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The US Food and Drug Administration (FDA) has not approved any injectable contraceptives, but, in December 1990, it approved Norplant, an implantable contraceptive. Family planning providers insert 6 capsules, each with 36 mg levonorgestrel, in a fan shape under the dermis of the upper arm. Norplant protects against pregnancy for at least 5 years . Fecundity returns within 2 weeks after capsules' removal. The steady low levels of levonorgestrel keep down both luteinizing hormone and follicle stimulating hormone levels. It suppresses ovulation and thickens the cervical mucus. Contraindications of Norplant are active thromboembolism, undiagnosed genital bleeding, acute liver disease, liver tumors, and breast cancer. Phenytoin and other drugs which speed up liver metabolism reduce Norplant's efficacy. The leading side effect of Norplant is irregular bleeding patterns. Some less common side effects include headaches, nervousness, dizziness, and acne. First year continuation rates range from 76 to 99% and 25 to 78% for 5 years of use. More than 85% of Norplant users are satisfied. Both continuation and satisfaction are associated with patient counseling. Research and development of biodegradable and other nonbiodegradable implants is ongoing. The most common injectable contraceptive in the world is Depo-Provera. 150 mg of Depo-Provera every 3 months suppresses ovulation, deteriorates the endometrium, thickens cervical mucus, and reduces motility of the tubes, thereby providing adequate protection against pregnancy. Some research shows Depo-Provera use significantly increases the low-density lipoprotein to high-density lipoprotein ratio, thereby increasing the risk for atherogenesis. Effectiveness rates match those of Norplant. Norethindrone enanthate was the first injectable contraceptive. Even though 40 countries approve it, the US does not. Animal studies of injectable microspheres or microcapsules with either progestogen or progestogen and estrogen are in progress.
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PMID:Injectable and implantable contraceptives. 138 11

User compliance is not a problem for the recently approved subdermal, longterm contraceptive delivery system, Norplant. It delivers 50-80 mcg of levonorgestrel/day during the 1st year and 30-35 mcg for years 2-5. The levonorgestrel is encased in 6 36 mm x 2.4 mm capsules which are placed in the upper arm in 5-10 minutes using local anesthesia. Since the implants systemically release levonorgestrel, the shock to the liver experienced in oral contraceptive (OC) users does not occur. Levonorgestrel prevents pregnancy by decreasing luteinizing hormone and follicle stimulating hormone which prevents ovulation, reducing the rate of ovum transfer in the tube, making the endometrium incompatible for implantation, and making the cervical mucus too thick and scanty for sperms to migrate if ovulation does occur. 1-year pregnancy rates for Norplant users are much lower than for women who use other contraceptives (0.6/100 users vs. 2.3/100 for OC users and 2.4/100 for IUD users). The ectopic pregnancy rate is also low (1.47/1000 Norplant users). The 1-year continuation rate is 80% compared with 50% for OC users. Fertility returns within 3 months for 50% of users and within 1 year for 80%. Because Norplant does not adversely affect lipid metabolism there is no increase in the risk of atherogenesis. Menstrual irregularities are the leading side effect of Norplant. The irregular cycles tend to occur during the 1st 3-6 months after insertion. Other side effects include headaches, acne, breast discharge, weight gain, and transient ovarian cysts. Contraindications are abnormal uterine bleeding, possible pregnancy, active liver disease, and women taking phenytoin. The cost for the initial exam and insertion of the Norplant capsules is $500 at Planned parenthood of the Rocky Mountains in Colorado (mean=$8.30/month vs. $13/month for 5 years of taking OCs). Due to the possibility of exploitation of women and involuntary infertility, nurse practitioners must thoroughly explain the system to each patient and answer all questions so the patient can give informed consent.
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PMID:New concepts in contraception: Norplant subdermal implant. 156 6

The Norplant implant is described: the release rates and serum levels of levonorgestrel, the mode of action, the indications and contraindications, the effectiveness, incidence of ectopic pregnancy related to Norplant use, metabolic effects, advantages and disadvantages, insertion, the role of counseling, and management of side effects (menstrual bleeding changes, headache, weight changes, mastalgia, and acne), continuation rates and reasons for termination, and removal. Norplant is currently the most effective method of contraception. Counseling is important in order to provide women with as much information for informed consent and to increase awareness and interest in Norplant. In a clinical trial in California, 95% expressed a high level of satisfaction upon implant removal and 71% desired Norplant again; 91% recommended Norplant to friends. 82% reported the side effect of menstrual change; 66% reported 2 or more side effects. Clinical development is ongoing for other sustained release contraceptives. Norplant was developed by the International Committee for Contraceptive Research of the Population Council, and manufactured by Huhtamaki Oy/Leiras Pharmaceuticals in Turku, Finland. Clinical trials have been conducted since 1975. 20 nations have approved its use, and more than 1.5 million women use it. Silastic rubber tubing encapsulates 6 capsules of 36 mg/capsule crystalline levonorgestrel, a strong progestin. Implantation is done just under the skin in a fan shape; levonorgestrel is released at 80 mcg/day for 6 months, and 30-35 mcg/day for the remainder of use. The mode of action is not completely understood, but the assumption is that it is similar to the progestin-only pills. The mechanisms that alter fertility are 1) the change in hypothalamic-pituitary level to inhibit midcycle luteinizing hormone surge, while follicle stimulating hormone and estradiol levels remain within the normal range, 2) the thickening of the cervical mucus which prevents the entry of sperm into the upper genital tract, and 3) the suppression of the estrogen-induced cyclical maturation of the endometrium. It is not an abortifacient. Contraindications are few, but include active thrombophlebitis, undiagnosed abnormal genital bleeding, known or suspected pregnancy, benign or malignant liver tumors, and known or suspected breast cancer of progestin-dependent neoplasms.
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PMID:Innovations in contraception: the Norplant system. 159 35

The Norplant System consists of 6 capsules each containing 36 mg of crystal line levonorgestrel (LNG), for a total dose of 216 mg LNG. The capsules are inserted subdermally in the mid-upper arm, and LNG diffuses continuously through the capsule walls for 5 years. In the United States the Norplant System was approved in December 1990. The initial rate of hormone delivery is about 85 mcg/day, then decreases over the next 9 months to 5 mcg/day, and over the ensuing 9 months to 35 mcg/day. Thereafter, the diffusion rate levels off for the next 3.5 years, averaging around 30-35 mcg/day. Removal results in a drop in the plasma concentration of levonorgestrel to below contraceptive levels within 24 hours and below the detectable limit of .1 pg/ml at 96 hours. Preliminarily data from 402 users over 5 years show improvements of Norplant produced better efficacy in all weight classes and a lowered cumulative rate of 1.1 pregnancies of 100 users. The pregnancy rate for the first year of use is 02., better than for oral contraceptives. Side effects include headache, nervousness, nausea, dizziness, dermatitis, acne, change of appetite, breast tenderness, minimal weight gain, some change in hair distribution, and adnexal enlargement. Adverse reactions include breast discharge, possible cervicitis, musculoskeletal pain, abdominal discomfort, leukorrhea, and vaginitis. More than the usual number of bleeding days occurred in slightly more than one fourth of the patients, prolonged bleeding in 27.6% spotting in 17.1% and amenorrhea in 9.4% of patients. Hyperlipidemic users should be observed for possible low-density lipoprotein elevations. The cumulative discontinuation rate for pregnancy was 3.9 per 100 users; for bleeding irregularities the rate was 25.1 per 100 users, and for other medical results it was about 22.4 per 100 users. Personal reasons for discontinuation accounted for 38.7 per 100 users, equivalent to a cumulative continuation rate of about 30 per 100 users over the 5-year duration.
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PMID:The NORPLANT system of contraception. 168 4

This literature review compares the merits and disadvantages of the levonorgestrel-releasing IUD made by Leiras Pharmaceuticals, Turkey, Finland (LNG-IUD-20), with the Nova-T, Copper-T (TCu) and 220C, and Copper-T-38-Ag (TCu-380Ag). This IUD releases 20 mcg levonorgestrel daily from a Silastic sleeve on the vertical shaft containing 52 mg. The plasma level stabilized after a month at about 0.2 ng/ml, about half as high as that seen with Norplant implants. It is identical in size to the Nova-T. The Cu-T IUDs differ with respect to copper wire or sleeves, or silver-cored wire. The chief studies reviewed here were 2 multi-center trails primarily in European countries, and a 2 large multi-center trials in India. Cumulative pregnancy rates were 0.0 to 0.6 per 100 users for the LNG IUD, compared to slightly higher failures for inert or copper IUDs. While removal rates for bleeding, pain and pelvic inflammatory disease were lower for the LNG-IUD-20, removals for oligomenorrhea, amenorrhea and hormonal side effects were higher than for the other IUDS. In the Indian trials, removals for amenorrhea and irregular bleeding were much higher than rates reported in the European studies, resulting in significantly lower continuation rates overall. The results pointed to district benefits for the LNG-IUD-20, such as lower blood loss and anemia, relief of dysmenorrhea and menorrhagia, as well as possible lower risks of ectopic pregnancy in case of failure, less PID (pelvic inflammatory disease), and the claim by the maker that strictly correct placement is not necessary. Disadvantages of the LNG-IUD-20 are more difficult insertion due to the wider diameter; oligomenorrhea, amenorrhea and irregular bleeding; hormonal side effects such as acne, weight gain, nausea, headache and breast tension; and potential risk of functional ovarian cysts. The LNG-IUD-20 is considered comparable to copper IUDs in effectiveness, safety, longevity, and return to fertility after removal. Users should be counseled that the oligomenorrhea or amenorrhea is neither a medical problem or indicative of infertility, is common for the 1st 2 months, is reversible on removal, may signal an improved hemoglobin profile, relief of dysmenorrhea, and may be preferred to heavy bleeding from other IUDS. The program implications of this IUD are potential lower incidence of ectopic pregnancy and PID. The effect of its use on breast feeding, cost-effectiveness compared to Norplant, in-country manufacture, and cultural acceptance need to be determined in specific locales.
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PMID:An evaluation of the levonorgestrel-releasing IUD: its advantages and disadvantages when compared to the copper-releasing IUDs. 177 15

Sustained released progestin-containing subdermal implants, the first new contraceptives to be released in 30 years, have the advantages of being easy to use, completely reversible, highly effective, and free of some of the health risks associated with combined oral contraceptives. The Norplant implant system, consisting of 6 levonorgestrel-filled silastic capsules, is being used by more than 500,000 women around the world and was approved for use in the US in late-1990. Because Norplant does not contain estrogen, it can be used safely by women with elevated blood pressure or a history of thromboembolic disease. Clinical trials have revealed first-year continuation rates of 76-90% compared with 50% for the pill. The most common reasons for requesting removal of Norplant are menstrual irregularity (prolonged menstrual bleeding, spotting between periods, or amenorrhea), headache, and weight gain. Plasma levonorgestrel concentrations are below contraceptive levels within 48 hours of removal, and most women resume normal ovulatory cycles during the first month after method discontinuation. Studies of carbohydrate metabolism, liver function, blood coagulation, immunoglobulin levels, serum cortisol levels, and blood chemistries have failed to reveal significant alterations in Norplant acceptors. Although some studies have recorded reductions in cholesterol, and triglyceride levels, lipoprotein levels return to pretreatment values by the end of the first year of use. Biodegradable implants that eliminate the need for surgical removal and implants that provide contraceptive protection for only 1-2 years could further increase the affordability and acceptability of this method. Under development are the Capronor and norethindrone/cholesterol pellet systems, both of which are shorter term and biodegradable.
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PMID:Subdermal progestin implant contraception. 190 16

Many recent advances in fertility control have involved progestin-only contraception. The progestin-only oral contraceptive, which has a failure rate of 1-2.5%, is especially suited to women who are breastfeeding or cannot tolerate estrogen. The levonorgestrel implant, Norplant, is effective for 5 years and has a 1.5% failure rate. Currently under development is Norplant-2--a system that requires 2 rather than 6 capsules, lasts for 3 years, and is as effective as Norplant-1. Also under development is a biodegradable progestin-only implant. However, there are many side effects associated with these methods. Irregular bleeding occurs in 60-70% of Norplant acceptors and leads 12-20% of these women to discontinue implant use. Headaches and acne occur in 5-20% of users of levonorgestrel methods. More significant are concerns that progestin tends to increase low density lipoprotein levels. Although initial human trials have indicated a drop of 5-15% in both these levels, studies in macaque monkeys have found that progestin-only contraception is more likely to cause atherosclerosis than an estrogen-progestin formulation.
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PMID:Progestin-only contraception. 202 98

An 18-year old patient bearing a subcutaneous Norplant implant in the left upper arm for 2 years visited a gynecological clinic. The implant rods were removed under local anesthesia because of the increasing pigmentation of the skin, and she switched to oral contraceptive use. Norplant contains a total of 216 mg of levonorgestrel (LNG) in 6 silastic rods, each 3.4 cm long. Norplant-2 consists of 3 rods with a length of 4.4 cm providing a total of 140 mg of LNG. It has been in use since 1974 in Chile, and subsequently in Brazil, Indonesia, Thailand, Africa, and to a lesser extent in Scandinavia. It works via the continuous release of 30-50 mcg doses of progesterone daily that induces cervical mucous changes whereby sperm penetration is thwarted; nidation does not occur, and ovulation is also often inhibited. The Pearl-Index reaches .1-1.1 in the first 5 years of use. The most important side effects are menstruation changes (oligo- and amenorrhea), weight gain, and headache. The continuation rate is similar to that of the IUD: 95% through the 1st year of use, and 75% through 3 years reported from Chile and China. Reversibility is a major advantage: 50% of women become pregnant within 3 months after removal, 86% within 1 year, and 93% within 2 years. In the Netherlands sits acceptance is clearly distinct from prevalence in Chile and China, and it has only a minor role in applicability when other contraceptives fail.
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PMID:[Norplant in The Netherlands]. 210 35

Oral contraceptives (OCs, long-acting progestins (LAPs), and IUDS are reviewed in terms of new information on safety and efficacy. OC formulations are described and their mechanism of action and efficacy indicated. Reports are provided for thromboembolism, hemorrhagic and thrombotic stroke, ischemic heart diseases, alterations in lipid and hypoprotein and carbohydrate metabolism, hypertension, coagulation changes, breast and cervical cancers, and such minor side effects as menstrual irregularities, nausea, headaches, weight gain, premenstrual syndrome effects, and mood and libido changes. Noncontraceptive health benefits and clinical considerations are discussed. Norplant, as the only long acting progestin available in the US is described in terms of its formulations, mechanism of action, sequelae and metabolic effects, menstrual irregularities, metabolic effects, nuisance side effects, candidates for insertion, method of insertion and removal, and continuation rates. 2 IUD types are identified as the only ones available in the US, Progestasert T and T-Cu-380A (Paragard). Mechanism of action, efficacy, candidates, major sequelae such as salpingitis, infertility, and uterine perforation, minor sequelae such as metrorrhagia and dysmenorrhea, and other considerations are indicated. OCs in the US contain an average of 35 mg of ethinyl estradiol and assorted progestins e.g.s, ethynodiol diacetate, norethindrone acetate, nortestosterone derivatives with a complex mechanism of action. The failure rate for use effectiveness is 6 pregnancies/100 woman years. Modern formulations have combined rates of no more than 50 to 100 adverse events/100,000 users. Some of the effects are indicated as follows: Thromboembolism accounts for 60% of adverse effects and appears to be declining along with hemorrhagic and thrombotic stroke, however, modern use studies are only partially available. Myocardial infarction related to OC use may be embolic, and has a low risk at 7/100,000 users. Low-dose contraceptives substantially reduce the associated risks. Those with risk factors need close monitoring. Norplant is useful for those not wanting to take a daily regimen and is commonly accompanied by menstrual irregularity and sometimes headaches. Continuation is 80% after the 1st year and 40% after 5 years. Candidates for IUDs are parous women in monogamous relationships, who are not at risk for salpingitis, which is related to IUD use, or sexually transmitted diseases. Continuation is 70% after 1 year compared with 50% of OC users.
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PMID:Modern trends in contraception. 212 11

Norplant offers long-term contraception through the use of subdermal capsules filled with levonorgestrel. The 6 capsules are implanted in the inside part of the upper arm. The levonorgestrel is released from the capsules gradually, providing contraception for about 5 years. The primary mechanism of action of Norplant is suppression of ovulation. Studies have shown a pregnancy rate of 0.6/100 women years after 1 year and a cumulative rate of 1.5/100 woman-years at 5 years. Principal side effects are irregular menstrual bleeding and headaches. No changes in carbohydrate metabolism, blood coagulation, or liver function have been reported. Lipid levels have decreased 5% to 15%. After removal of Norplant, fertility returns rapidly, and there have been no adverse effects on infants. Norplant is currently approved in 12 countries; clinical trials are being conducted in 37 countries.
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PMID:Norplant: subdermal implant system for long-term contraception. 249 46


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