Weight gain, body image and sexual function in young patients treated with contraceptive vaginal ring. A prospective pilot study.

INTRODUCTION: Oral contraceptives could induce mood changes. As far as our knowledge, there are no studies in literature that have examined the role of vaginal contraception in self-perceived body image. AIM: To evaluate the effects of intravaginal contraception on weight gain and perceived body image in relation with the Beck's Depression Inventory questionnaire (BDI) and the McCoy Female Sexuality Questionnaire (MFSQ). METHODS: Twenty-one adult (18-35 years old) eumenorrheic (menstrual cycle of 25-35 days), lean (body mass index - BMI - of 19-25 kg/m2) women who were referred for hormonal contraception were administered the Stunkard Figure Rating Scale (FRS), BDI and MFSQ. Subjects were studied in basal condition and after 6 months of therapy with vaginal contraception (NuvaRing®; Organon-Schering-Plough Italia, Milan, Italy). MAIN OUTCOME MEASURES: BMI, FRS, MFSQ and BDI. RESULTS: After 6 months of therapy with NuvaRing®, both body weight (60.0 ± 8.3; p = 0.050) and BMI (22.1 ± 3.1; p = 0.028) slightly, but statistically, increased. FRS and BDI showed no differences after the vaginal contraception. Hormonal contraception was associated with a significant decrease in the two-factor Italian MFSQ score. CONCLUSIONS: Vaginal ring seems a good alternative to other hormonal contraceptive not significantly altering the female sexuality and not influencing the FRS and BDI.

Contraceptive Vaginal Rings: Do They Pose an Increased Risk of Venous Thromboembolism in Aesthetic Surgery?

UNLABELLED: Nuvaring (Organon, Kenilworth, NJ) is a vaginal contraception ring inserted by the patient. It was approved by the Food and Drug Administration in 2001 for the prevention of pregnancy. The intent of this paper is to increase the awareness of Nuvaring among plastic surgeons, and to explore the risks associated with its use. We report the cases of two cosmetic surgery patients. These patients developed deep venous thrombosis and pulmonary emboli in the postoperative period while using Nuvaring. The very advantages of the Nuvaring-the ease of use, the avoidance of daily administration, and the insertion and removal of the device by the patient-may lead to the failure of patients to recollect being on a vaginal ring for contraception. LEVEL OF EVIDENCE: 4 Risk.

The association between BMI and continuity of etonogestrel (ENG)-releasing implant.

OBJECTIVE: The etonogestrel-releasing implant is a long-acting reversible contraception that is recommended by the Food and Drug Administration for 3 years and has been proven to be highly effective and convenient. Adverse effects including irregular bleeding patterns, weight gain, and acne are reported to be the main reasons for treatment discontinuation. The aim of this study is to learn the association between body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) and the incidence of side effects and adherence to treatment. METHODS: This is a retrospective cohort study, conducted at a single university-affiliated medical clinic, including all women who underwent etonogestrel-releasing implant (Nexplanon®; New Jersey, USA, Organon USA Inc., Merck and Co) insertion between January 2019 and December 2021. Cases where abnormalities were reported during the insertion procedure or missing data were excluded from the study. Information on patients' demographic, medical history, obstetric and gynecological history, and follow-up was collected from electronic medical files. The primary outcome was defined as the rate of implant removal in the different obesity classes. Data are presented as median and interquartile range. The study was approved by institutional review board. RESULTS: The study population included 1318 women, of whom 466 (35%) requested early removal of the implant. Women's demographic and clinical characteristics were comparable between women who requested early removal and those with full-length treatment. The median time for early removal was 12 (6-20) months from insertion. Irregular bleeding was the most frequent reason for early removal in both groups and was more than twice as prevalent in the early removal group (239 [51.29%] vs 193 [22%], P = 0.001). The early removal group had fewer obese women (BMI ≥30) compared with women who had full-length treatment (163 [31.8%] vs 350 [68.2%], P = 0.03), with comparable rates of class 3 obesity women (BMI ≥40) (P = 0.68). Multi-regression logistic analysis including age, BMI, parity and side effects found that the presence of side effects is the only independent predictor significantly associated with early implant removal (B = 1.74, P = 0.04). CONCLUSIONS: Continuation of etonogestrel-releasing implant contraception treatment was associated with the presence of side effects that were more often reported in non-obese women. BMI was not found to be a significant factor influencing adherence to treatment.

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.

[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.

Comparative study on the efficacy and acceptability of two contraceptive pills administered by the vaginal route: an international multicenter clinical trial.

The efficacy and acceptability of two widely used oral contraceptive tablets, one containing 250 mg levonorgestrel and 50 micrograms ethinyl estradiol and the other containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, administered by the vaginal route were compared in 1055 women studied over 12,630 woman-months of vaginal contraceptive pill use. This multicenter clinical trial was performed in nine countries of the developing world by the "South to South Cooperation in Reproductive Health," an organization founded by scientists from the Third World working in the area of reproductive health, and the study was developed and coordinated by one of these centers. The findings of this study confirm the efficacy of both these tablets when administered by the vaginal route. Involuntary pregnancy rates at 1 year of 2.78 for subjects in the levonorgestrel group and 4.54 for subjects the desogestrel group showed no statistically significant difference between the two groups. However, total discontinuation rates of 47.01 for subjects in the levonorgestrel group and 56.33 for subjects in the desogestrel group showed a statistically significant difference between the two groups, and discontinuation rates attributable to prolonged bleeding of 0.6 for subjects in the levonorgestrel group and 3.2 for subjects in the desogestrel group were also significantly higher in the group of subjects using the desogestrel vaginal contraceptive pill. Blood pressure remained at admission values throughout treatment. A statistically significant weight increase from admission values occurred in both groups of subjects.

PIP: Efficacy and acceptability of 2 combined oral contraceptive pills administered vaginally are summarized. This is the 1st collaborative trial published by the South to South Cooperation in Reproductive Health. 1055 women participated in 12,630 cycles, in 9 countries, from June 1988 to May 1991. The pills were commercially available tablets containing 50 mcg ethinyl estradiol and 250 mg levonorgestrel (Schering AG, Sao Paulo, Brazil), or 30 mcg ethinyl estradiol and 15 mcg desogestrel (Organon, Sao Paulo, Brazil). Subjects were aged 17-39 younger and of lower parity from Mexico and Dominican Republic and older from Egypt and China. All had at least 1 pregnancy. 675 participated for 6 months, 470 for 1 year, 364 for 18 months, and 210 for 2 years. The 1-year discontinuation rate averaged 47.01% for the levonorgestrel group and 56.33% for the desogestrel group (p = 0.0061); 2-year discontinuation rates were 48.01% and 69.36, respectively, explained in part by higher involuntary pregnancy rates and prolonged bleeding rates in the desogestrel group. The most common medical reasons for stopping contraception were unplanned pregnancy, vaginal or vulval irritation, nausea, vaginal discharge and headache. Vaginal irritation was reported by 1%, 9 in each group. There were 32 pregnancies, 14 in the levonorgestrel and 18 in the desogestrel group. 17 were in missed pill cycles and the rest were method failures, 6 in the levonorgestrel group and 9 in the desogestrel group. The Pearl index varied from 0 in Nigeria to 12.24 in Mexico, and was 2.45 for levonorgestrel vs. 3.74 for desogestrel. There was a wide variation in discontinuation rates by center: Brazil and China had few, while many women from Dominican Republic, Mexico and Zambia left the study. Bleeding problems were common complaints, more so in the desogestrel group. There were 363 women with intermenstrual bleeding (only once in 80%), 148 with spotting (only twice in 65%). Bleeding duration was significantly less in pill cycles than baseline, pressure. Women gained an average of 1 kg over 2 years, more in the desogestrel group. The pregnancy rate of 2.78 is within the range reported for levonorgestrel rings.

Treatment of hirsutism with flutamide and a low-dosage oral contraceptive in polycystic ovarian disease patients.

OBJECTIVE: To evaluate the clinical and hormonal response of the antiandrogen flutamide (Eulexin, Schering Plough, Milan, SA, Italy) associated with a low dosage oral contraceptive (OC) in a group of hirsute women who were unresponsive to OC treatment. DESIGN: Twenty-two polycystic ovarian disease (PCOD) patients with hirsutism were treated with flutamide (250 mg twice/d) in association with ethinyl-E2 (0.030 mg/d) plus desogestrel (0.150 mg/d) (Practil 21; Organon, Rome, Italy) for 21 d/mo. SETTING: Patients were recruited in the Institute of Obstetrical and Gynaecological Pathology, St. Bambino Hospital, University of Catania, Italy. Hormonal assays were performed in the Hormone Laboratories of St. Bambino Hospital, University of Catania, Catania, Italy. MAIN OUTCOME MEASURE: Every 2 months the hirsutism score was evaluated using the Ferriman-Gallwey hair density index. Mean plasma concentrations of LH, FSH, E2, total T, dihydrotestosterone (DHT), androstenedione (A), sex hormone-binding globulin, DHEAS were determined. RESULTS: After 8 months treatment with flutamide and low dosage OC, the Ferriman-Gallwey score improved in all patients, mean values decreasing from 25.4 +/- 3.96 to 14.6 +/- 1.92. Plasma levels of total T and E2 were unchanged, whereas LH, FSH, A, and DHT values decreased significantly. Sex hormone-binding globulin levels showed a marked increase. CONCLUSION: Flutamide, associated with low dosage OC, favorably influence the hirsutism in PCOD women who are unresponsive to OC treatment alone.

Changes in androgens during treatment with four low-dose contraceptives.

The aim of the present study was to compare changes in the endogenous androgen environment in healthy women while on low-dose oral contraceptives (OCs). One-hundred healthy women were randomized to receive one of four OCs during six months: 21 tablets of Cilest, Femodeen, Marvelon, or Mercilon. During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded and the following parameters were measured: sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), testosterone (T), free testosterone (FT), 5 alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S) and 17 alpha-hydroxyprogesterone (170HP) while also the free androgen index (FAI) was calculated. Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month. There were no differences on body mass and blood pressure with the use of the four OCs. The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon (approximately 20% vs 45%). Mean serum SHBG and CBG increased significantly in all four groups approximately 250% and 100%, respectively. In each group CBG also increased significantly but less in women taking Mercilon (-75%) as compared to the others (-100%). Current low-dose OCs were found to have similar impact on the endogenous androgen metabolism with significant decreases of serum testosterone, DHT, A, and DHEA-S. They may be equally beneficial in women with androgen related syndromes such as acne and hirsutism.

PIP: Health researchers randomly assigned 100 healthy women aged 18-38 from the Netherlands and Saudi Arabia to one of four various oral contraceptive (OC) groups to undergo six cycles of OC therapy so they could evaluate changes in plasma concentrations of sex hormone binding globulin (SHBG), corticosteroid-binding globulin (CBG), albumin (Alb), testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A), dehydro-epiandrosterone-sulphate (DHEA-S), and 17 alpha-hydroxyprogesterone (17OHP). The four monophasic OCs were Cilest (35 mcg ethinyl estradiol [E2] and 250 mcg norgestimate), Femodeen (30 mcg E2 and 75 mcg gestodene), Marvelon (30 mcg E2 and 150 mcg desogestrel), and Mercilon (20 mcg E2 and 150 mcg desogestrel). There were 12 dropouts. Neither body weight nor blood pressure changed significantly during the study. All steroidal serum parameters (T, FT, DHT, A, DHEA-S, 17OHP, Alb) fell significantly during the six cycles of OC treatment (ratio of decrease, 1.3-3), regardless of OC type. These changes had appeared after cycle 4. The only significant difference between the OC groups was that the mean decrease of DHEA-S for Mercilon was lower than that for the other OC groups (21% vs. 43% for Cilest, 44% for Marvelon, and 34% for Femodeen; p 0.05). SHBG and CBG rose greatly during OC use in all four OC groups (mean increase = 263% and 94%, respectively; p 0.05). The increase in CBG was significantly less in the Mercilon group than in the other OC groups (74% vs. 96% for Cilest, 101% for Femodeen, and 102% for Marvelon; p 0.05). These findings show that OC use changed the endogenous androgen environment in the direction of hypoandrogenism. Thus, all four OCs can equally treat androgen-related syndromes (e.g., acne and hirsutism).

Release characteristics, ovarian activity and menstrual bleeding pattern with a single contraceptive implant releasing 3-ketodesogestrel.

The properties of a single contraceptive subdermal implant releasing 3-ketodesogestrel were assessed in fifteen women over twelve months. Serum levels of 3-ketodesogestrel were monitored regularly following insertion and after removal. The mean serum level of 3-ketodesogestrel was 245 pg/ml after 72 h (steady state) and 176 pg/ml after twelve months. All volunteers demonstrated ovulation inhibition throughout the study. Transient oestradiol peaks occurred during the study. No luteal activity was noted. The cervical mucus was rapidly rendered hostile to sperm migration. Two women withdrew from the study during the first six months for medical reasons. Both volunteers cited bleeding irregularity as the main cause, one complaining of oligomenorrhoea, the other of prolonged bleeding/spotting episodes. A small but significant increase in weight was noted during the study period.

PIP: 15 sterilized women participated in a clinical trial of the implant Implanon (Organon), a single ethylene vinyl acetate rod containing 60 mg 3-ketodesogestrel (3-KDG), the metabolite of desogestrel. The rod is 40 mm long, 2 mm in diameter and is packaged in its inserter. In this trial the implants were treated to simulate the 2nd year of use. The study subjects underwent intensive hormone and ultrasound monitoring for 72 hours after insertion, twice weekly for 6 weeks and at 6-month intervals. 13 women completed 6 months, 7 completed 12 months, and 5 continued the trial 24 months. There were no complications related to insertion or removal. 3-KDG levels rose to a steady state of 245 pg/ml by 72 hours, then fell to a mean of 17 pg/ml at 12 months. 90 pg/ml of 3-KDG is the critical serum level for anovulation. After removal, 3-KDG declined to 54 pg/ml in 3 days. Follicle development tended toward small follicles or those larger than 10 mm. There was no luteal activity, and LH, FSH and progesterone remained in the follicular phase range. Estradiol levels were not low enough to risk osteoporosis. There was no significant change in serum sex hormone binding globulin. Systolic blood pressure decreased significantly at 12 months; mean weight gain was 3.7 kg (range from loss of 4 kg to gain of 22 kg); a variety of bleeding irregularities were recorded by individual women.

[A clinical trial with the monophasic contraceptive Marvelon]. / Klinichen opit s monofazen kontratseptiv--Marvelon.

The authors present their clinical experience with a monophasic preparation consisting of 30 mcg ethynyl estradiol and 150 mcg desogestrel (Marvelon, Organon). 121 cycles of 24 fertile women were followed. The results show a full contraceptive success, a stable cycle control as well as a low incidence of the side effects.

PIP: The objective of the study was to assess the clinical effectiveness of the monophasic oral contraceptive Marvelon by examining its safety and its effectiveness in controlling the menstrual cycle as well as the frequency and types of side effects. 24 healthy women with an average age of 24.5 years (range of 18-33 years) were the subjects. 23 had previous reproductive events: 18 births, 5 spontaneous abortions, and 16 induced abortions. 17 women had used contraceptives sporadically: 3 postcoital pills, 8 triphasic pills, and 6 monophasic pills. During the year prior to initiating Marvelon use 2 women had experienced oligomenorrhea, 5 had had hypermenorrhea, 6 had had dysmenorrhea, and 3 had had irregular uterine bleeding. The observation period of contraceptive use lasted 4-6 months, during which a total of 121 cycles were evaluated without one single case of pregnancy. This meant a 100% contraceptive safety or a Pearl index of 0. 20 of the patients had stable cycles. 4 women with 13 of the 121 cycles (10.5%) had menstrual disorders. There were 5 cases of breakthrough bleeding and 8 cases of spotting. Weak dysmenorrhea occurred only in 2 patients. Other side effects included: nausea (2), headache (2), nervousness (2), mastodynia (3), vertigo (1), depression (1), and increase of body weight (2). As the duration of taking Marvelon increased the frequency of menstrual disorders declined. Not a single case of post-pill amenorrhea occurred. At the present time over 5 million women use Marvelon in the world. Epidemiological studies involving 14,903 women with a total of 98,225 menstrual cycles have revealed only 4 pregnancies or a Pearl index of 0.06. In the present study regular pseudomenstrual bleeding was confirmed in 89.5% of investigated cycles, which compares to 96.1% indicated in the literature. Marvelon proved to be a modern, safe contraceptive with stable control of the menstrual cycle, and which exhibited only minor side effects.

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.

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 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.

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.

Coeliac axis thrombosis associated with the combined oral contraceptive pill: a rare cause of an acute abdomen.

We report a case of coeliac axis thrombosis and splenic infarction presenting in a girl of 14 years who had been on the oral contraceptive pill (OCP), Marvelon (ethinyloestradiol 30 microg plus desogestrel 150 microg, Organon, Cambridge, UK), for 3 weeks. She had no other risk factors for thrombo-embolism. Diagnosis was made with duplex Doppler ultrasound and confirmed with dynamically-enhanced comput-ed tomography and magnetic resonance angiography, thus avoiding the need for percutaneous arteriography. Though mesenteric thrombo-embolic disease is recognised in association with use of the combined OCP, it has not previously been reported to affect the coeliac axis. Paediatricians and surgeons should be aware of the risks to young girls on the OCP, and consider it in their differential diagnosis of the acute abdomen.

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.

Comparative profiles of reliability, cycle control and side effects of two oral contraceptive formulations containing 150 micrograms desogestrel and either 30 micrograms or 20 micrograms ethinyl oestradiol.

OBJECTIVE: To compare two oral contraceptive pills, both containing 150 micrograms desogestrel, but with either 20 micrograms (Mercilon) or 30 micrograms (Marvelon/Desolett) ethinyl oestradiol (EE), regarding reliability, cycle control and side effect profile. DESIGN: A double blind, randomised, multicentre study over one year with follow up after three, six and 12 months. The women noted tablet intake and all bleedings on specifically designed diary cards. SETTING: University clinics, central hospitals and private gynaecological practices in Norway, Sweden and Denmark. SUBJECTS: One thousand women aged 18 to 40 years requesting oral contraceptive pills. MAIN OUTCOME MEASURES: Reliability, cycle control, side effects, blood pressure, body weight and haemoglobin. RESULTS: In a total of 4543 cycles with the 20 micrograms EE dose pill and 4688 cycles with the 30 micrograms EE dose pill, the number of pregnancies ascribed to method failure were 0 and 2, respectively. Irregular bleeding (break-through bleeding or spotting) was significantly more frequent with the 150/20 combination in about two-thirds of the cycles randomly distributed over the one year of the study. Mean blood pressure decreased slightly, particularly in the group on the 150/20 combination (about 1 mmHg), whereas mean body weight increased approximately 0.5 kg in the group with the 150/30 combination after 12 months. Haemoglobin did not change. Side effects other than bleeding problems were rare, but dizziness and mood changes were more frequent in the group on the 150/20 combination. Due to side effects, more women on the 150/20 combination discontinued the study during the one to three and four to six month periods, and women on this pill were also less positive about continuing the study drug at the end of the trial. CONCLUSIONS: Both pills have high contraceptive reliability and are well tolerated, but with the 150/20 combination the cycle control is less effective. However, in view of the potentially increased safety profile of the 150/20 combination, many women can be expected to accept some additional discomfort due to irregular bleeding.

PIP: A double-blind, randomized, multicenter study compared 2 combined oral contraceptives containing 150 mcg desogestrel and either 30 mcg (Marvelon/Desolett) or 20 mcg (Mercilon) of ethinyl estradiol, focusing on reliable pregnancy prevention and cycle control. The women were 300 Norwegians, 500 Swedes, and 200 Danes, 52% of whom switched from a prior brand of pill. Women completed bleeding diaries: all bleeding that did not start in the 7-day tablet-free interval and last for 7 or fewer days was considered irregular bleeding, either breakthrough bleeding or spotting. The 2 groups were similar except that those taking the 150/20 combination were slightly older. There were 2 pregnancies with the 20 mcg combination and 3 with the 30 mcg pill, 2 of which were considered method failures. In 8573 cycles analyzed there were more instances of irregular bleeding and amenorrhea with the 20 mcg pill than with the 30 mcg pill. Duration of breakthrough bleeding was not significantly different. Irregular bleeding was also more common n women switching from another brand of pill to a lower estrogen dose pill. Blood pressure decreased slightly on the 20 mcg ill and body weight rose slightly on the 30 mcg pill, but hemoglobin did not change. More women dropped out or chose not to continue taking the 150/20 mcg pill because of side effects, usually irregular bleeding, mood changes, dizziness, or weight gain. Despite these differences, there were enough women who tolerated the lower dose combination pill to merit continuing to take it.

[Ovarian activity, cycle behavior and tolerance of low dosage oral contraceptives: a comparative study]. / Ovarielle Aktivität, Zyklusverhalten und Verträglichkeit bei niedrigdosierten oralen Kontrazeptiva: Eine Vergleichsstudie.

In a double-blind randomized study, the suppression of ovarian activity, the effects on the cervix and endometrium, menstrual bleeding patterns and overall tolerance were assessed during administration of two low-dose oral contraceptives (20 micrograms ethinylestradiol EE, 500 micrograms norethisterone--Eve 20, Grünenthal, Aachen; 20 micrograms EE, 150 micrograms Desogestrel--Lovelle, Organon, Munich), 118 healthy women (ages: 18 to 35 years) with comparable bioprofiles (height, weight, menstrual cycle patterns) were studied in 10 investigation centres during medication with either Eve 20 (n = 59) or Lovelle (n = 59). During 3 treatment cycles, ovarian activity was evaluated by sonographic determination of follicular size and by simultaneous assessment of serum endocrine profiles (gonadotropins LH and FSH, ovarian steroids estradiol [E2] and progesterone [P]). Treatment cycles 4 to 6 served to evaluate the patterns of menstrual bleeding and the overall subjective tolerance on each contraceptive. While on the preparations, no ovarian activity (as judged by a lack of follicular growth and suppressed sex steroid levels) was found in over 90% of all investigated cycles. Follicular activity and/or cyst formation were detected in 18 of 173 cycles (Eve 20) and in 5 of 175 cycles (Lovelle) respectively. Gonadotropin levels were suppressed (LH < 6 IU/l, FSH < 8 IU/l) in most treatment cycles (Eve 20: 76.6% vs. Lovelle: 84.8%). Serum E2 concentrations exceeding 0.1 nmol/l indicated residual follicular activity in 19.3% (Eve 20) vs. 12.2% (Lovelle) of all cycles. As estimated by serum P levels over 5 nmol/l, ovulation had presumably occurred in 4.1% (Eve 20) vs. 2.9% (Lovelle) of treatments respectively. However, when the sonographic and endocrinological data were combined, no ovulation was documented in any treatment cycle. In addition, the quality of the cervical mucus was minimal and a low endometrial thickness was found in the majority of women, indicating strong progestogen effects of both contraceptives. Menstrual irregularities (intermenstrual spotting, break-through bleeding) occurred initially on each preparation, but were mostly resolved when the pills were continued. The acceptance of each investigated drug was rated as very good or good by most subjects. These observations allow us to conclude that the rate of ovarian suppression with inhibition of follicular activity is high under low-dose oral contraceptives. The different progestogens as components of these contraceptive pills display equally good anti-conceptive effects on both the cervix and the endometrium. Furthermore, the rate of irregular menstrual bleeding is acceptable for these low-dose contraceptives. The high acceptance of each preparation suggests that such agents will have a high rate of acceptability in clinical use.