The combined vaginal contraceptive ring, nuvaring, and cerebral venous sinus thrombosis: a case report and review of the literature.

BACKGROUND: Combined oral contraceptives are known to confer a risk of venous thromboembolism, including cerebral venous sinus thrombosis (CVST), to otherwise healthy women. NuvaRing (Organon USA, Inc., Roseland, NJ) is a contraceptive vaginal ring that delivers 120 µg of etonogestrel and 15 µg of ethinyl estradiol per day. Its use has been associated with rare venous thromboembolic events, but few cases of CVST associated with NuvaRing have been reported. OBJECTIVE: To describe a case that illustrates the increased risk of CVST associated with use of NuvaRing. We describe the case of a NuvaRing user who presented to our emergency department with a headache, who was diagnosed with CVST. CONCLUSION: Evidence suggests that NuvaRing has at least as much prothrombotic potential as combined oral contraceptives. Thus, emergency physicians should suspect serious venous thromboembolic events, including CVST, deep venous thrombosis, and pulmonary embolism, in NuvaRing users in the proper clinical setting.

Indications for removal of etonogestrel implant within two years of use in Jos, Nigeria.

BACKGROUND: Implanon is a new long-term and reversible sub-dermal contraceptive implant in Nigeria. It is a single rod containing 68mg of etonogestrel meant to offer contraception for three years and marketed by Organon. OBJECTIVE: To determine the indications for removal of Implanon rods from clients within a two-year period. DESIGN: A retrospective review of 30 consecutive Implanon removals within the study period. SETTING: The fertility regulation unit of the department of obstetrics and gynaecology of the Jos University Teaching Hospital, North-Central Nigeria. RESULTS: A total of 30 clients requested for and had their Implanon rods removed out of 669 insertions constituting 95.5% crude continuation rate in the second year. The clients were of mean age 31.4 +/- 6.2 years, mean parity 2.9 +/- 1.8 and mean number of living children 2.7 +/- 1.6. There was an average weight gain of 1.9 kg. The most common indication for removal was menstrual disruption (33.3%). Desire for another pregnancy closely followed (30.0%). Weight gain was another indication for discontinuation (13.3%). Two women were pregnant at insertion of the implant. There was one failure of the method with pregnancy as a result. Spousal disapproval was an indication for removal in two cases. CONCLUSION: Like all progestin-only contraceptive methods, menstrual disruption was the most common indication for removal of implants. Inadvertent insertion of implants with existing pregnancy is of concern and should be avoided as much as is possible. In doubtful cases at insertion, this insertion should be deferred or serum beta-HCG should be assessed to exclude chemical pregnancy.

Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.

BACKGROUND: This study compared metabolic, hormonal and lipid profiles before and during use of a contraceptive vaginal ring (RING) releasing 15 mcg ethinyl estradiol (EE) and 120 mcg etonogestrel per day NuvaRing, Organon USA Inc., Roseland, NJ versus a low-dose oral contraceptive (PILL) containing 20 mcg EE and 100 mcg levonorgestrel daily (Aviane, Barr Pharmaceuticals Inc., Pomona, NY). STUDY DESIGN: Sixty-five women were randomized to either the RING or PILL treatment for five cycles. In the pretreatment cycle (Cycle Days 2-5) and during Weeks 2 and 3 of the fifth treatment cycle, a 75-g oral glucose tolerance test (OGTT) was performed. Baseline samples were used to evaluate basal hormonal, metabolic and lipid levels. RESULTS: Forty-two women completed the study. Basal insulin resistance (HOMA-IR) was slightly decreased, whereas a significant reduction in the insulin sensitivity index (IS(OGTT)) was found in women on PILL therapy compared to those in the RING group (p<.035). Pancreatic beta-cell function was not significantly altered with either treatment. CONCLUSION: The lower-dose, nonoral hormonal RING had a lesser impact on carbohydrate metabolism and greater reduction of free androgen and dehydroepiandrosterone sulfate levels than PILL treatment.

The contraceptive implant.

Contraceptive implants provide long-acting, highly effective reversible contraception. Currently, the only subdermal implant available to women in the United States is the single rod etonogestrel implant, Implanon (N.V. Organon, Oss, the Netherlands) approved by the Food and Drug Administration in July 2006. Implanon is currently approved for 3 years of use, provides excellent efficacy throughout its use, and is easy to insert and remove. Similar to other progestin-only contraceptives, Implanon can cause irregular vaginal bleeding. Implanon has been shown to be safe to use during lactation, may improve dysmenorrhea, and does not significantly affect bone mineral density, lipid profile, or liver enzymes.

Canadian Consensus Guideline on Continuous and Extended Hormonal Contraception, 2007.

OBJECTIVE: To serve as a guideline for health care providers on the use of continuous and extended combined hormonal contraception regimens, to prevent pregnancy, and to delay menses that affect health-related quality of life. OPTIONS: All combined hormonal contraceptive methods available in Canada that may be used in a continuous or extended regimen are reviewed, and the implications are discussed. OUTCOMES: Efficacy of cited regimens and assessment of their side effects, patient safety, medical usage and non-contraceptive benefits, cost-effectiveness, and availability in Canada. Indications for patient counselling are also provided. EVIDENCE: Medline, PubMed, and Cochrane Database were searched for articles published in English between 1977 and May 2007. Relevant publications and position papers from appropriate reproductive health and family planning organizations were also reviewed. VALUES: The quality of evidence is rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: The guideline is intended to help reduce unintended pregnancies and improve health-related quality of life in women who find their menses problematic. Increased awareness and empowerment of women, their partners, and health care professionals will improve their ability to make appropriate choices between continuous or extended and cyclic usage of these regimens. SPONSORS: The development of this guideline has been supported by unrestricted grants from Bayer HealthCare Pharmaceuticals, Janssen Ortho, Organon Canada Ltd., Paladin Labs Inc., Pfizer Canada Inc., and Wyeth Pharmaceuticals.

[Insertion problems, removal problems, and contraception failures with Implanon]. / Implanon: difficultés d'insertion et de retrait, échecs contraceptifs.

OBJECTIVE: Analysis of the results of a national pharmacovigilance study on Implanon, a contraceptive implant containing 68 mg of etonogestrel. PATIENTS AND METHODS: This survey concerns cases of pregnancies (contraception failures), of migrations and of insertion or removal problems with Implanon reported to French Regional Drug Pharmacovigilance Centres and to Organon SA between May 2001 and September 2002. RESULTS: In France, 39 unintended pregnancies were reported over 17 months. The pregnancies were in 77% of cases (N = 30) due to an insertion technique error (implant not found when pregnancy has been diagnosed). For 3 patients (7,6%), pregnancy was due to a failure of etonogestrel contraceptive effect, explained twice by its association with an enzymatic inductor drug. For 4 patients (10%), pregnancy was due to an untimely insertion (insertion after day 5 of menstrual cycle or woman already pregnant). For two patients, no information was available. The incidence of reported pregnancies in France is estimated at 0.359 / 10(3) implants [0.246-0.482], in accordance with a typical Pearl Index of 0.06 [0.04-0.08]. Twenty-eight suspected migrations (N = 11), problems or failures in removal of the implant (N = 11) and insertion difficulties (N = 6) were notified, corresponding to an incidence of 0.257/10(3) implants [0.162-0.363]. DISCUSSION AND CONCLUSION: Occurrence of pregnancy is possible with Implanon, due to errors in the insertion technique (device not really inserted) or to a non-respect of the SPC recommendations (drug-drug interaction or untimely insertion). Insertion problems can lead to localisation problems (implant not visible by X-ray) then needing further tests and even harmful practice (removal under general anaesthesia). That is why a real and strict training is highly recommended to physicians.

The return of the pharmaceutical industry to the market of contraception.

In the 1980s and 1990s, the litigious climate in the US had a catastrophic effect on sales of many major contraceptives. Although oral contraceptives escaped controversy, the intrauterine device (IUD) and Norplant(R) were two targets of damaging litigation. The IUD was withdrawn from the market in 1985. Since 1994 when the attacks began against Norplant, its US sales have dramatically declined, even though no fault has been found in the method or its development. In general, pharmaceutical companies were extremely hesitant to develop new contraceptives during this period. The bleak outlook, however, began to shift in the late 1990s, as fertility rates began to decrease worldwide and contraceptive users increased. By 2025, 2500 million women will comprise the customer base for contraception. Global pharmaceutical companies are now participating in expanding markets overseas and have launched and continue to develop a range of new long-term reversible, and highly effective, contraceptive products outside the traditional oral contraceptive field. Two new contraceptives on the way to the US market are: Mirena, a levonorgestrel-releasing intrauterine system manufactured by Schering-Leiras; and Implanon, a single implant system manufactured by Organon of the Netherlands. Other birth control methods soon to be launched include: emergency contraceptives, the contraceptive patch, monthly contraceptive injections, mifepristone for medical abortion, and modified oral contraceptives.

Etonogestrel implant (Implanon) for contraception.

Levonorgestrel 38 mg subdermal implant (Norplant), intended to provide contraception for 5 years, was withdrawn in the UK in 1999 due to unwanted effects (menstrual disturbances) and difficulties in removing the device. Since then, [symbol: see text]etonogestrel implant (Implanon-Organon), another progestogen--only subdermal contraceptive device, has become available in the UK. The manufacturer claims that etonogestrel implant provides contraception for up to 3 years and is easy to insert and remove. Here, we consider the place of etonogestrel implant.

Contraceptive implants.

Implantable contraception has been extensively used worldwide. Implants are one of the most effective and reversible methods of contraception available. These devices may be particularly appropriate for certain populations of women, including women who cannot use estrogen-containing contraception. Implants are safe for use by women with many chronic medical problems. The newest implant, Implanon (Organon International, Oss, The Netherlands), is the only device currently available in the United States and was approved in 2006. It is registered for 3 years of pregnancy prevention. Contraceptive implants have failure rates similar to tubal ligation, and yet they are readily reversible with a return to fertility within days of removal. Moreover, these contraceptive devices can be safely placed in the immediate postpartum period, ensuring good contraceptive coverage for women who may be at risk for an unintended pregnancy. Irregular bleeding is a common side effect for all progestin-only contraceptive implants. Preinsertion counseling should address possible side effects, and treatment may be offered to women who experience prolonged or frequent bleeding.

Effect of etonogestrel implant on serum lipids, liver function tests and hemoglobin levels.

BACKGROUND: This study aimed to assess the possible effects of etonogestrel implant (Implanon, Organon, Oss, The Netherlands) on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Hb levels in a sample of Turkish population. STUDY DESIGN: Healthy women of childbearing potential who had applied to our Family Planning Clinic for a contraceptive method and had chosen to have an Implanon insertion after thorough counseling about all family planning methods and screening for eligibility for Implanon use were enrolled in the study. Serum concentrations of TC, TG, HDL-C, LDL-C, AST, ALT and Hb levels were tested before and at 3 and 6 months after insertion. Baseline mean parameters were compared with mean parameters at 3 and 6 months for statistical significance using paired-samples t test. RESULTS: Eighty-two women eligible for the study were included. Mean age of the patients was 27.5+/-4.8 years. When compared to the baseline values, there was a statistically significant decrease in the TC (p<.001), HDL-C (p<.001) and TG (p=.006) at the end of the third month, while there was a significant increase in Hb values (p=.01). The decrease in TC (p=.001) and HDL-C (p<.001) and increase in Hb value (p=.03) persisted by the end of sixth month while the decrease in TG was transient. A statistically significant increase in mean ALT level was observed at 6 months (p=.03). CONCLUSION: The effect of Implanon on liver functions and lipid metabolism does not lead to unhealthy alterations. Increase in Hb can be attributed to the high frequency of amenorrhea in patients.

The contraceptive vaginal ring.

The contraceptive vaginal ring offers effective contraception that is self-administered, requires less frequent dosing than many other forms of contraception, and provides low doses of hormones. NuvaRing (Organon, Oss, The Netherlands), the only contraceptive vaginal ring approved for use in the United States, contains etonogestrel and ethinyl estradiol. It is inserted into the vagina for 3 weeks, followed by a 1-week ring-free period, and works by inhibiting ovulation. Most women note a beneficial effect on bleeding profiles and are satisfied with NuvaRing. Commonly reported adverse events include vaginitis, leukorrhea, headaches, and device-related events such as discomfort. Serious adverse events are rare. In Chile and Peru, progesterone-only vaginal contraceptive rings are available for nursing women. Studies are ongoing examining new formulations of vaginal contraceptive rings.

Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study.

BACKGROUND: This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women. STUDY DESIGN: On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION: Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.

The contraceptive efficacy of Implanon: a review of clinical trials and marketing experience.

OBJECTIVES: To evaluate the contraceptive efficacy of the etonogestrel-releasing implant Implanon as assessed in international studies and during nine years of marketing experience. METHODS: The analysis included 11 international studies and data collected during nine years of marketing experience (1998--2007). Seven of these studies were noncomparative; the four other studies included the 6-rod levonorgestrel implant system or an intrauterine device as a comparator. All studies except one were of at least two years in duration, and all had contraceptive efficacy as the objective. Market data were provided unsolicited to Organon, part of Schering Plough. RESULTS: The integrated efficacy analysis included 923 non-breastfeeding women who were exposed to the implant for 24,100 cycles. No in-treatment or pretreatment pregnancies were reported. Fifty posttreatment pregnancies were reported, six of which occurred within 14 days of implant removal, indicating that fertility had quickly returned. Over a nine-year marketing period an overall pregnancy rate of 0.049 per 100 implants sold (estimated Pearl Index = 0.031 based on all pregnancies reported) was calculated. When only counting contraceptive method failures the pregnancy rate amounts to 0.010 per 100 implants sold (estimated Pearl Index = 0.006). CONCLUSION: Implanon is a highly effective and quickly reversible subdermal method of long-acting hormonal contraception for women. Typical use of this implant achieves a contraceptive protection exceeding 99%.

The effects of Implanon on menstrual bleeding patterns.

OBJECTIVES: To evaluate an integrated analysis of bleeding patterns associated with use of the subdermal contraceptive implant Implanon (etonogestrel, Organon, part of Schering-Plough) and to provide physician guidance to optimize patient counselling. METHODS: Data from 11 clinical trials were reviewed (N = 923). Assessments included bleeding-spotting records, dysmenorrhoea, and patient-perceived reasons for discontinuation. Bleeding patterns were analysed via reference period (RP) analyses. RESULTS: Implanon use was associated with the following bleeding irregularities: amenorrhoea (22.2%) and infrequent (33.6%), frequent (6.7%), and/or prolonged bleeding (17.7%). In 75% of RPs, bleeding-spotting days were fewer than or comparable to those observed during the natural cycle, but they occurred at unpredictable intervals. The bleeding pattern experienced during the initial phase predicted future patterns for the majority of women. The group of women with favourable bleeding patterns during the first three months tended to continue with this pattern throughout the first two years of use, whereas the group with unfavourable initial patterns had at least a 50% chance that the pattern would improve. Only 11.3% of patients discontinued owing to bleeding irregularities, mainly because of prolonged flow and frequent irregular bleeding. Most women (77%) who had baseline dysmenorrhoea experienced complete resolution of symptoms. CONCLUSION: Implanon use is associated with an unpredictable bleeding pattern, which includes amenorrhoea and infrequent, frequent, and/or prolonged bleeding. The bleeding pattern experienced during the first three months is broadly predictive of future bleeding patterns for many women. Effective preinsertion counselling on the possible changes in bleeding patterns may improve continuation rates.

Acceptability and side-effects of Implanon in Switzerland: a retrospective study by the Implanon Swiss Study Group.

DESIGN: A multicenter, retrospective study of the single-rod contraceptive implant, Implanon (NV Organon, Oss, The Netherlands), was carried out in Switzerland in 1183 women. METHODS: Assessments included duration of use, bleeding pattern, side-effects and subjective acceptability and satisfaction with the method. RESULTS: A total of 991 women (84%) had at least one follow-up visit and 306 (26%) had two visits with a mean duration between insertion and follow-up of 224 days (7.4 months) and 347 days (11.4 months), respectively. Implanon was removed prematurely in 235 women (24%), primarily because of side-effects (20%) and for family planning reasons (4%). Side-effects leading to discontinuation were mainly bleeding disturbances (45%), acne (12%) and other reasons (15%). The mean duration between insertion and removal for discontinuers was 280 days (9.2 months). Side-effects related to bleeding (visit 1) included infrequent bleeding (28%), amenorrhea (33%), prolonged bleeding (15%), and metromenorrhagia (frequent and heavy bleeding) (16%). Other reported side-effects at visit 1 included dizziness (12%), acne (11%), mood swings (8%) and headache (5%). The incidence of side-effects reported at visit 2 was generally comparable to that at visit 1. CONCLUSIONS: The results of this study show that early discontinuation of implant use is primarily due to bleeding problems. Extensive counseling before implant insertion may help to prevent this. It is also important to develop an easy solution to successfully treating progestogen-induced bleeding disturbances.

Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol.

OBJECTIVE: The purpose of this study was to compare cycle control and tolerability of the NuvaRing (NV Organon, Oss, The Netherlands), a novel combined contraceptive vaginal ring, with a standard combined oral contraceptive pill. STUDY DESIGN: Healthy women aged 18 to 40 years who requested contraception received either NuvaRing or a combined oral contraceptive containing 30 microg ethinyl estradiol and 150 microg levonorgestrel for 6 cycles in 3 similarly designed studies. Each cycle comprised 3 weeks of ring or pill use, followed by 1 ring- or pill-free week. RESULTS: Two hundred forty-seven women began the studies, 121 women with NuvaRing and 126 women with the combined oral contraceptive. Withdrawal bleeding occurred in virtually all cycles in both groups. In the NuvaRing groups, the incidence of irregular bleeding was < or =5% in all cycles; this was lower than the combined oral contraceptive groups (5.4%-38.8%). Furthermore, the incidence of a normal intended bleeding pattern was significantly higher in the NuvaRing groups than in the combined oral contraceptive groups (P <.01). Both contraceptives were well tolerated. CONCLUSION: NuvaRing has excellent cycle control and is well tolerated.