[Norplant, new method of contraception in Portugal]. / Norplant, novo metodo da contracepcao em Portugal.

PIP: The Norplant contraceptive implant is a long-term, reversible method containing levonorgestrel (LNG) and became available in Portugal as of January 1996. It consists of six silastic capsules, which contain a 36 mg dose of LNG, and when inserted under the skin it provides a continuous release of LNG at the rate of 30 mcg. It is inserted during the first days of the menstrual cycle and provides protection against pregnancy for 5 years. It has been demonstrated that after removal 40-50% of the women become pregnant at the end of 3 months, about 80% at the end of 1 year, and 90% at the end of 2 years. It is particularly suited for women who are contraindicated to use estrogens or the IUD. Norplant can be used as soon as 6 weeks after delivery and while breast feeding. The associated pregnancy rate varies between 0.2 and 1.3 per 100 women-years. Its continuation rate is 60-90% at the end of 1 year and 50% at the end of 5 years. In users, alterations of the menstrual cycle, including amenorrhea, can occur; cycle normalization usually occurs within 9-12 months. A retrospective study was carried out concerning tubal ligations performed during 1993-94 at the Dr. Daniel de Matos Maternity Ward to confirm precise indications for sterilization and to study Norplant as a possible alternative. A total of 312 ligations were performed during this period. About 53% underwent sterilization because of medical contraindication to pregnancy, and the rest did not want any more pregnancies since they were 35 years old or older. The previous method of contraception used was, in order of frequency: coitus interruptus, hormonal methods, barrier and spermicidal methods, and IUDs. Only six patients had postoperative complications. Norplant as an effective long-term contraceptive is recommended in situations where a large degree of social, economic, and family instability exists.^ieng

Implantable contraception.

PIP: Research on contraceptive implants began when it was learned that steroids could be released from Silastic rubber capsules. The six-capsule Silastic drug delivery system, which would eventually be called Norplant, was by 1974 perfected and prepared for clinical trials. By 1978, data had accumulated to indicate a failure rate for Norplant after two years of only 0.6%, so Leiras Pharmaceuticals of Turku, Finland, was licensed in 1983 to manufacture Norplant, and Finland became the first country to give regulatory approval for distribution of the new contraceptive. The World Health Organization, after a 1984 evaluation, concluded that the Norplant system is an effective, reversible, long-term method of fertility regulation which is particularly appropriate for women in need of long-term contraceptive protection. Wyeth-Ayerst Laboratories began to distribute the device in the US after it met US Food and Drug Administration approval. 24 countries have now approved Norplant for distribution and use among women. This paper describes the Norplant contraceptive system, its mechanism of action, insertion and removal, effectiveness, contraindications, and adverse effects with regard to menstrual problems, medical problems, infection or pain, drug interactions, ectopic pregnancy, foreign body carcinogenesis, and other adverse reactions. It also notes use benefits in terms of contraceptive action, convenience, the reduction of adverse reactions for former oral contraception users, and the prevention of anemia, and lists categories of potential acceptors and women who may not wish to use Norplant.^ieng

Contraception in the diabetic woman.

Contraceptive prescription in women with current diabetes, type I or II, and in women with previous gestational diabetes must be highly effective and take into account the metabolic effects and risks particular to diabetes. This article concentrates on reversible, nonbarrier methods including oral contraceptives, long-acting progestins, and intrauterine devices with the goal of enabling the practitioner to develop individually tailored contraceptive therapy for these women.

PIP: Prescribing contraceptives to diabetic women requires cognizance of metabolic effects and the risks of type I or type II and gestational diabetes mellitus (GDM) in prediabetic women. Studies have show that poor maternal glycemic control in the 1st trimester in diabetic women has resulted in a twofold to threefold increased risk for congenital malformations. A reduction from 6.6% to 1.1% in malformations could be realized by euglycemic control before conception and during the first 8 weeks of gestation. A low-estrogen preparation should be selected and blood pressure should be monitored regularly. Progestins adversely affect carbohydrate and lipid metabolism, as they decrease glucose tolerance by increased insulin resistance, thus the selection of proper progestin dose/potency is important in prescribing OCs. The lowest-dose OCs may be prescribed under close medical supervision to women with insulin-dependent diabetes mellitus (IDDM) without serious vascular complications. Patients should be evaluated after the 1st cycle of OC use and every 3-4 months thereafter with monitoring of weight, blood pressure, postprandial glucose, and glycosylated hemoglobin levels. Women with prior GDM should be evaluated annually utilizing a 2-hour, 75-g glucose tolerance test (OGTT) at the postpartum visit. For OCs, a low-dose estrogen ( 0.05 mg ethinyl estradiol) and a low-dose/potency progestin (or = 0.50 mg of norethindrone or or= 0.100 mg of levonorgestrel) should be selected. The safety of prescription of OCs to women with type II diabetes is unclear, but a supervised program similar to that of IDDM patients is recommended. Currently neither of the long-term contraceptives, depo-medroxy-progesterone acetate (Depo-Provera) injection or the levonorgestrel-containing implant, Norplant, are recommended as first-time methods for women with diabetes. On the other hand, the IUD is an effective, reversible method, particularly for older women with hypertension, provided antibiotic prophylaxis is undertaken at the time of insertion.

Contraceptive choices for women with endocrine complications.

Previous confusion regarding the interference by oral contraceptives in measurements of endocrine function have been largely eliminated by the advent of improved, more sensitive assays. There are few if any contraindications to oral contraceptive use in patients with thyroid disease. Patients with prolactinoma can be treated with bromocriptine to restore fertility and prevent mineral loss. However, as a less expensive alternative, oral contraceptives can be prescribed to correct mineral loss, because there is no convincing evidence of an adverse effect on prolactinomas by the steroidal content of the pill. Oral contraceptives comprise a near ideal treatment modality for women with polycystic ovary disease because, among other effects, oral contraceptives reduce synthesis of androgen by inhibiting pituitary gonadotropin secretion.

PIP: The steroids in oral contraceptives (OCs) can change the synthesis of binding globulins for three major classes of hormones, thus physicians often cannot use the traditional measurements to evaluate endocrine disease. They should consider this when trying to expand their knowledge on contraception in women with endocrine conditions. Thyroid disease does not preclude OC use, but untreated thyroid disease may increase fetal morbidity and mortality. Women whose thyroid dysfunction is under control can use any contraceptive method. A does of 7.5 mg/day bromocriptine restores ovulation and normal plasma estrogen levels and reduces tumor size in women with prolactinoma (microadenomas are common and tend to be benign while macroadenomas are rare, but tend to be malignant) who do not want to become pregnant. OCs also restore ovulation and prevent bone mineral loss, but they do not reduce tumor size. Physicians do not agree on how to manage prolactinoma in pregnant women. Androgen excess is associated with polycystic ovarian syndrome (POC), the leading symptoms being hirsutism, acne, and abnormally infrequent menstruation. OCs are the most common and cost effective means to suppress gonadotropin secretion which, left unchecked increases ovarian androgen production. The most effective OCs are those with a progestin component which does not significantly affect androgenic activity. Newer progestins appear to have high specificity for the progestin receptor and reduced affinity for the androgenic receptor, thus someday they can perhaps effectively treat POCs. Gonadotropin-releasing hormone superagonists can induce the same effect as OCs, but tend to be cost prohibitive ($300-$500/month). Women with POCs are quite vulnerable to cardiovascular risk factors (e.g., hypertension and insulin resistance). Women with POCs should avoid use of IUDs and progestin-only implants.

Subdermal contraceptive implants in nurse-midwifery practice.

Subdermal contraceptive implants have only recently been approved for use in the United States. At present, only one subdermal contraceptive implant, Norplant, is approved in the United States. This article describes the development of Norplant, its efficacy and safety, a description of the system, education for clients, side effects, indications and contraindications, insertion and removal, incorporation into midwifery practice, and education for health professionals regarding its use.

PIP: The US Food and Drug Administration approved the contraceptive implant system, Norplant, in February 1990. It has been used in other countries for more than 15 years before the US approved it. The 6 subdermally placed capsules in the upper inner arm release 50-80 mcg levonorgestrel/day into the bloodstream, resulting in a 99.8% efficacy rate. Patient education and counseling, especially about changes in the bleeding pattern and Norplant's inability to protect against sexually transmitted diseases, are important to maintain client satisfaction and continued use of Norplant. Side effects, from most to least common, are changes in menstrual bleeding, constant bleeding, missed periods, weight gain/increased appetite, headache, oily skin or acne, weight loss/nausea, breast tenderness, nervousness or loss of appetite, and hair loss. It is rare when complications are so severe that they require removal of the implants. Contraindications to Norplant include active liver disease, active thromboembolic disease, breast cancer, pregnancy, and undiagnosed dysfunctional uterine bleeding. Antiepileptic medications, barbiturates, treatment for tuberculosis, and Butazolidin/phenylbutazone reduce Norplant's efficacy. A trained person should insert Norplant within the first 5-7 days of the menstrual cycle when it is evident there is no pregnancy. Some reports recommend that, after childbirth, it should be inserted 6 weeks postpartum to avoid hemorrhage. Yet, nurse-midwives at the Center for Addiction and Pregnancy at the Francis Scott Key Medical Center in Baltimore, Maryland, insert Norplant 24-48 hours postpartum in non-breast-feeding mothers with no increase in hemorrhage. Norplant must be removed no longer than 5 years after insertion. Certified nurse-midwives wanting to incorporate Norplant into their practices should follow the Guidelines for the Incorporation of New Procedures into Nurse-Midwifery Practice and have available a consulting physician who is familiar with and skilled in inserting Norplant. The manufacturer conducts training sessions for health professionals.

[Let's talk about Norplant: advances in steroidal contraception]. / Hablemos del Norplant: avances en anticoncepcion esteroidea.

PIP: Norplant, the subdermal levonorgestrel-releasing contraceptive implant, has undergone 28 years of study, clinical trials, and use by the general population. Its great advantage over combined oral contraceptives (OCs) is that it is free of estrogen and thus acceptable for use by many women with contraindications to estrogen. Norplant has few or no apparent effects on cholesterol, phospholipid, or triglyceride levels, and there is no evidence that Norplant use increases cardiovascular risk. Norplant releases a constant dose of levonorgestrel that varies from 350 ng initially to 290 ng after 5 years of use. The levonorgestrel is released directly into the circulation, avoiding the first hepatic passage. Norplant achieves its contraceptive effect by inhibiting the positive feedback exercised by estradiol on the hypothalamus and thus reducing levels of luteinizing hormone and follicle stimulating hormone, by rendering the cervical mucus inhospitable to passage of sperm, and by altering the composition of the endometrial tissue. It has been suggested that Norplant may affect tubal motility, but no studies in support of this hypothesis have been found. Secondary effects of Norplant use include decreased secretion of gonadotropins and consequently decreased frequency of ovulation, impaired luteal function, migraine or tension headaches, and occasionally such effects as facial chloasma or alterations in libido. The most frequent complications are dysfunctional uterine bleeding and irregular staining and spotting or amenorrhea. 70% of women experience such alterations of menstrual pattern with Norplant over 5 years of use. Norplant is contraindicated for diabetic women because of possible alterations in carbohydrate metabolism. Women who use certain antiepileptic or antitubercular drugs or barbiturates that affect the action of levonorgestrel should choose a nonhormonal contraceptive method. Acute or chronic cholestatic hepatic disease is an absolute contraindication. Although studies of the effects of Norplant on breastfeeding have not conclusively demonstrated any risks, the problem of steroid transfer to the infant through the breast milk has not yet been resolved. Several studies have confirmed the contraceptive efficacy of Norplant and calculated its failure rate at 2%, which makes it the second most effective method after sterilization. The rate of ectopic pregnancy is low. The implants should be inserted under aseptic conditions similar to those observed during any surgical procedure. Once the implants are removed, the serum concentrations of levonorgestrel decline rapidly. Most of the steroid is eliminated within days. Fecundity returns in the cycle following removal. 85% of women conceive within the 1st year after removal and 95% do so within 2 years.^ieng

Norplant.

PIP: The US Food and Drug Administration 1st approved the Norplant Contraceptive System in December 1990. Norplant clinical trials with 55,000 volunteers in 41 countries attest to its effectiveness as a safe and convenient longterm and reversible contraceptive. In 10-15 minutes, clinicians can insert the system's 6 silastic capsules containing levonorgestrel under the dermis of the inner side of the upper arm. Within 24 hours after insertion, Norplant can effectively protect from pregnancy. The capsules continuously release the levonorgestrel over 5 years to protect ovulation. Norplant can be used by almost all women including adolescents, postpartum women, and lactating mothers 6 weeks after delivery. It is especially suitable for women who want longterm birth spacing, to abstain from sterilization, who have encountered problems with other contraceptives, and who do not want to take estrogen. Women with active thrombophlebitis, thromboembolic disease, cardiovascular disease, undiagnosed abnormal vaginal bleeding, known or suspected pregnancy, acute liver disease, benign or malignant liver tumors, and breast cancer should not use Norplant, however. Its side effects include prolonged bleeding, spotting, and amenorrhea. High initial costs for Norplant in the US (range $500-1000) are preventing many women from adopting its use. In Tennessee, Medicaid and some private insurance companies cover Norplant insertion. Clinicians must provide adequate counseling, education, and patient advocacy in addition to proper skills for Norplant insertion and monitoring. Wyeth Laboratories has trained 25,000 physicians who have trained their medical colleagues and nurse practitioners. The nurse practitioner training programs at Emory University in Atlanta, Georgia includes Norplant insertion skills in its curriculum. The Tennessee Department of Health offers the public a network of trained Norplant providers. It also is working on developing Norplant guidelines including policy, procedures, medical management, counseling, and informed consent.^ieng

New concepts in contraception: Norplant subdermal implant.

PIP: 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.^ieng

International experience with NORPLANT and NORPLANT-2 contraceptives.

Experience encompassing more than 20,000 woman-years of use of NORPLANT capsules and 6,000 woman-years of trials of NORPLANT-2 rods is reviewed. Implant contraception repeatedly has been associated with low pregnancy rates and high continuation rates through five full years of use. Weight has proved to be a factor related to effectiveness. Women weighing less than 50 kg experienced cumulative five-year pregnancy rates well below 1 per 100, whereas the overall cumulative rate has been 3.5 per 100. Medical events reported during use that have led to discontinuation are analyzed from four large data sets.

PIP: Experience encompassing more than 20,000 woman-years of use of NORPLANT capsules and 6000 woman-years of trials of NORPLANT-2 rods is reviewed. Implant contraception repeatedly has been associated with low pregnancy rates and high continuation rates through 5 years of use. Weight has proved to be a factor related to effectiveness. Women weighing less than 50 kg experienced cumulative 5-year pregnancy rates well below 1 per 100, whereas the overall cumulative rate has been 3.5 per 100. Analysis is provided of medical events that have led to discontinuation, based on 4 large data sets.

Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment.

The contraceptive efficacy of progestin-only contraception was studied in epileptic patients using NORPLANT subdermal capsules. The effect of anticonvulsants on levonorgestrel plasma levels was determined. NORPLANT subdermal capsules were inserted into nine epileptic women, and ten control women using no medication. Venous blood samples were taken at 0, 1, 3, 6, 9 and 12 months after insertion and the concentration of levonorgestrel was determined by radioimmunoassay. At 3 to 12 months, the overall mean concentration of plasma levonorgestrel was significantly lower in the six epileptics taking phenytoin alone or in combination with other anticonvulsants (203 +/- 128 pg/ml, mean +/- SD) than in the controls (325 +/- 135 pg/ml, p less than 0.01). After one year, nine of the control patients continued the use of NORPLANT and no pregnancies occurred. Two of the nine epileptics became pregnant during contraception by NORPLANT. They both used phenytoin and their plasma concentrations of levonorgestrel were low near the time of conception. Levonorgestrel released from the capsules had no apparent harmful effects on epilepsy and none of the patients reported an increase in seizure frequency. The results show that contraception by the progestin levonorgestrel is not reliable in epileptic patients using anticonvulsants known to induce metabolizing enzymes of the liver.

Contraception by intradermal implants.

PIP: Steroid implants may offer a long lasting contraception with easy reversability. Of 360 women who completed 1 year trial using an implant containing 6 capsules of levonorgestrel, 3 pregnancies occurred with 2 in the 1st month. Another implant using 6 capsules of norgestrienone (R2010) was given to 338 women. 17 pregnancies were associated with this steroid. Neither implant was as effective as the Copper IUD but R2010 was significantly less effective. One-third of the women terminated use during the 1st year citing menstrual disturbances of irregular or prolonged bleeding plus amenorrhea as the main cause. Continuation rates were between 75% and 80% depending on geographic area. The remaining steroid in situ after 15 months showed R2010 ineffective for 2nd year use while enough norgestrel remained for several years protection. Another study followed 650 women using norgestrione implants for 6 months to 24 months and found more prolonged contraceptive effect. Mode of mechanism appeared to be inhibition of ovulation.^ieng