June 2001, Vol. 7, No. 2

Reproductive Health
Study Finds Norplant^® Safe and Effective

A five-year international postmarketing surveillance of users of the Norplant^® implant in eight developing countries confirms the safety and effectiveness of the method. The study compared the experiences of 8,000 Norplant users with those of 8,000 women who relied either on an intrauterine device (IUD) or sterilization. 

Researchers Olav Meirik, formerly of the World Health Organization (WHO), Timothy M. M. Farley of the WHO, and Irving Sivin of 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.

Five-year surveillance
The study followed Norplant users, women who had been sterilized, and users of copper-bearing or noncopper IUDs in Bangladesh, Chile, China, Colombia, Egypt, Indonesia, Sri Lanka, and Thailand. 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. Participants who used an IUD or were sterilized were matched by age to Norplant users. 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. 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 “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; resulted in continuing ill health; or led to death.

Reassuring data
The data “were reassuring with regard to serious health events,” says Meirik. The study revealed no significant excess of cancer or cardiovascular events, such as stroke, in Norplant users compared to women using nonhormonal methods. Furthermore, the number of such events was not greater than the expected number estimated from population-based incidence rates. No association was found between Norplant use and severe depression or severe connective tissue diseases, such as systemic lupus erythematosus. The rate of diagnosis of rheumatoid arthritis was low and not significantly different between Norplant users and women using an IUD or those sterilized. 

Twenty-two of 34 deaths during the study were the result of accidents, suicides, and homicides. The numbers and patterns of deaths were not significantly affected by the contraceptive method chosen.

The researchers found that the incidence of gallbladder disease was moderately higher in Norplant users (1.5 per 1,000 woman-years) compared with women in the control groups (1.1 per 1,000 woman-years), although such conditions occurred mainly in users in Chile and China. The incidence of hypertension was higher in current Norplant users (0.7 per 1,000 woman-years) compared with women in the control groups (0.4 per 1,000 woman-years). Borderline hypertension occurred at rates similar to those of hypertension. Because Norplant users had more frequent blood pressure measurements, the results might reflect a reporting bias, the researchers say. In addition, “the incidence of both gallbladder disease and hypertension was low in users of all the contraceptive methods studied,” says Sivin.

The cumulative five-year pregnancy rates were 1.5 per 100 women using Norplant, 0.7 per 100 women who were sterilized, 4.2 per 100 women using the copper IUD, and 13 per 100 women using the noncopper IUD. The great majority of the pregnancies occurred among women who had stopped using contraception.

Other reported health problems
The study confirmed a higher incidence of less serious disorders previously described in Norplant clinical trials and labeling, 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 attributable to the fact that the implant was a new method for both service providers and users, leading to a greater focus on health problems.

“This study, the largest and most comprehensive of its kind, shows Norplant to be an extremely safe and effective method of contraception,” says Sivin.

Source
Meirik, Olav, Timothy M.M. Farley, and Irving Sivin. 2001. “Safety and efficacy of levonorgestrel implant, intrauterine device, and sterilization,” Obstetrics & Gynecology 97(4): 539–547.

Outside funding
Family Health International, The Rockefeller Foundation, and World Health Organization

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