Study finds Norplant as safe and effective as IUDs and sterilization

Study finds levonorgestrel contraceptive implant is as safe and effective as IUDs and sterilization

GENEVA AND NEW YORK - A five-year international postmarketing surveillance of users of the Norplant� implant in eight developing countries "confirms the safety with respect to serious disease and the high contraceptive efficacy" of the method, according to a study in the April 2001 issue of Obstetrics & Gynecology. The study compared some 8,000 Norplant users with about 8,000 women who relied either on an intrauterine device (IUD) or sterilization to determine the safety of these methods in developing-country settings and assess the risk of rare adverse events that may not have been identified earlier in clinical trials.

Researchers from the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) and the Population Council conclude that Norplant is "not associated with any material risk of major morbidity compared with the two control groups." This study is the first prospective postregistration surveillance of a newly introduced contraceptive in developing countries. The principal authors are Olav Meirik, formerly at the World Health Organization (WHO), Timothy M. M. Farley, WHO, and Irving Sivin, Population Council. Complete details of the methods and results of the study will be published shortly in the journal Contraception.

Dr. Paul Van Look, Director of the Department of Reproductive Health and Research at WHO, said, "The study demonstrates that all three methods are very safe and provide excellent long-term protection against unplanned pregnancy and considerably reduce the risk of ectopic pregnancy." The postmarketing surveillance, he said, also showed the feasibility of conducting large multicenter cohort studies in developing countries.

Five-year surveillance

Involving investigators at 32 family planning clinics in eight developing countries (Bangladesh, Chile, China, Colombia, Egypt, Indonesia, Sri Lanka, and Thailand), the study followed 7,977 Norplant users, 6,625 users of copper-bearing or non-copper IUDs, and 1,419 women who had been sterilized. Women were enrolled from 1987 to 1991 and were followed for five years, even if they discontinued use of the method, switched to another method, or became pregnant. The women made regular visits to the study clinics every six months, reported any health problems, and kept diaries of contacts with other health providers and facilities. The follow-up was completed in 1997, with over 78,323 woman-years of observation. Ninety-five percent of the women enrolled remained in the study and were accounted for at the end of the five-year follow-up period. The annual method continuation rates for both Norplant and IUD users averaged more than 90 per 100 women.

All complaints, symptoms, and diseases were recorded and classified either as a "major health event" or an "other health problem." Major health events were potentially life-threatening problems that required hospitalization, convalescence of at least one month, or medication for three months or more, left sequelae, or led to death.

Data reassuring for serious health events

Dr. Olav Meirik, who directed the study at WHO, said that the data "were reassuring with regard to serious health events." The report showed no significant excess of malignant neoplastic disease or cardiovascular events, such as stroke or venous thromboembolism in Norplant users compared to women using nonhormonal methods. Furthermore, the number of such events was not greater than the expected estimate from population-based incidence rates. There was little or no association between Norplant use and diabetes or thrombocytopenia. No association was found between Norplant use and severe depression or severe connective tissue diseases, such as systemic lupus erythematosus. The rates of diagnosis of rheumatoid arthritis and polyarthropathies were low and not statistically significantly different between Norplant users and women using an IUD or those sterilized.

Twenty-two of 34 deaths during the study were due to accidents, suicides, and homicides. There were no differences in the number or patterns of deaths according to the contraceptive method chosen.

The other major health events reported in the study mostly related to diseases of the digestive and genitourinary systems, reflecting expected patterns of disease among otherwise healthy women of reproductive age in developing countries. The researchers found that the incidence of gallbladder disease was moderately higher in Norplant users compared with women in the control groups, though this occurred mainly in users in Chile and China. While the overall incidence of hypertension was low in all contraceptive groups, the combined incidence of hypertension and borderline hypertension was higher in current Norplant users compared with women in the control groups. Because Norplant users had more frequent blood pressure measurements, the results might partially reflect a reporting bias, the researchers said. The risks of acute pelvic infection, low abdominal pain, and dysmenorrhea were lower in Norplant users than in women using IUDs or those sterilized.

Pregnancies

The majority of the pregnancies (914) occurred among women who had stopped using contraception. An additional 310 women using IUDs became pregnant; most of these pregnancies were in China and most were in women using non-copper IUDs, which have a higher failure rate than copper-bearing IUDs. Annual pregnancy rates during the period of use of Norplant, the copper IUD, and sterilization use were less than one per 100 women.

Other reported health problems

The study confirmed a higher incidence of less serious disorders previously described in Norplant clinical trials and labelling, such as irregular or excessive menstrual bleeding, amenorrhea, and ovarian cystic enlargement not requiring hospitalization. A variety of symptoms and conditions, ranging from headaches and mood changes to respiratory tract and skin problems, were also more frequently reported by women using Norplant than by IUD users and sterilized women. However, the higher incidence of these complaints by Norplant users may have been partly due to the fact that the implant was a new method for both service providers and users, leading to a greater focus on health problems.

"Safety and Efficacy of Levonorgestrel Implants, Intrauterine Devices, and Sterilization," Olav Meirik, M.D., Ph.D., Timothy M.M. Farley, Ph.D., and Irving Sivin, M.A. for the International Collaborative Post-marketing Surveillance of Norplant�. Obstetrics & Gynecology, Vol. 97, No. 4, April 2001.

The UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction was established by the World Health Organization in 1972. It coordinates, promotes, conducts and evaluates international research in reproductive health. As the main instrument within the United Nations system for research in this field, the Programme brings together health care providers, policy-makers, scientists, clinicians and consumer and community representatives to identify and address priorities for research aimed at improving reproductive health, especially in developing countries.

The Population Council is an international, nonprofit, nongovernmental organization that seeks to improve the well-being and reproductive health of current and future generations around the world and to help achieve a humane, equitable, and sustainable balance between people and resources. The Council conducts biomedical, social science, and public health research and helps build research capacities in developing countries. Established in 1952, the Council is governed by an international board of trustees. Its New York headquarters supports a global network of regional and country offices.

The study was conducted by WHO, Population Council, and Family Health International, Research Triangle Park, NC, USA, with additional support from the Rockefeller Foundation, New York, NY, USA.

For further information from WHO, journalists can contact Mr. Jitendra Khanna, Department of Reproductive Health and Research, WHO, Geneva. Telephone (+41 22) 791 3345. Fax (+41 22) 791 4171. Email: [email protected].

For further information from the Population Council, journalists can contact Ms. Sandra Waldman, telephone 212/339-0525; Email: [email protected] or Ms. Christina Horzepa, telephone 212/339-0520; Email: [email protected].