Hikim AP; Swerdloff RS Source: Biology of Reproduction. 2009 Mar;80(3):484-92. Abstract: Prior studies have demonstrated that combined treatment of testosterone with a progestin induces a more rapid and greater suppression of spermatogenesis than testosterone treatment alone. We hypothesized that the suppressive effects of the combination of testosterone undecanoate (TU) injections plus oral levonorgestrel (LNG) on spermatogenesis may be mediated through a greater perturbation of testicular gene expression than TU alone. To test this hypothesis, we performed open testicular biopsy on 12 different adult healthy subjects: 1) four healthy men as controls; 2) four men 2 wk after TU treatment; and 3) four men 2 wk after TU + LNG administration. RNA isolated from biopsies was used for DNA microarray using the Affymetrix Human Genome U133 Plus 2.0 oligonucleotide microarrays. Gene expression with >or=2-fold changes (P < 0.05) compared with control was analyzed using the National Institutes of Health Database for Annotation, Visualization, and Integrated Discovery 2008 resource. The TU treatment altered the gene expression in 109 transcripts, whereas TU + LNG altered the gene expression in 207 transcripts compared with control. Both TU and TU + LNG administration suppressed gene expression of insulin-like 3; cytochrome P450, family 17, subfamily A1 in Leydig cells; and inhibin alpha in Sertoli cells; they increased proapoptotic transcripts BCL2-like 14, insulin-like growth factor-binding protein 3; and they decreased X-linked inhibitor of apoptosis protein. In comparison with TU treatment alone, TU + LNG treatment upregulated insulin-like 6 and relaxin 1, and downregulated RNA-binding protein transcripts. We conclude that TU + LNG administration induces more changes in testicular gene expression than TU alone. This exploratory study provided a novel and valuable database to study the mechanisms of action of hormonal regulation of spermatogenesis in men and identified testicular-specific molecules that may serve as potential targets for male contraceptive development. Language: English Keywords: UNITED STATES OF AMERICA | RESEARCH REPORT | MEN | MALE CONTRACEPTION | PROGESTERONE | SPERMATOGENESIS | TESTIS | TESTOSTERONE | CONTRACEPTION RESEARCH | LEVONORGESTREL | Developed Countries | North America | Americas | Demographic Factors | Population | Contraception | Family Planning | Progestational Hormones | Hormones | Endocrine System | Physiology | Biology | Reproduction | Genitalia, Male | Genitalia | Urogenital System | Androgens | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents Document Number: 341724 |
| 28. Peer Reviewed Title: Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model. Author: Meng CX; Andersson KL; Bentin-Ley U; Gemzell-Danielsson K; Lalitkumar PG Source: Fertility and Sterility. 2009 Jan;91(1):256-64. Abstract: OBJECTIVE: To investigate the effect of levonorgestrel and mifepristone on the expression of endometrial receptivity markers in a three-dimensional endometrial construct. DESIGN: In vitro study. SETTING: University hospital and research laboratory. PATIENT(S): Twelve fertile donors. INTERVENTION(S): Timed endometrial biopsy. MAIN OUTCOME MEASURE(S): Examine the effect of levonorgestrel along with another well-studied fertility-regulating drug, mifepristone, on the expression of endometrial receptivity factors in a three-dimensional stromal and epithelial cell coculture model by immunohistochemistry. RESULT(S): Both epithelial and stromal cells of in vitro endometrial construct showed the presence of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptors-(A+B), vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1 beta, and cyclooxygenase-2, whereas the expression of progesterone receptor-B (AR), integrin alpha(V)beta(3,) and MUC1 were confined to epithelialcells. Mifepristone up-regulated expression of epithelial estrogen receptor-beta and progesterone receptor-B and down-regulated stromal vascular endothelial growth factor and surface molecules MUC1 and integrin alpha(V)beta(3) as observed in vivo. Levonorgestrel had no effect on the expression of endometrial receptivity markers studied. CONCLUSION(S): This in vitro model expresses progesterone-regulated endometrial receptivity factors seen in the physiologic condition. Treatment with levonorgestrel did not affect the expression of these endometrial receptivity markers in contrast to mifepristone. This in vitro model holds the potential to study endometrial receptivity, the embryo-endometrial interaction, and develop new agents for fertility control. Language: English Keywords: SWEDEN | RESEARCH REPORT | IN VITRO | LABORATORY EXAMINATIONS AND DIAGNOSES | LEVONORGESTREL | RU-486 | DECIDUAL CELL REACTION | FERTILITY | Europe, Northern | Europe | Developed Countries | Clinical Research | Research Methodology | Examinations and Diagnoses | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Hormone Antagonists | Hormones | Endocrine System | Physiology | Biology | Cytologic Effects | Population Dynamics | Demographic Factors | Population Document Number: 329592 |
| 29. Title: Comparative performance of a combined injectable contraceptive (50 mg norethisterone enanthate plus 5mg estradiol valerate) and a combined oral contraceptive (0.15 mg levonorgestrel plus 0.03 mg ethinyl estradiol) in adolescents. Author: Molina RC; Sandoval JZ; Montero AV; Oyarzun PG; Molina TG; Gonzalez EA Source: Journal of Pediatric and Adolescent Gynecology. 2009 Feb;22(1):25-31. Abstract: STUDY OBJECTIVE: To compare in a regular non-clinical trial experience the efficacy, acceptability, and continuation rates of an injectable contraceptive containing 50 mg norethisterone enanthate plus 5mg estradiol valerate (IC) and an oral contraceptive containing 0.15 mg levonorgestrel plus 0.03 mg ethinyl estradiol (OC), among adolescent users. DESIGN: A total of 251 adolescents ages 14-19 were followed during 12 months. The IC group (124 subjects) was studied for 1044 cycles and the OC group (127 subjects) was studied for 1368 cycles. The users were not assigned in a random selection. Information was collected from clinical records. Groups were compared using Pearson chi-square, odds ratio (95% confidence interval), t-test, and proportion difference test. RESULTS: The IC group had significant differences in baseline social risk, confidence, psychiatric problems, consumption of alcohol, and number of sexual partners. At 12 months, the IC group showed significant decrease in weight and increase in hypermenorrhea. In the OC group, dysmenorrhea decreased, and hypomenorrhea and regular cycles were significantly more frequent. One pregnancy occurred in the OC group (Pearl Index: 0.88). Final continuation rates at 12 months were 41.9% and 37.8% for IC and OC, respectively. CONCLUSIONS: The monthly injectable is a recommended contraceptive option for adolescents, especially for those facing psychosocial risk factors. Language: English Keywords: CHILE | RESEARCH REPORT | CLINICAL RESEARCH | COMPARATIVE STUDIES | ADOLESCENTS, FEMALE | INJECTABLES | |