ELSEVIER

Depot Medroxyprogesterone Acetate Patterns of Use and Reasons for Discontinuation Charlotte Paul,* David C.G. Skegg,* and Sheila Williams*

Little information is available from outside clinic settings about the acceptability of depot medroxyprogesterone ac- etate (DMPA, Depo-Provera@) as an injectable contracep- tive. In this national, population-based study, New Zea- land women aged 25 to 54 years were selected at random from voter rolls. The 1864 subjects were interviewed by telephone after an initial approach by letter. More than 1 in 8 women (13.7%) had used DMPA at some time. The proportion was higher among Maori women and among those of lower income and education, but DMPA had been used by a substantial proportion of all socioeconomic groups. A quarter of all users reported receiving only a single injection of DMPA, and only 53% had used this method for a total of 12 months or more. Only 5 (1.6%) of discontinuations were attributed to contraceptive failure; this corresponds to a contraceptive failure rate of 0.9 per 100 woman-years. Side effects were given as the most common reasons for stopping, with menstrual distur- bances and weight gain being cited most often. Other reasons for stopping included no further need for contra- ception or doubts about the appropriateness of DMPA. In this developed country population, DMPA is widely used for short periods but its acceptability is limited by the occurrence of side effects. CONTRACEPTION 1997;56: 209-214 0 1997 Elsevier Science Inc. All rights reserved.

KEY WORDS: depot medroxyprogesterone acetate, contracep- tion, side effects

Introduction

D epot medroxyprogesterone acetate (DMPA, Depo-Provera@) has been approved for use as a contraceptive in more than 100 countries

since the early 196Os,’ although its use has been dogged by controversy. A new era for injectable con- traceptives has been forecast following the publica- tion of reassuring evidence about the safety of DMPA,

* Department of Preventive and Social Medicine, Unrversity of Otago Medical School, Dunedin, New Zealand

Name and address for correspondence: Charlotte Paul, Associate Professor of Epidemroiogy, Department of Preventive and Social Medicine, University of Otago Medical School, P. 0. Box 913, Dunedin, New Zealand, Tel: +64-3.479. 7201; Fax: +64-3-479-7298

Submitted for publicatton May 16, 1997 Revised July 8, 1997 Accepted for publicatton July 8, 1997

@ 1997 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010

approval of DMPA as a contraceptive by the United States Food and Drug Administration (FDA] in 1992, and the introduction of new monthly injectables.’ Advice for providers and users is based on limited published experience of using DMPA, especially in developed countries. New Zealand has had a compar- atively high prevalence of use of DMPA since the contraceptive was licensed there in 1969.2

Side effects, particularly related to the disruption of the usual menstrual bleeding pattern, are common with DMPA. But apart from the context of clinical trials,3-5 little is known about the role of side effects in the decision to discontinue DMPA use.

We describe here the patterns of use of DMPA and reasons for discontinuation among a national random sample of women aged 2.5 to 54 years. These women formed the control group in a national case-control study of hormonal contraception and breast cancer risk.6,7

Subjects and Methods Voter registration is compulsory in New Zealand. Women were randomly selected from the voter rolls. Women whose telephone numbers could be found were eligible for inclusion. Over all ages, 78.3% of selected women had a telephone number identified. We wrote to the selected women re- questing information about their age and seeking their participation. Those who did not reply were telephoned. All subjects were written to between November 1, 1983 and October 3 1, 1987. We in- cluded women aged 25 to 54 years on a reference date (6 months before the date of interview); how- ever, we randomly excluded half of the potential control subjects under age 35 to better approximate the age distribution of cases in the case-control study. Interviews were completed with 84% of potentially eligible women; 10% refused to take part, and the remaining women were untraceable [3% j, were absent overseas (1 %), had English lan- guage difficulties [ 1%), or were either too ill or deceased (1%).

Women were interviewed by telephone. The inter- view sought details of medical, social, menstrual and

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210 Paul et al. Contraception 1997;56:209-214

Table 1. Characteristics of women who had ever used DMPA

Ever Used DMPA Percent Age-

Adjusted to 1986 Census Population

Yes No Percent Age 2.5 to 54 Years

Age group 25-34 years 55 350 13.6% 35-44 years 133 674 16.5% 45-54 years 64 588 9.8% All ages 252 1612 13.5% 13.7%

Ethnicity Maori 20 70 22.2% 23.9% Non-Maori 232 1542 13.1% 13.1%

Socioeconomic group l

Groups 1 and 2 24 236 9.2% 8.1%

Groups 3 and 4 135 939 12.6% 12.8%

Groups 5 and 6 90 417 17.8% 18.4%

‘Twenty-three women were excluded because they could not be classified by socioeconomic group.

reproductive histories. All interviews were conducted by one nurse interviewer or one of the authors (C.P.). To help recall of past contraceptive use, our initial letter was accompanied by a calendar on which women were asked to mark important dates such as marriages and births for reference during the inter- view. As a check on the interview method, we also wrote to the general practitioners of women who reported use of prescribed contraceptives in the pre- vious 5 years; there was close agreement between the contraceptive histories received from the general practitioners and from the women themselves. Thus, reports as to whether or not they had used DMPA in the 5 years before interview were in agreement for 249 of 253 women about whom information was obtained from physicians.’

Women were classified as users if they had received one or more injections of DMPA (in a few cases for noncontraceptive purposes). Each injection was as- sumed to equate to 3 months’ use, The continuation rate at 1 year was estimated by the proportion of first users who reported four or more injections. No other contraceptive injection had been available in New Zealand before the time of the study. Up to three reasons for stopping DMPA were recorded for each episode of DMPA use. Socioeconomic group was categorized according to occupation using the Elley- Irving scale.8 For married women, the occupation used was the higher of the woman and her husband.

Weighted percentages based on the 1986 census were calculated for Table 1 to take into account the

exclusion of half the women under age 35 in our sample. A previous comparison of the first 1000 women interviewed with the 198 1 census population showed that they were reasonably representative of the female population, although married women were overrepresented in our sample, and women who had no secondary education were underrepresented.

Results The characteristics of women who reported using DMPA are shown in Table 1. Overall, 13.7% of women aged 25 to 54 years reported using DMPA at some time (age-adjusted to the census population). Use was more common among Maori than non-Maori New Zealanders (who are predominantly European]. DMPA had been used by a substantial proportion of women in each socioeconomic group, but use in- creased with decreasing socioeconomic status. Among those with low income and education, the occurrence of use (18.4%) was about twice that of those with high income and education (8.1%).

Table 2 shows the timing and duration of use of DMPA. One quarter of all users reported receiving only a single injection of DMPA, and only 53% had used DMPA for a total of 12 months or more. Use before age 20 was rare in this population, and 74% of women first used DMPA at age 25 or older. The contraceptive was used mainly by parous women, with only 9% of women reporting use while nullipa- rous, and 73% of women had borne two or more children when they first used it. Most women (93%) reported only one episode of use, 5% reported two episodes, 2% three episodes, and none reported more than three. Hence, the patterns of duration of first and last use were similar to the total duration of use, except for use for 6 years or longer. For the most recent episode, the age at use was also similar to the age at first use, with 75% of women using DMPA at age 25 or older.

The total number of woman-years of use of DMPA among the 252 users was 542.2. The mean duration of use was 25.8 months and the median, 12 months. The mean number of injections was 8.7.

The reasons for discontinuation of DMPA for all episodes of use are shown in Table 3. Of all reasons for discontinuation, 5 (1.6%) were due to contracep- tive failure. This represents an estimated failure rate of 5/542.2 woman-years of use, or 0.9 per 100 woman- years. Only 27 discontinued DMPA because a preg- nancy was desired. For those women who said DMPA use was no longer required, the main reason was because of a sterilization operation (tubal ligation or vasectomy), hysterectomy, or natural menopause. Side effects were the most common reasons given for

Contraception 1997;56:209-214

Patterns of DMPA Use 211

Table 2. Timing and duration of use of DMPA

Number Percent

Total Use Duration of use

3 months 6 months 9 months 12-21 months 24-33 months 36-45 months 48-69 months 272 months Total

First use Age at first use

<20 years 20-24 years 25-29 years 30-34 years 235 years Total

Parity at first use Nulliparous One Two Three >Four Total

Duration of first use’ 3 months 6 months 9 months 12-21 months 24-33 months 36-45 months 48-69 months ~-72 months Total

Most recent use Age at most recent use

<20 years 20-24 years 25-29 years 30-34 years 235 years Total

Duration of most recent use* 3 months 6 months 9 months 12-21 months 24-33 months 36-45 months 48-69 months 272 months Total

66 26.2% 29 11.5% 23 9.1% 46 18.3% 23 9.1% 19 7.5% 16 6.3% 30 11.9%

252 100.0%

15 6.0% 50 19.8% 88 34.9% 48 19.0% 51 20.2%

252 100.0%

22 8.7% 45 17.9% 93 36.9% 50 19.8% 42 16.7%

252 100.0%

66 27.8% 32 13.5% 24 10.1% 48 20.3% 17 7.2% 16 6.8% 18 7.6% 16 6.8%

237 100.0%

13 5.2% 49 19.4% 86 34.1% 50 19.8% 54 21.4%

252 100.0%

68 28.9% 31 13.2% 22 9.4% 44 18.7% 19 8.1% 18 7.7% 16 6.8% 17 7.2%

235 100.0%

*Excluding 17 women who were current users at the reference date. tExcluding 15 women who were current users at the reference date,

stopping, accounting for 55% of all reasons. The most common side effects reported as reasons for stopping were menstrual disturbances, followed by weight

gain. Apart from the specific symptoms listed in Table 3, other symptoms given as reasons for stopping included headaches, tiredness, nausea, abdominal pain, breast enlargement, rash, nightmares, varicose veins, thrush, and acne. Five percent of reasons were doubts about the appropriateness of DMPA because of adverse publicity or concern that it was not “natural” as expressed by either the woman or her physician. Other reasons for stopping included the physician’s advice, age, an operation, completion of breastfeed- ing, and forgetting to attend for the next injection.

Table 4 gives the reasons for discontinuation of use for the most recent episode, according to the episode’s duration. The three contraceptive failures all oc- curred in women who had used DMPA for more than 3 months. The proportion of women stopping because DMPA was not required was higher with increasing duration of use. The occurrence of side effects as a reason for stopping was most important for short- term users. Symptoms were mentioned as a reason for discontinuation by 9 1% of users for 3 months, 73 % of users for 6 to 21 months, 53% of users for 2 to 5 years, and only 35% of users for 6 years or longer. There were no clear patterns for the individual symptoms, but amenorrhea was more commonly given as a reason for stopping in longer-term users and irregular bleeding in short-term users.

Discussion Whereas in many developed countries DMPA has been regarded mainly as an option for disadvantaged

Table 3. Reasons for discontinuation of DMPA for All Episodes of Use

Reason for Discontinuation Proportion of

Number All Reasons

Contraceptive failure-pregnancy

Pregnancy desired Not required

Not in sexual relationship Other reasons

Side effects Menstrual disturbances

Amenorrhoea Irregular bleeding Heavy bleeding

Weight gain Depression Loss of libido Raised blood pressure Other symptoms

Woman or physician concerned about appropriateness

Other Total number of reasons

5 1.6% 27 8.7%

23 7.4% 41 13.3%

63 20.4% 21 6.8% 21 6.8% 21 68% 37 12.0% 18 5,8%

2.3% ; 2.3%

36 11.7%

16 5.2% 29 9.4%

309 100.0%

212 Paul et al Contraception 1997;56:209-214

Table 4. For most recent episode of use,* reasons for discontinuation of DMPA according to duration of use

Reason for Discontinuation

3 months (N = 68)

No. %+

Duration of Most Recent Episode of Use

6-21 months 2-5 years (N = 97) (N = 53)

No. % No. %

~6 years (N = 17)

No. %

Contraceptive failure-pregnancy Pregnancy desired Not required

Not in sexual relationship Other reasons

Side effects Menstrual disturbances

Amenorrhea Irregular bleeding Heavy bleeding

Weight gain Depression Loss of libido Raised blood pressure Other symptoms

Woman or physician concerned about appropriateness

Other

0 2

2 9

26 6

13 7 9 8 4 0

38.2%] 28 (8.8%) 7

19.1%) 7 10.3%) 14 (14.4%)

9 8 1 0

13.2%) 16 (5.9%) 11.8%) 5 (5.9%) (5.9%) 2

(1.0%) 2 (3.8%) (5.9%) 15 (12.3%) 4 (7.5%) k (17.6%)

5 (4.1%) 3 6 (10.3%) 5

(2.9%) 1: (1.0%)

(13.4%)

(2.9%) 7 (7.2%) 13.2%) 15 (15.5%)

2 5 (17.6%

9 (17.6% 11 (35.5%

*Excluding 17 wornen who were current users at the reference date. tpercentages of all women who used DMPA for the specified duration.

women, in New Zealand there has been considerable use of this contraceptive in all social and ethnic groups. In this study population short-term use of DMPA was the norm, and few women chose to use DMPA again. Side effects were the most common reasons for stopping DMPA use. The injection was also shown to be an effective contraceptive, with an estimated failure rate of 0.9 per 100 woman-years.

DMPA use appears to be much less acceptable than is oral contraceptive use in this population, judging by the higher proportion of DMPA users reporting short durations of use. Of 1536 oral contraceptive users in the same population, only 406 (26%) had used oral contraceptives for less than two years,7 compared with 65% of DMPA users. This was not accounted for by the later marketing of DMPA, as even among younger birth control pill users (aged 25 to 34 years) only 20% had used oral contraceptives for less than two years.7

Our findings may give a more realistic picture of women’s perceptions of the risks and benefits of DMPA as a contraceptive than has been available from other studies, because of the nature of the population we studied. This national population- based study was undertaken after DMPA had been generally available in New Zealand for about 15 years and had been prescribed by a wide range of health care providers. Even recent studies of DMPA use in the United States9 and AustralialO have been of women attending specific clinics, as have the clinical trials

conducted by the World Health Organization (WHO].3f4 Such populations are likely to be much less representative of all DMPA users in the countries concerned. Although, in our study, information was collected retrospectively from the women, the re- ported timing of DMPA use showed close agreement with information collected from the latest prescriber. The data were collected from 1983 to 1987, before FDA approval of DMPA in the United States, and relate to use as far back as 1969. It is likely that FDA approval has changed clinician and patient attitudes toward injectable contraceptives in the United States, but because of the early licensing and widespread use of DMPA in New Zealand it is unlikely that there has been any major change in attitudes since the study was conducted.

Most women were parous at first use of DMPA and most first users were aged 25 or older. This pattern of use partly reflects the age group of our sample and the time period at which the information was collected. Although age and parity restrictions are now regarded as unnecessary,’ it is likely that DMPA use will continue to be favored by older women at the end of childbearing,5 when a delay in the return to fertility after use is unimportant. Nevertheless, special advan- tages of DMPA for teenagers have been described.” What information is available suggests that continu- ation rates and reasons for stopping in teenagers are similar to those in other age gr0ups.l’

Comparison of the duration of use of DMPA with

Contraception 1997;56:209-214

other studies suggests that durations of use of DMPA were as short or shorter in this population-based study. One-year continuation rates of 71.2%,12 48.3%,13 and 68.8%5 have been reported in clinical trials. Only 48.7% of first users in this survey contin- ued to 1 year. In the WHO multicenter trial,3t13 continuation rates varied markedly between centers, with low rates in Karachi, Lusaka, and Utrecht. Apparently, cultural differences are important in the decision to continue DMPA, and women in developed countries may be less tolerant of side effects, or they may simply have a wider choice of alternative con- traceptives available. A recent survey of first users from the United States reported a continuation rate at 1 year of 28.6%, ’ although this may represent the continuation rate past 1 year. The participants in that survey were mainly low-income women attending public clinics and one-third were nulliparous at first use, compared with only 8.7% in our survey. Another recent report from a private gynecological clinic in Australia showed apparently high continuation rates, with a mean number of injections of 6.3.” In fact, this is less than the mean number of injections (8.7) reported here. The mean number of injections is greatly affected by the number of long-term users, and is probably not a good indication of overall acceptabil- ity. The Australian study sample was also socioeco- nomically atypical; moreover, a substantial minority had been prescribed DMPA for treatment of medical conditions, and 40% of women were prescribed oral estrogens in the early months of treatment to control bleeding disturbances.

The most common reasons for stopping in our survey were side effects, and of these menstrual disturbances and weight gain were the most impor- tant. Menstrual disturbances were more likely among short-term users to be a reason for stopping, except in the case of amenorrhea. More detailed information collected prospectively in clinical trials suggests that prolonged bleeding and prolonged bleeding-free inter- vals are least acceptable and that frequent bleeding is better tolerated,9 although this may differ among cultures. We did not differentiate irregular bleeding with short or long bleeding-free intervals. Bleeding irregularities of any sort were reported as common reasons for stopping in recent clinic-based surveys.9,10 Weight gain has also been a common finding among DMPA users, although it has previously been sug- gested that few women discontinue use for this rea- son.’ Weight gain was also an important reason for stopping in the US study.9

About 5% of women in our sample reported stop- ping DMPA because of adverse publicity or nonspe- cific concerns about the drug expressed by the woman or her physician. The increase in knowledge about the

patterns of DMPA Use 213

long-term safety of DMPA’ should allow some of these concerns to be allayed. Improvement in patient consent procedures l4 should also ensure that women make an active decision to use DMPA.

Knowledge about side effects should lead to better counseling, advice, and information, which in turn should help women to select a contraceptive that is appropriate to their needs and concerns, and should improve continuation rates.15 A trial in China has demonstrated that pretreatment counseling can re- sult in a substantial increase in continuation rates.16 Nevertheless, our study adds to the finding among disadvantaged women in the US9 that the side effects of DMPA are not tolerated by a substantial number of women. Until better injectable contraceptives are available, work is needed to help delineate the char- acteristics of women who are likely to find DMPA suitable for their needs.

Acknowledgments This research was supported by grants from the Med- ical Research Council of New Zealand and from the Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization. We are grateful for the assis- tance of our interviewers Mrs. Celia Harris and Mrs. Janet Thomson, and also for the assistance of Mrs. Judith Smeijers and Mr. George Spears. We are grate- ful to the women who participated in the study.

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