CHAPTER 1.1 LITERATURE REVIEW AND OBJECTIVES
1.1.5 DISCONTINUATION PATTERNS
1.1.5.2 Side Effects Leading to Discontinuation ofDMPA and NET-EN As described earlier in this chapter, bleeding disturbances are the most commonly
reported side effect for discontinuation ofIPCs. Although there is little published data for South Africa users, bleeding disturbances, mainly amenorrhoea, are the most common as reported in a study on IPC use undertaken in a family planning clinic in Soweto
(Beksinskaet al, 2001a). In one study,undertaken in New Zealand, weight gain was given as the most common side effect leading to discontinuation,followed by heavy bleeding (Colli et al, 1999).
Bleeding Disturbances
Some studies report that DMPA users were more likely to discontinue use of the method due to amenorrhoea than NET-EN users. For instance, a statistically significant difference was found between DMPA and NET-EN given every 12 weeks,for the 12-month gross cumulative discontinuation rate for amenorrhoea (1.8 per 100 woman-years for NET-EN
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and 11.5for DMPA) (World Health Organization, 1977). The later World Health Organization (1983) clinical trial verified these results, finding the discontinuation rates for amenorrhoea at 12 months and at 24 months to be significantly greater with DMPA than with NET-EN given on a 60 day regimen and for NET-EN given for 60 days for six months and then every 84 days. By contrast,Salem et al (1988) found that, even though amenorrhoea was more commonly experienced by DMPA users than by NET-EN (given every 8 weeks) users,the rate of discontinuation for amenorrhoea amongst NET-EN users was higher than amongst the DMP A users. The findings on discontinuation due to
amenorrhoea for NET -EN users from Banerjeeet al's(1984) comparative study of different dosages of NET-EN (Table 1.1.4 below) were similar to the findings for NET- EN discontinuation reported in the World Health Organization (1983) study.
Salemet al (1988) found that the second most common reason for method
discontinuation was"bleeding irregularities" with rates for DMP A found to be lower than for NET-EN (8.1 and 12.5 per 100 women respectively). The discontinuation rate for DMPA (Salemet al,1988) was less than the rates found in the World Health
Organization comparative trials (1977;1983). Rhamanet al (1985) reported that the most common reasons for discontinuing NET-EN were bleeding disturbances with heavy and/or prolonged bleeding being the single most frequent reason with a discontinuation rate of6.3 per 100 women. The discontinuation rate at 12 months for amenorrhoea was found to be somewhat less at 5.1 per 100 women (Rhamanet al, 1985),and this is also less than the findings from the World Health Organization (1983) study which found the discontinuation rate for amenorrhoea at 12 months,amongst NET-EN users on the same dosage regimen, to be 8.4 per 100 women (Table 1.1.4 below).
Benagiano and Primerio's (1983b) analysis of the 1978 World Health Organization study suggests that increased bleeding and amenorrhoea are more likely to lead to
discontinuation of injectables than spotting, decreased flow and irregularity of menstrual cycles. These authors submit therefore that bleeding patterns produced by NET-EN may be more acceptable than those resulting from DMP A use. On the other hand, Datey,et al (1995), in an analysis of clinical trials carried out by the Indian Council of Medical Research from 1981 to 1987, found that women experiencing frequent or prolonged bleeding were more likely to discontinue contraceptive use than those having delayed bleeding episodes or oligomenorrhoea.
Other Side Effects Leading to Discontinuation
Other reasons for discontinuation commonly reported in the World Health Organization (1983) trial were abdominal distention and weight gain, once again more frequently given as reasons for discontinuation by DMP A users, but not statistically different. Salemet al (1988) reported that weight gain, which occurred in both DMPA and NET-EN users was welcomed by the Egyptian women who participated in the study, particularly those living in rural areas. Other side effects given as reasons for discontinuation amongst South Africa users in the study by Beksinskaet al (2001a) were: weight change (increase and decrease), headache, vaginal discharge, skin problems, breast tenderness and dizziness.
1.1.5.3 Other Factors Influencing Discontinuation ofDMPA and NET-EN DoseofDMPA
Ina WHO multi-centre Phase III comparative clinical trial ofDMPA 100mg given every three months versus 150mg given every three months found that users of the higher dose (150mg) of DMPA were significantly more likely to discontinue use of the method than
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those using the lower dose (100mg) preparation (World Health Organization, 1986). Of note is the comparison drawn by the authors ofthe publication of this study (World Health Organization, 1986) who observe that the discontinuation rate for amenorrhoea of7.2%
found with the 100mg group is similar to the rate for NET-EN users (6.8%) previously reported in a comparative trial ofDMPA and NET-EN (World Health Organization, 1983).
Provider Influence and Attitudes towards Bleeding Irregularities
Meade et al (1984) conducted a phase IV prospective clinical study of NET-EN, given every two months,in rural Mexico in the late 1970s. They reported higher discontinuation rates with NET-EN (57.0 per 100 women) than reported in the WHO Phase III Clinical Trial (World Health Organization, 1983,49.7 per 100 women),but point out that the Mexico study findings are similar to those reported for the Mexico City centre participating in the WHO study (53.1 per 100 women).These authors found further differences with the World Health Organization (1983) trial,in that discontinuation rates due to amenorrhoea were higher and those due to bleeding problems to be lower than the World Health Organization (1983) study. They suggested that these differences could be attributed to different attitudes toward bleeding irregularities; different counselling by health workers on provision of the method; or different drug effects amongst users of different ethnicity (Meade et al, 1984). They point to the marked inter-centre variation found in discontinuation rates which characterize phase III studies of Il'Cs. Paul et al (1997) also draw attention to the marked inter-centre variability in study continuation rates and suggest that cultural differences may be an important influence on continuation patterns. Rahman et al (1985) also commented on the inter-clinic variation in discontinuation patterns of NET-EN in their Bangladesh study and attribute this variability to differences in staff attitudes and
counselling approaches.
More recently, a prospective study of 430 DMP A users was undertaken to determine factors influencing continuation rates (Hubacheret al,2000). The continuation rate at one year was 51%.Consistent with the findings above, providers were found to have an important influence on continuation rates, with women counselled to return to the clinic if they experienced side effects 2.7 times more likely to continue with the method.Those told that amenorrhoea might occur with injectable use were more than 2.5 times more likely to continue. Other factors found to be influential were number of children,attitudes towards menstruation,lactating on admission and spousal input on method choice.
Study Population
Paul et al (1997) report on a national population-based retrospective study of 1864 women in New Zealand. They submit that most studies undertaken on DMPA use have been among clinic attenders or women recruited into clinical trials,including the studies conducted by the WHO, and are therefore less likely to be representative ofDMPA users. In comparing DMPA continuation rates from their study with other studies, rates were found to be"as short or shorter". For instance, continuation rates at one year for first-time users was only 49% in the population-based New Zealand study,compared to 69% in the clinic-based Egypt study (Salemet al 1988).