CHAPTER 1.1 LITERATURE REVIEW AND OBJECTIVES
1.1.1 INJECTABLE CONTRACEPTIVE UTILISATION PATTERNS
The first injectable progestin was developed in 1953 and NET-EN was the first injectable contraceptive,developed in 1957 (Lande, 1995). MPA was first synthesized in the late 1950s (Babcock etai,1958) and the first clinical trials ofDMPA were conducted in 1963 (Weisberg, 1992). Johns Hopkins' Population Program's Population Report (Lande, 1995) provides a comprehensive international review of injectable contraceptive use up to the mid-1990s (Lande, 1995).According to this report, DMPA was available in more countries in the world than NET -EN. In general,injectable contraceptives were not a commonly used method except in South Africa,Indonesia, Thailand and New Zealand (Lande, 1995). The report, published in 1995, estimates that 12 million couples in developing countries used injectable contraceptives,and Bigrigget al (1999) reported that Depo Provera®has been used by more than 30 million women in the world since its introductionin 1963.
Although it has been widely available in the developing world since its introduction, DMPA was only approved for contraceptive use in the United States of America (USA) in 1992 (Weisberg, 1992). Since the USA Food and Drug Administration's(FDA)
approval of DMP A for contraceptive use, and the granting of a general license for DMP A
in the United Kingdom (UK) in 1995 (Cayley 1998), use ofDMPA has increased in countries in the developed world (Moore et al,1995;Bigrigg et al,1999 ;Margulies and Miller, 2001). For instance, Bigrigg et al (1999) report that the number of women in the UK using Depo-Provera" increased from 40000 in 1993 to 270000 in 1996. There also appears to be increasing popularity of injectable contraceptives among adolescents (American Health Consultants, 1994;Davis, 1996;Chotnopparatpattara and Taneepanichskul,2000;Margulies and Miller, 2001).
The Population Report (Lande, 1995) indicated that the ratio ofDMPA to NET-EN shipments by the United Nation'sPopulation Fund was 3:1,and stated further that donor agencies reported increasing orders for both progestogen-only injectable products in the 1990s.Use of injectable contraceptives by married women of reproductive age, based on survey findings from 1984 to 1994, as published in the Population Report (Lande, 1995) were found to vary widely from country to country. For instance,the percentage of contraceptive users using injectables in India (1992-1993) was reported to be 0%, and in Burundi (1987) to be 100%. Figures for South Africa (1987-1989) were reported to be 41%, the third highest usage rate of the 55 countries listed. The report does not
differentiate between DMPA and NET-EN use and figures providing this level of detail do not appear to be readily available in a comprehensive form.
A more recent account of worldwide contraceptive use amongst women married or in informal unions reports that injectable contraceptives were used by 4% of women in less developed countries and by 4%of women in Sub-Saharan Africa (Population Reference Bureau, 2002). This data sheet claimed to provide the most recent statistics on
contraceptive use globally, reporting on 138 countries in the developed and developing
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world. Itshould be noted that data on injectable use were not available for all countries included in the data sheet. The data are based on reproductive health surveys from 1990 onward, and injectable use amongst all women married or in informal unions in South Africa was reported to be higher (23%) than in any other country. The next highest rate of use was in Indonesia (21%), followed by Malawi and Thailand (16% each) and Peru (15%).
Use in the UK, New Zealand and the USA was reported to be quite low (2%, 2% and 1%
respectively).
According to Bongaarts and Johansson (2002) the contraceptive method mix is highly variable across regions and countries, with sterilization more prevalent in Asia and Latin America, and oral contraceptive (QC) and traditional method use more common in Africa.
They comment that in some countries a single method accounts for more than half of all use. The predominance of one method is ascribed to the emphasis placed on that method by providers, with little method choice offered to users (Bongaarts and Johansson, 2002).
As reported in the introductory chapter of this thesis, the widespread use of the injectable method among Black South African women was the focus of much criticism in the 1970s and 1980s. Nevertheless, post-apartheid, with a progressive national contraceptive policy in place (Department of Health, 2001), the method is still the most widely used contraceptive- - being used, according to the South Africa Demographic and Health Survey (SADHS), by 27% of all women aged 15-49 and by 30% of sexually active womerr' (Department of Healthet aI, 2002). As Bongaarts and Johansson (2002) found for certain countries in the
developing world, South African contraceptive use reflects a heavy reliance on one method, the injectable method,used by 54% of current contraceptive users in 1998 (Department of Healthet al,2002).
Although the contraceptive prevalence found in the SADHS was higher in urban than non- urban areas, injectable use was higher in non-urban areas (33% versus 28% amongst
sexually active women). Of the non-urban women using a modern method of contraception, 62%were using the injectable (Department of Healthetal,2002). Contraceptive prevalence in KwaZulu-Natal (KZN) was lower (58%) than the overall contraceptive prevalence (62%),and injectable contraceptives were used by 26% of sexually active women --lower than all but one other province (23% in Gauteng) (Department of Healthetal,2002). Just under half (46%) ofKZN women practicing contraception were using the injectable method. The SADHS does not provide statistics for urban and non-urban areas within provinces. The injectable method was particularly popular amongst younger South African users, used by 51% of 15-19 year old sexually active women (Department of Healthetal, 2002). This means that 80% of these young women who were using a modern method of contraception,were using the injectable.
The SADHS does not break:down injectable use according to whether DMP A or NET-EN was being used. Findings from other studies show that NET-EN is particularly popular amongst younger, nulliparous South African women (Woodet al, 1997; Beksinska et al, 1998;Beksinskaet al,2001a). However no studies have specifically explored the reasons for this pattern of use.Comparative data of this kind is not readily available in other
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countries of the world,perhaps because of the availability of only one injectable product in most countries.
After the injectable contraceptive, the next most commonly used methods were the oral contraceptive and female sterilization,used by 13.2% and 12% of sexually active women respectively (SADHS). The intrauterine device (IDD),male condom and male
sterilization were each used by 2% of sexually active women (Department of Healthet al, 2002). The SADHS also reports that condom use at last sexual act was 8%.
The injectable contraceptives currently available in South Africa are the progestogen-only preparations, depot medroxyprogesterone acetate (DMPA), registered as Depo-Provera'"
and the generic equivalent,Petogen", and norethisterone oenanthate (NET-EN) registered as Nur-Isterate®.DMPA was first used in South Africa in the late 1960s (Karstadt,1970;
Ferguson, 1974),and NET-EN became available in 1978 (Sapire, 1979).The product formulation, brand name, manufacturer and dosing schedule of each of these products is provided in Table 1.1.1. The same progestogen-only formulations are widely available across the world.According to Lande in a report published in 1995,DMPA was
registered in over 100 countries and NET -EN in over 60 countries worldwide. Combined injectable contraceptives (CICs), which contain a combination of oestrogen and
progestogen, are not yet registered for use in South Africa, but are widely available in other parts ofthe world,especially China and Latin America (Lande, 1995).
Table 1.1.1 Formulation, brand name, and dosing schedule of injectable contraceptives available in South Africa
Formulation Brand Name Manufacturer Dosing Schedule Progestogen-only:DMPA Depo-Provera Pharmacia& (a) Every 3 months 150mg depot medroxyprogesterone Upjohn (b) Every 12 weeks acetate
Progestogen-only:DMP A Petogen Intramed (a)Every 3 months
150mg depot medroxyprogesterone (b) Every 12 weeks
acetate
Progestogen-only: NET-EN Nur-Isterate Schering (a) Every 8 weeks for
200mg norethisterone oenanthate 24 weeks, then every
12 weeks thereafter (b) Every 8 weeks (a) According to the approved package insert (Pharmaciaand Upjohn,1993; Intramed,1993;Schenng, 1992) (b) According to the South African Medicines Formulary (Gibbon,2000)
Note: according to Lande (1995),the2-month schedule forNET-ENis recommendedby the World Health Organization
1.1.2 MECHANISM OF ACTION AND EFFICACY OF INJECTABLE