Compared to the risks inherent in pregnancy and daily activities of living, the increased risk of nonfatal venous thromboembolism (VTE) among users of oral contraceptives (OCs) containing desogestrel and gestodene is relatively benign. About 20-30 cases of nonfatal VTE per 100,000 users of third-generation OCs containing these progestins can be expected compared to 10-15 cases per 100,000 users of levonorgestrel-containing OCs. Pregnancy, on the other hand, confers an increased risk of about 60 cases of nonfatal VTE per 100,000 women. Since OCs remain the most popular reversible method of birth control, their discontinuation because of VTE concerns would have serious public health consequences in terms of unwanted pregnancy prevention. Moreover, OCs confer a number of noncontraceptive health benefits, including protection against ovarian and endometrial cancer, osteoporosis, benign breast disease, ovarian cysts, and pelvic inflammatory disease. The lives saved by OCs should be considered in any analysis of the small VTE risk they may impart.

A review of recent epidemiologic studies that have detected an association between the use of oral contraceptives (OCs) containing the progestins gestodene and desogestrel and venous thromboembolism (VTE) risk suggests evidence of bias. Reviewed are five major case-control and cohort studies: World Health Organization Collaborative Study, Boston Collaborative Drug Surveillance Program Study, European Transnational Study, and the Leiden Study. Three major sources of bias could account for the increased VTE risk among users of third-generation compared to second-generation OCs: 1) selective prescription of newer formulations to higher-risk women; 2) the increased tendency for women with suspected VTE to be more likely to be referred for diagnostic testing and hospitalization if they are taking the newer OCs rather than older formulations; and 3) attrition of susceptibles. The lack of any proposed biological basis for the observed association between VTE and the new progestins, compared with previous knowledge about the responsibility of estrogen for increased VTE risk, raises additional doubts about the findings. Any evaluation should balance the effects of OCs on overall risk of cardiovascular disease against protection from pregnancy and noncontraceptive health benefits such as a reduced risk of certain cancers.

Recent studies suggesting that oral contraceptives (OCs) containing the progestins desogestrel and gestodene are associated with a two-fold increased risk of nonfatal venous thromboembolism (VTE) compared to earlier formulations have raised new issues for clinicians. The increased risk of 20-30 cases of VTE per 100,000 women annually compares with 60 VTE cases associated with pregnancy. Women with a documented history of unexplained VTE should not use OCs, and when there is a family history, physicians should weigh factors such as age of onset of thrombosis in the affected relative, the clinical setting (e.g., after surgery or trauma), and severity of the episode. The effects of OCs on procoagulants and anticoagulants are minor, except in the 5% of women with factor V Leiden mutation. A clotting assay can determine activated protein C resistance and a polymerase chain reaction test can identify the presence of this mutation; however, widespread screening of OC users is not recommended due to the low incidence of factor V Leiden and the low likelihood these women will develop clots. The present state of knowledge about OCs and VTE risk supports the application of informed clinical judgment.

Irregular menstrual bleeding, the most common side effect of Depo-Provera use, is being managed by some physicians through administration of estrogen and/or ibuprofen. A practitioner from the Jones Institute for Reproductive Medicine in Norfolk, Virginia, reported that women with 8-10 days of bleeding over 2 weeks are administered 0.02 mg of ethinyl estradiol for 10 days; bleeding generally stops in 5 days. Other physicians prescribe an estrogen patch. If estrogen is contraindicated, patients are given 800 mg of ibuprofen 3 times a day for 5 days. In all cases of heavy bleeding apparently related to Depo-Provera use, other causes (e.g., cervical malignancy, uterine fibroids, sexually transmitted diseases) should be ruled out before treatment is initiated. Finally, several clinicians noted that counseling Depo-Provera acceptors to anticipate irregular bleeding for as long as a year is perhaps the most effective management strategy.

Advantage 24 is a new contraceptive gel that makes use of bioadhesive technology to offer 24 hours of protection relying on the spermicide nonoxynol-9 (N-9) in lower concentrations. If a proposed US Food and Drug Administration (FDA) rule is enforced N-9 may be examined closely. The manufacturer, Whitehall-Robins Healthcare in New Jersey, stopped production of the Today contraceptive sponge because of the costs of complying with FDA standards. The Advantage 24 gel costs twice as much as the sponge. It is made in Switzerland and distributed by an Illinois company. Any vaginal contraceptive containing N-9 would be approved by the FDA as long as it complied with guidelines laid down in an FDA monograph. However, the registration of the gel could not be confirmed. The product uses a bioadhesive technology concept that natural substances adhere to epithelial and mucosal tissues in the body. Polycarbofil is mixed with water, N-9, and mineral oil to create an emulsion that allows for a time-release mechanism, but at any given time only 2 mg of N-9 is available to kill sperm. The final formula for Advantage 24 is 52.5 mg per dose. Too much N-9 can be toxic, as demonstrated by the Today sponge, which contained 1000 mg of N-9. In Kenya prostitutes using it frequently experienced 3 times as many genital lesions as those using a placebo. A study of Advantage 24 by a Miami laboratory involved 250 women, 22-45 years old, who had had prior tubal ligations. When the gel was applied 15-30 minutes before intercourse the efficacy rate was 98%; it was 91% for those applying it 12 hours before; and it was 86% when the gel was applied 24 hours ahead of time. FDA compliance officers are intrigued about the claim that the gel lasts 24 hours. However, if the claim is held up by research data, women will have an easily available, portable, efficient, aesthetic, and highly effective contraceptive.

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.

Participants at the 1995 meeting of the Society for Adolescent Medicine learned that weight gain during Depo-Provera use may be associated with dissatisfaction and discontinuation among adolescents and that adolescents who were on a diet were more likely than those who were not to be engaged in risky sexual behavior (51% vs. 37.5%, respectively, were sexually active) and to worry about sexually transmitted diseases and pregnancy (24.3% vs. 14.4% and 47.5% vs. 24.9%, respectively). In the first study, researchers learned that giving early second injections of Depo-Provera to adolescents did not affect their bleeding patterns and increased the body mass index (BMI) two-fold (e.g., BMI at 3 months, 0.4 vs. 0.99). Teens who used oral contraceptives (OCs) before Depo-Provera were more likely to be satisfied with Depo-Provera than those who did not use OCs (87% vs. 52% on regular injection cycle and 39% receiving early second injections). A possible explanation for weight gain among adolescent Depo-Provera users is that the hormone directly stimulates the brain\'s hunger centers, thus increasing appetite. The hormone also interferes with serotonin, which influences satiety and stabilizes moods. Another risky behavior among dieters in the second study was alcohol use before sex (23.9% for dieters vs. 14.3% for non-dieters). Heavy dieters were more likely to have been date-raped than both moderate dieters and non-dieters (20.3% vs. 13.8% and 9.2%, respectively). These findings suggest the need for clinicians to screen adolescents for eating disorders before prescribing a contraceptive method. They should discuss dieting, body image, and age at menarche and identify risk factors. Girls who achieve puberty before their peers tend to engage in risky sexual behaviors and to have more depressive episodes during high school.

The Norplant implant system consists of 6 silastic capsules which deliver levonorgestrel to protect against pregnancy over 5 years. Clinical trials were conducted in 46 countries. The 5-year cumulative pregnancy rate is 3.9%. Norplant\'s efficacy falls as weight increases. Its failure rate is lower than that of combined oral contraceptives and most IUDs. Counseling is linked to acceptability. Medical personnel should be trained in counseling potential Norplant acceptors. They must undergo formal training in insertion and removal of Norplant. The first year and fifth year continuation rates are 75-90% and 25-78%, respectively. Bleeding irregularities are the main reason for discontinuation and the most commonly reported side effects. Levonorgestrel changes the cervical mucus and suppresses ovulation and the endometrium. Toxicological and teratological data on levonorgestrel and silastic show that Norplant is safe. It appears that Norplant does not cause any major pathological changes in the endometrium, liver, kidney, and adrenal and thyroid glands. Levonorgestrel in Norplant is linked to a slight increase in serum glucose levels which are not of significant consequence. Its effects on lipids and lipoproteins are not clear. Fertility returns to Norplant users shortly after removal. The return to fertility pattern basically matches that of other methods. Contraindications of Norplant use are confirmed or suspected pregnancy, previous ectopic pregnancy, breast cancer, cancer of the genital tract, cerebrovascular or coronary artery disease, acute liver disease, and undiagnosed abnormal genital bleeding. Norplant should be inserted subdermally in the upper arm during the first 7 days after menstruation begins. The capsules must be removed after 5 years if pregnancy is to be avoided. Before family planning programs provide Norplant, managers should make sure the staff is adequately prepared. Health personnel, counselors, potential users, and the public need informational materials on Norplant.

The risk of breast cancer is increased by an early menarche, late age at 1st birth, and by a late menopause which implicates ovarian steroids in the initiation or promotion of breast cancer, as some breast cancers are estrogen dependent. A study from the Centers for Disease Control found no association between breast carcinoma and duration of combined oral contraceptive (COC) use. A recent analysis of 27 reports published between 1980 and 1990 suggests that the risk of breast cancer may be slightly increased in younger, nulliparous women who have used the older, higher dose COCs for more than 8 years. The ever-decreasing doses of estrogen and progestogen cause confusion regarding COCs and the risk of breast cancer. Of 15 major publications, 8 have identified no increased risk of cervical neoplasia and 7 have found significant increased risk. The Oxford Family Planning Association Study showed that both cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma occurred more frequently in the oral contraceptive group related to the duration of use. The Royal College of General Practitioners\' Study showed that women taking the COC for more than 10 years had an increased risk of cervical cancer. With the effects of sexual activity controlled, COC users had no increased risk of invasive cervical cancer, however, they had an increased risk of CIN. A reduction in risk of endometrial cancer (an estrogen-dependent tumor) by 20%, 40%, and 60% after COC pill use containing potent progestogens for 1, 2, and 4 or more years has been reported. Several studies confirm the protective effect of COCs against the risk of ovarian cancer. Hepatocellular carcinomas seem to occur more frequently in COC users than in nonusers. Depot medroxyprogesterone acetate has been implicated in causing breast tumors, but it was successful in the treatment of endometrial carcinoma. There is some evidence that the risk of CIN may be increased with COC use, but the risk of breast cancer is still no clear.

Until recently, Africa\'s fertility rates showed no sign of change in spite of the vast resources committed to decreasing population growth. Now there are early indications of success in parts of Nigeria, Botswana, Zimbabwe, and Kenya. In Kenya, between 1984 and 1989, total fertility fell from 7.7 to 6.7, the crude birth rate fell from 52/1000 to 46/1000, and the contraceptive prevalence rate rose from 17% to 27%. Public awareness of modern contraceptive techniques is above 70% in much of Africa, and in Kenya it is up to 90%. Injectable contraceptives are very popular. In October 1992, they were finally licensed by the United States Food and Drug Administration. Injectable contraceptives were first used in Africa in the late 1960s. They were withdrawn from the Bangladesh family planning program, and they were banned in Zimbabwe in 1981. 2 injectable contraceptives administered by deep intra-muscular injection are widely available. Depo medroxyprogesterone acetate (DMPA) or Depo-Provera is normally given in a dose of 150 mg every 12 weeks. Norethindrone enanthate (NETEN) is given in a dose of 200 mg every 8 weeks. DMPA has been used by more than 10 million women. It is repeatedly endorsed by the WHO and the IPPF and has the lowest failure rate of any method of reversible contraception. Side effects include spotting or amenorrhoea, and rarely, menorrhagia. Injectables are suitable for women who are breast feeding, as they may even increase the quantity of breast milk. Norplant, an implanted device developed by the Population Council, releases progestogen at a low, steady rate for 5 years. There is less progestogen in a 5-year Norplant than in the 3-month dose of DMPA. The implant can be removed at any time and fertility is quickly restored. Norplant is becoming increasingly available throughout Africa.