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The Norplant System of levonorgestrel implants and the Depo Provera contraceptive Injection of sterile medroxy progesterone acetate suspension (DMPA) are longterm, progestagen-based contraceptive delivery systems designed to overcome noncompliance which are under review for use in Canada. 150 mg of DMPA, a pregnane compound derived from progesterone, is injected every 3 months. Peak plasma concentrations are reached in 24 hours and plateau for 3-4 months before gradually declining. After termination, ovulation returns on average in 4.5 months, and conception occurs at a median time of 10 months. 90% conceive by 24 months. In the Norplant system, a steady daily supply of 50-80 mcg of levonorgestrel, a gonane progestin derived from the testosterone nucleus which has both progestogenic and androgenic receptor affinity, diffuses from 5 Silastic implants, which must be replaced every 5 years. Ovulation and fertility return rapidly after rod removal. The actual and lowest expected failure rates are equal for both systems. The failure rate for DMPA is .3 pregnancies per 100 women years, while that for levonorgestrel is .4% in 1 year. Although neither method affects blood pressure, DMPA appears to affect carbohydrate metabolism by impairing glucose tolerance and increasing insulin production. Lipid metabolism is also affected. 5% of those who use levonorgestrel discontinue it because of side effects, including headache, mastodynia, and acne; 19.1% of DMPA users did so, especially for weight gain and menstrual cycle abnormalities. Both methods have a higher frequency of menstrual abnormalities than normal. 27.7% of levonorgestrel users experienced prolonged bleeding, while 17% experienced spotting during the first 6 months. However, normal menses usually returned within a year, and only 7.9% discontinued use because of cycle abnormalities. In 1 study, less than 10% of DMPA users experienced normal cycles, and in another study 35% experienced amenorrhea (500/700 discontinued use). Amenorrhea replaced irregular bleeding with continued use, occurring in 68% of users by 2 years. There is also some concern about DMPA and breast cancer and bone loss. Based on 1 case-control study of 110 women with breast cancer who had taken DMPA, the relative risk is highest for those between ages 25 and 34 who use DMPA longer than 6 years. A WHO study concluded that the relative risk of developing breast cancer, because of DMPA, is inversely related to duration of use. A Phase IV study on DMPA and bone mineral density has been undertaken.
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PMID:A comparison of levonorgestrel implants with depo-medroxyprogesterone acetate injections for contraception. 1231 30

This study presents findings on the socio-demographic and health characteristics, continuation rates, menstrual disturbances, and changes in menstrual patterns as well as other side effects among a sample of 952 1st time acceptors of the injectable contraceptive Depo-Provera during 1978-1980 in Colombo, Sri Lanka. Those continuing to use the method were observed for 24 months. The reasons for discontinuation are discussed based on another study that focused on 321 discontinuers who received Depo-Provera from the same clinic. The overall continuation rates at 12 and 24 months were 58% and 29%, respectively. Relatively older and higher parity women had lower continuation rates than younger and lower parity women. The occurrence of amenorrhea rose sharply foloowing the 1st dose and stabilized such that about 1/3 of those continuing with Depo-Provera became amenorrheic. 1/4 of the women experienced menstrual disturbances such as spotting and irregular bleeding. Other side effects, including vomiting, headache, and dizziness, affected 6% of the women following the 1st dose, but declined gradually over time. Over the course of the observation, 41-66% of the women appeared to gain weight. The 2 primary reasons for discontinuing Depo-Provera were non-medical: 1) the desire to have another child and 2) the decision to be sterilized. The findings suggest that Depo-Provera has played a signinficant role in Sri Lanka in 2 ways: 1) its use has provided desired pregnancy spacing for those who wished to have another child and 2) it has assisted couples by providing them with time (without the fear of pregnancy) to decide to stop having children and then get sterilized.
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PMID:Depo-Provera use in Sri Lanka: acceptor characteristics, continuation and side effects. 1234 Nov 88

Depot medroxyprogesterone acetate (DMPA, Depo-Provera) is used for contraception by 8-9 million women in more than 90 countries, including the US, as of January 1993. Pharmacologically active levels of DMPA persist for 3-4 months following injection. A 150 mg dose is used most often for high contraceptive efficacy every 3 months. Norethindrone enanthate (NET-EN, Noristerat) is somewhat less widely used and is not marketed in the US. Injectables act primarily by inhibiting ovulation, lowering the levels of follicle-stimulating hormone and luteinizing hormone. Approximately 50% of women using DMPA for 1 year report amenorrhea whose occurrence is less frequent with NET-EN. Menstrual changes are the most frequent causes of discontinuation of injectables. In cases of heavy bleeding it is appropriate to undergo gynecological examination to rule out unrelated conditions, such as vaginitis, cervicitis, or cervical lesions. The use of conjugated estrogen (12.5-2.5 mg daily) for 10-21 days will minimize bleeding. Some women using injectables experience headache, dizziness, bloating of the abdomen or breast, and mood changes. Long-term use of DMPA or NET-EN can often result in 1-3 kg weight gain. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives was launched in 1979 to examine cancer risks with the use of DMPA in Thailand, Mexico, and Kenya. The relative risk of breast cancer was 1.21, which was statistically not significant. In women diagnosed with breast cancer under age 35, short-term exposure to DMPA was associated with a slightly increased breast cancer risk, which, however, was not associated with duration of use. DMPA dramatically lowers the risk of endometrial cancer for at least eight years following discontinuation of its use. DMPA did not alter the risk of cervical cancer. Fertility returns in 70% of former users within 12 months; it is suitable for postpartum and lactating women, and provides other noncontraceptive benefits.
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PMID:Injectable contraception: the USA perspective. 1234 20

"New Era for Injectables," a report published in the most recent issue of the Johns Hopkins University School of Hygiene and Public Health's Population Reports, notes that injectable contraceptives are among the most effective family planning methods. Most clinical trials report less than one pregnancy per 100 women during the first year of use, making injectables as effective as Norplant implants, the best copper IUDs, and voluntary sterilization. Injectables also protect women against ectopic pregnancy, help to prevent endometrial and possibly ovarian cancer, and may help women with anemia and sickle-cell disease. The major side effect of injectable use is changes in menstrual bleeding. Some women also experience weight gain, and a few report headaches, dizziness, abdominal discomfort, acne, and moodiness. The most widely-used injectable is the progestin-only DMPA (depot medroxyprogesterone acetate), known under the brand name Depo-Provera and manufactured by the Upjohn Company. Women receive an injection every 3 months. Another progestin-only injectable, NET EN (norethindrone enanthate), is taken every 2 months. Cyclofem and Mesigyna, two new monthly injectables which combine estrogen and progestin, are currently being introduced in a number of countries. Worldwide, 1.5% of all married women of reproductive age who use some form of family planning use injectables. The highest level of use among such women is in Indonesia and Thailand where 15% and 12%, respectively, use injectables. Donor agencies have been responding to increasing numbers of orders for injectables from family planning programs in developing countries, while the UN Population Fund, the largest supplier, shipped 12 million doses of injectables in 1992 and 20 million in 1994. The 1992 US Food and Drug Administration approval of DMPA has made it possible for the US Agency of International Development to respond to requests for it.
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PMID:Millions of couples to have choice of injectable contraceptive. 1234 10


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